reza alizadeh-navaei

Anemia in cancer patients and following chemotherapy in affected patients is one of the factors affecting the health status and even the survival of patients, which should be evaluated. Considering the significant prevalence of cancer in Mazandaran province, this study was conducted to determine the incidence of anemia caused by chemotherapy and determine some factors related to it in patients with solid tumors in Imam Sari Hospital.

The current research is a cross-sectional study. The samples were selected from patients with solid tumors who were referred to the chemotherapy centers of Imam Sari Hospital in 2021 and 2022. The convenience sampling method was used. The inclusion criteria were patients over 18 years of age with solid tumors and the exclusion criteria were history of receiving blood in the last three months, radiotherapy, and anemia requiring treatment at the beginning of the study. CBC results of patients before and after chemotherapy cycles were recorded, and anemia was determined based on hemoglobin values. According to hemoglobin, the patients were classified into 4 categories: normal, mild anemia, moderate anemia, and severe anemia. Also, a decrease in hemoglobin (2 units or more) in the intervals between chemotherapy cycles was considered chemotherapy-induced anemia. In addition, information such as age, gender, type of cancer, and the type of chemotherapy regimen received were also recorded.

The total number of people who entered the study was 146, and the number of males was 91 (62.3%). The mean±standard deviation of the age of the participants was 56.8±12.7 years. Breast tumors in 56 people (38.4%), stomach in 48 people (32.9%), colorectal in 18 people (12.3%), and lung in 7 people (4.8%) were more than others. 51 people (34.9%) had Platinum-based chemotherapy, at first 39 people (26.7%) had normal hemoglobin, 80 people (54.8%) had mild anemia and 27 people (18.5%) had moderate anemia. 51.8% of patients with breast tumors, 22.2% of genitourinary tumors, and 8.8% of patients with gastrointestinal tumors had normal hemoglobin at the beginning of the study. The frequency of moderate anemia increased from 18.5% before chemotherapy to 36.1% after the third cycle of chemotherapy and 1.4 to 2.7% of patients developed severe anemia after different cycles of chemotherapy. 23 people (15.8 percent) of the examined patients had 2 or more units of hemoglobin drop after the first stage of chemotherapy, which happened in 10 people after the second stage (8.8 percent) and after the third cycle in 1 person (1.8 percent), it was observed. There was no significant relationship between 2 units or more hemoglobin drop with gender, age, tumor type, and type of chemotherapy regimen after the first cycle of chemotherapy (P<0.05).

The results of the present study showed that there was mild anemia in a large number of cancer patients, which increased after the first cycle of chemotherapy. Age, sex, type of tumor, and type of chemotherapy regimen had no significant relationship with hemoglobin drop in cancer patients undergoing chemotherapy.

Being Overweight is a global health problem and is related to important underlying diseases such as cardiovascular disease, malignancy, diabetes, fatty liver, etc. Over the past three decades, obesity has increased globally, especially in low-and middle-income countries. Numerous studies have shown that obesity increases the risk of developing chronic and threatening diseases including diabetes, cardiovascular diseases, blood pressure, and reduces life expectancy. On the other hand, chronic inflammation around fat cells plays an important role in obesity-related diseases. Also, changes in blood parameters are associated with increased body mass and chronic inflammation in obesity, and peripheral blood cells, such as the number of platelets, neutrophils, lymphocytes, and monocytes, are related to the progression of various types of diseases and inflammatory conditions. Therefore, the purpose of this study is to find the relationship between blood count biomarkers and anthropometric indicators in the adult group according to the Tabari cohort data.

Materials and methods:

 In the present study, cross-sectional data from a population-based cohort study called "Tabari Cohort Study" collected from 2014 to 2016 were used. This study is part of a nationwide study called "Epidemiological Prospective Study Group in Iran (Persian Cohort)". In the first phase of the Tabari cohort study, 10,255 participants aged between 35-70 years from urban and rural areas of Sari city were registered. Exclusion criteria in this study were inflammatory diseases, autoimmunity, malignancy, cardiovascular diseases, transplantation, and receiving any type of immunosuppressive drug, and finally 9939 people including 4043 men and 5896 women were included in the study. Age, height, weight, anthropometric measurements (BMI, waist circumference), CBC parameters including leukocytes, platelets, neutrophils, lymphocytes, and monocytes), and platelet distribution width (PDW) were recorded from the participants. By using the histogram drawing method to check whether the variables follow the normal distribution to decide between parametric or non-parametric analysis, T-test and ANOVA statistical tests, and SPSS 21 software, the results were extracted. The significance level in this study was considered to be 0.05 or less.

Waist-to-hip ratio was associated with higher WBC (P<0.001), platelet (P<0.001), and lymphocyte percentage (P<0.001). Higher waist-to-hip ratio was associated with higher WBC (P<0.001), platelet (P<0.001), lymphocyte percentage (P<0.001), and monocyte percentage (P<0.001). Higher BMI values were associated with higher WBC (P<0.001), platelet (P<0.001), lymphocyte (P<0.001) and monocyte (P<0.001) percentages. WBC, platelet, lymphocyte, and monocyte percentage were significantly higher in people who had a higher ratio of waist circumference to height (P<0.001).

The results showed that the relationship between anthropometric indicators and blood findings in favor of inflammatory conditions and obesity can affect indicators related to whole blood count.

COVID-19 is one of the biggest pathogens that mainly targets the human respiratory system. Among the preventive methods against contracting COVID-19, vaccination has had an important effect in preventing COVID-19 and is an essential component in prevention. Various vaccines were provided to prevent COVID-19, one of these vaccines was Sinopharm, which was used for cancer patients in Iran, so this study aimed to determine the antibody response following the injection of Sinopharm vaccine in cancer patients in Iran in 2021.

This cross-sectional study was conducted in 2021 on 74 patients with various types of cancers in Amol and Sari cities who received two doses of the Sinopharm vaccine. Subjects participated in the study after obtaining informed consent. Cancer patients who were referred to vaccination centers were asked to refer to the reference laboratory 4 to 6 weeks after the second dose if they wished to determine the antibody level. A 5 cc blood sample was taken 4-6 weeks after receiving the second dose of the vaccine, and then the serum was separated from the samples and stored at -20. The level of SARS-CoV-2 Neutralizing antibody, Anti-RBD, and Anti-Spike IgG were provided by Kit Eliza, Pishtaz Tab Company. The sensitivity and specificity of the kits used for neutralizing antibodies are 100% and 99% respectively, for Anti-RBD 98.4% and 97.7%, and Anti-Spike IgG 98.16% and 99.01% respectively. Finally, according to the instructions of the kit, neutralizing antibody values greater than 2.5 Mg/ml and optical absorption greater than 1.1 for RDB antibody and anti-spike antibody values greater than 8 RU/ml were considered positive.

The average age of the subjects was 57.1±11.7 years. In terms of gender distribution, 45 people (60.8%) were women. The neutralizing antibody status was positive in 41 people (55.4%). There was no significant relationship between the presence of neutralizing antibodies and gender (P=0.811) and age (P=0.443). Antibody against RDB antigen was positive in 31 people (41.9%). There was no significant relation between the presence of antibodies against RDB antigen with gender (P=0.091) and age (P=0.336). Antibody against Spike virus antigen was positive in 20 people (27%). A significant relationship was observed between the presence of antibodies against the Spike antigen and gender (P=0.008) and the proportion of women who produced antibodies against the Spike virus antigen was more than men, but there was no significant relationship between the presence of antibodies against the Spike gene and age (P=0.336).

The results of the present study showed that the vaccination of COVID-19 by Sinopharm in immunocompromised patients such as cancer patients can induce an antibody response, although the percentage is not high. Also, no significant relationship was observed between antibody production and age.

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant cancer treatment side effect that can influence both quality of life and treatment course. Melissa Officinalis (MO), due to its high content of flavonoids, has antioxidant, anti-inflammatory, and neuroprotective properties. 

The cancer patients diagnosed with CIPN attended a referral center in Sari (Iran). The hydroalcoholic extract of MO leaves was extracted by the maceration method. The control group received a placebo along with gabapentin as the standard treatment, and the intervention group received 500 mg Melissa officinalis 2 times daily for 3 months plus gabapentin. Patients were evaluated at the baseline and 3 months later, according to Common Terminology Criteria for Adverse Effects (CTCAE) and EORTC QLQ-C30 (Integrated System for Quality of Life Assessment). 

A total of 40 patients were considered as group D (intervention group), and 35 patients completed the study. Out of 40 subjects in the placebo group (P), 3 patients could not tolerate the drug due to gastrointestinal disturbances. The final values of CTCAE showed a statistically significant difference (p=0.010). Indicators related to the quality of life in both groups showed a significant improvement. In the intervention group, the pain perception and diarrhea experience were significantly reduced.

Quality of life indicators were improved by prescribing gabapentin with and without Melissa officinalis. The addition of Melissa officinalis to the chemotherapy regimen may improve diarrhea and pain perception.

According to previous reports, between 2%-5% of multiple sclerosis (MS) cases occur before the age of 16 years. 

This study aims to investigate the clinical and epidemiological features of MS in Iranian children to provide diagnostic criteria for policymakers and physicians.

This study objectives are achieved in two phases. The first phase was conducted and the second phase is underway. The first phase was performed in one year to design and finalize a pediatric MS registry software. For this reason, all variables and registration methods were determined. The second phase which has been started since 2016 consists of a routine data registry in the national phase. The project information, including all cases, epidemiological, clinical, and diagnostic factors is being reported based on different geographical areas of Iran.

We registered 932 cases with MS since 2017, of whom 74.4% were girls. There was no significant difference in mean age between girls and boys with MS (mean difference=0.73 years, P=0.133). Most of the children who were diagnosed were between the ages of 15 to 18 years (52.4%).

The registry for MS in children in Iran can improve the knowledge of health policymakers on the incidence of MS in children throughout the country, the first and most common symptoms of MS in children, raising physicians’ awareness about early diagnosis and treatment that consequently reduce the economic, psychological, and psychological burden of the disease.

Gastro-esophageal reflux disease (GERD) is a very common complaint. It is a major health concern and there is paucity of information about the epidemiology of the disease and its risk factors in Iran, especially Mazandaran province (North of Iran). This study aimed at investigating the prevalence of regurgitation and the factors associated with this condition in Tabari cohort study.

This was a cross-sectional study that analyzed data from Tabari cohort study. Information including the presence and frequency of heartburn and regurgitation, demographic characteristics, socioeconomic status, occupational history, history of chronic illnesses, history of alcohol and cigarette consumption were recorded.

The prevalence of GERD symptoms were 27.6% (20.4% in men, and 32.4% in women, p=0.0001). The frequency of typical symptoms was significantly higher in women than that in men. The risk of developing GERD symptoms were 1.7 times higher in women (p=0.0001). The highest prevalence of GERD symptoms was found in urban areas (41.8%, p=0.0001), in people with low educational levels (48%, p=0.0001), and in participants with history of depression symptoms (36.2%, p=0.0001). The prevalence of GERD symptoms was significantly high in individuals with higher BMI (29.5%, p=0.006), greater waist to hip ratio (29.1%, p=0.0001, p=0.0001), and high waist circumference (31.7%, p=0.0001).

This study showed gender, region of residence, educational level, and depression symptoms as the main risk factors for developing GERD symptoms.

The MUC1 gene encodes glycoproteins attached to cell membrane that play a protective role in gastric cancer and protect epithelial surfaces against external factors such as Helicobacter pylori. H. pylori infection can induce a cascade of innate and acquired immune responses in gastric mucosa. Relationship between rs4072037G>A polymorphism of MUC1 gene and increased susceptibility to H. pylori infection aimed to investigate in patients with gastric cancer in Mazandaran, northern Iran.

A case-control study was conducted on 99 patients with gastric cancer (H. pylori positive and negative) and 98 controls (H. pylori positive and negative) without gastric cancer (confirmed by pathological biopsy samples obtained during endoscopy). H. pylori infection was diagnosed by histological examination using Giemsa staining. Genomic DNA extracted from peripheral blood was analyzed by PCR-RFLP technique.

Analysis of all genetic models showed no significant relationship between rs4072037G>A polymorphism and risk of gastric cancer (GC). The relationship between H. pylori infection and rs4072037G>A polymorphism showed an increased susceptibility to gastric cancer in both positive and negative H. pylori groups (including case and control groups). The genetic model of GA/GG and H. pylori- positive versus GA/GG and H. pylori-negative showed a significantly increased susceptibility to gastric cancer (OR=0.251, CI: 0.128-0.493, P=0.000).

These findings indicate that rs4072037G>A polymorphism may interact with H. pylori infection to increase the risk of GC.

Breast cancer is one of the most common cancers among women. Abnormal expression of microRNAs is associated with cancer. Therefore, this study aimed to evaluate the expression of miRNA-210 in the serum of breast cancer patients.

The studied population included 49 breast cancer patients and 55 healthy individuals, and the samples were evaluated using Real Time PCR.

The data analysis of this study revealed that the expression level of miR-210 in the blood of breast cancer patients is significantly higher compared to the blood of healthy people. Also, there is a negative correlation between the age of breast cancer patients and the expression of miR-210 (r=-0.309, P=0.031) and a significant positive correlation between the increase in the expression of mir-210 and the expression of the Ki- 67 marker (r=0.412, P = 0.004).

Evaluation of miR-210 can be used as a diagnostic marker in breast cancer.

Leptin is an adipocyte-derived hormone with a critical role in energy balance. As demonstrated by previous investigations, leptin acts as a proliferative and angiogenic factor in cancer cells. However, results regarding its role in colorectal cancer are still inconclusive. We aimed to evaluate serum leptin and tissue expression of leptin receptor (Ob-R) in normal and malignant samples of colorectal.

Serum and tissue samples from pathology-confirmed colorectal cancer patients and normal controls referring to a university hospital of Mazandaran were obtained during 2019-21. ELISA and immunohistochemistry were applied to determine leptin and Ob-R expression respectively.

A total of 90 samples belonging to 46 normal and 44 CRC patients were enrolled. Normal and CRC groups included 32 (69.56%) and 21 (47.72%) female subjects respectively. The average leptin concentration in the normal group was 115.80 and, in the patient, group was 124.47 ng/mL (P=0.897). CRC cases showed an insignificantly higher Ob-R detection rate (P=0.086).

There was no significant difference in leptin and Ob-R expression between CRC patients and normal subjects. Thus, leptin and its receptor may not be useful as a biomarker of CRC.

Metabolic syndrome is a critical health concern associated with an elevated risk of chronic health problems including cardiovascular disease and diabetes. There are shreds of evidence that novel inflammatory ratios including neutrophil-to-lymphocyte, platelet-to-lymphocyte and lymphocyte-to-monocyte ratios serve as prognostic biomarkers for metabolic syndrome (MetS). This hypothesis was investigated in a cohort of the Iranian population.

selection of MetS + subjects was based on the National Cholesterol Education Program Adult Treatment Panel III criteria 3 (NCEP ATP 3). The control group consisted of participants negative for any of the five MetS criteria. Demographic and laboratory data were extracted from the Tabari cohort study.

A total of 1930 subjects including 965 Mets positive and 965 MetS criteria negative participants were evaluated. Diabetes (84.8%), hypertension (48.9%), hypertriglyceridemia (81.7%), low HDL cholesterol (70.3%), and high waist circumference (78.9%) were observed in patients. There were no differences between NLR (1.66±0.71 vs. 1.69±0.72 P=0.42), LMR (11.23±3.13 vs. 11.30±11.99, P= 0.86) and PLR (113.85±68.67 vs 114.11±35.85, P=0.91) between case and control groups, respectively. Logistic regression analysis revealed no association between ratios and MetS risk even after adjusting for potential confounders including age, gender, living place, and BMI.

In a relatively large population from Northern Iran, no association was observed between CBC-derived inflammatory ratios and the presence of MetS.

The diagnosis and treatment of cancer is stressful and perceived stress and concerns during the treatment period can add to this stress and affect the recovery of patients with gastrointestinal cancer. The aim of this study was to investigate the relationship between illness perception and coping styles, and perceived stress in patients with gastrointestinal cancer.

The present cross-sectional correlational study was conducted in 110 patients with gastrointestinal cancer in Sari Imam Khomeini Hospital, Iran 2022, selected by convenience sampling. Data were collected using a demographic questionnaire, The Brief Illness Perception Questionnaire (Brief IPQ), Billings and Moos Coping Styles Questionnaire, and Perceived Stress Scale (PSS). Finally, the data were analyzed applying descriptive statistics and Chi-square, independent t-test, Pearson's coefficient correlation, and ANOVA.

Most of the participants were females (50.9%), with a medium income level (59.1%), living in the city (91.8%), suffering from colon cancer (40.9%), and undergoing treatment (90.0%). Findings showed that most of the patients had a high level of perceived stress (57.3%), moderate levels of illness perception (71.8%), and moderate coping styles (71.8%). We observed an inverse relationship between perceived stress and illness perception (P<0.001, r=-0.604), but there were no significant relationships between perceived stress and coping styles (P=0.064, r=-0.177) and other demographic variables.

Considering the inverse relationship between illness perception and perceived stress, healthcare managers are suggested to take measures to improve the illness perception of patients with gastrointestinal cancer.

Breast cancer is one of the most common cancers and the first cause of cancer-related deaths in women. Evidence suggests that allergies may be associated with cancer progression. Immunoglobulin E as part of the allergic immune response plays a role in the occurrence of type 1 hypersensitivity responses and allergic diseases such as asthma, allergies, allergic rhinitis, and probably cancers.

We carried out a cross-sectional study in breast cancer patients as a case group and people without cancer as a control group. Total IgE level in the groups was measured by ELISA method using the monoset kit by Calbiotech (USA). Data, including total IgE level and eosinophil percentage of the patients along with participans’ age were recorded in excel. Data analysis was done in SPSS V19 using T-test, Mann-Whitney and partial correlation.

In this study, 160 patients were examined. The mean ages of patients in the case group and control group were 48.18±10.49 years and 41.68±7.95 years, respectively. There was a significant difference between the two groups in mean age (P<0.001). IgE level was not found to be significantly different between the two groups (P=0.92). Findings revealed no significant difference in eosinophil percentage between breast cancer patients and healthy patients (P=0.82). We observed no significant correlation between age and IgE levels (r=-0.043, P=0.594) and eosinophil percentage (r=0.145, P=0.068) after control for groups.

This study showed that the levels of IgE and the percentage of eosinophils in the peripheral blood cannot be not considered as a predictive factor in the diagnosis of breast cancer.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition that may require reduction or discontinuation of chemotherapy. Identifying effective methods in treatment of established CIPN requires determining the frequency of CIPN. There is a lack of comprehensive studies on this issue, so, this study was conducted to investigate the frequency of peripheral neuropathy caused by chemotherapy in cancer patients in Sari Imam Khomeini Hospital.

This longitudinal study was done in cancer patients receiving thalidomide derivatives, vinca alkaloids, taxanes, proteasome inhibitors, platinums, and microtubule destabilizers in Comprehensive Cancer Center at Sari Imam Khomeini Hospital (2021-2022). Neurotoxicity was assessed by the EORTC QLQ-CIPN20 questionnaire before the start of the chemotherapy cycle and three months later. Data analysis was carried out in SPSS by applying Mann-Whitney U test, t-test, and Chi-square.

The study included 103 patients. Fifty-four patients (52.4%) were younger than 55 years old and 49 (47.6%) were older than 55 years of age. Forty-nine patients (47.6%) developed chemotherapy-induced neuropathy in the three-month follow-up. Symptoms were more frequent in women, but were not significant (P=0.11). The average body mass index in patients who experienced neuropathy was higher than that in patients without neuropathy.

Almost half of the patients developed CIPN which raises the need for preventive training and interventions.

Recently, several studies have shown type 2 diabetes to be associated with gastric cancer and metformin appears to inhibit the growth of cancer cells by inducing apoptosis. This study was conducted to investigate the relationship between metformin and gastric cancer.

This case-control study included patients with gastric cancer (case group, n= 121) and a family member of patients with cancer (control group, n= 119). Diabetes history, duration and management of glucose level were recorded in a checklist and data were analyzed in SPSS applying T-test and Chi-square test. Also, logistic regression was used to calculate the odds ratio.

There were significant differences between the case group and control group in terms of age, gender, place of residence, level of education, BMI, and smoking (P<0.05). The adjusted odds ratio for history of diabetes was 0.87 (Adjusted OR=0.87, CI95%: 0.3-2.35) which was not significant (P=0.751). The study showed no significant difference between the two groups in history of diabetes control drugs (including metformin) (P>0.05).

According to current study, it appears that, in north of Iran, there is no association between gastric cancer and diabetes, control drugs (including metformin), and other factors such as duration of diabetes or a family history of diabetes.

Mature cystic teratoma of the ovary (MCTO) is the most common ovarian germ cell tumor. Its malignant transformation is a rare complication that occurs in almost 2% of the MCTs. MCTO is benign and usually appears between 30 and 40 years of age, but patients with malignant ovarian MCT are 10–15 years older than those with benign MCT. The most common malignant transformation in MCTO is Squamous Cell Carcinoma (SCC) which is rarely diagnosed with pre-operative imaging.We report the case of a postmenopausal woman, presenting with severe abdominal pain and a large palpable mass in her abdomen. She was diagnosed postoperatively with SCC arising from MCTO which was confirmed histopathologically. The patient received postoperative chemotherapy and was well at 6-month follow-up after chemotherapy.MCTO is benign, but can rarely become malignant in older ages. So MCTO-arising SCC should be considered in elderly women with abdominal pain and mass, and also some other evident features such as large tumor diameter, elevated serum markers, and solid components in Magnetic resonance imaging (MRI).

Burns are one of the most important health problems in communities. Traumatic injuries, especially Traumatic Brain Injury (TBI) associated with burns, may increase disability and mortality. In addition to preventing burns, any action for a better treatment approach and early detection of concomitant traumatic injuries can reduce complications, disability, and treatment costs. We aimed to investigate the outcome of children with burn injury with and without TBI.

In this cross-sectional study, 392 children with burn injuries treated at Motahari Hospital in Tehran, Iran from 2018-2019 were enrolled. Patient demographics, burn injury information and TBI-related information including head trauma and fracture were recorded in a checklist. Patients were divided into two groups of death (24 people) or discharge (368 people) in terms of outcome and the underlying variables were compared in the two groups.

There was no significant difference between the mean age of patients and gender in the two groups. The difference in the length of hospital stay, inhalation injury and skull fracture in the two groups was not statistically significant. The mean burn severity based on Total Body Surface Area (TBSA) and the frequency of TBI in the deceased group was significantly higher (P=0.001).

The severity of burns based on TBSA and TBI is associated with increased mortality among children with burn injuries. The results suggest the need to examine children with burn injuries for TBI using clinical examination or imaging.

Heart rate variability represents the performance of the cardiac autonomic nervous system (ANS) and is defined as the fluctuation of beat-to-beat between two successive R-waves (RR intervals). Accordingly, addressing the actions of the ANS in sickle cell disease helps in identifying the possible risk factors of sudden death. The clinical staging of the disease improves the diagnosis and the quality of the treatments.

This systematic review analyzed the data of the basal autonomic reactions in sickle cell anemia (SCA) and sickle cell trait (SCT) patients compared to healthy people. In this study, 441 articles were retrieved from PubMed, ProQuest, SCOPUS, Embase, and Web of Science databases. Some of them were removed based on the inclusion and exclusion criteria, and finally, seven articles remained for analysis.

The data analysis of the included studies demonstrated that the vagal modulation at the basal condition decreased in SCA or SCT patients compared to the control group.

The sympathovagal balance was altered in SCA or SCT patients, and an increasing trend was observed in sympathetic nerve activities.

Background and Clinical epidemiology of deceased COVID-19 patients is of great importance in identifying the risk factors for mortality and controlling the pandemic. In this study, we studied the demographic and clinical characteristics of deceased COVID-19 patients in Sari Fatemeh Zahra Hospital, Iran, between March 2020 and February 2021.
This retrospective cross-sectional study was performed by reviewing hospital records of deceased patients diagnosed with COVID-19 (n=214). Diagnosis of COVID-19 was confirmed on the basis of positive RT-PCR test and lung CT scan findings. Information about demographic and imaging characteristics, underlying diseases, and risk factors were collected. Data were analyzed in SPSS V25.
The mean age of deceased patients was 68.37 ± 14.1. The most common underlying diseases were hypertension(47.2%), cardiovascular disease (45.8%), and diabetes (40.7%). Abnormalities in lung imaging included peripheral lesions of ground glass in 149 (69.6%), ground glass with consolidation in 46 (21.4%), and crazy paving in 19 (9%) patients, respectively. There was no difference in mean age, sex, underlying diseases, and type of supportive care in patients who died during the epidemic waves of one to three.
Underlying diseases were the most critical risk factors for the death of patients with COVID-19 and should be given special attention in assessing the need for hospitalization and treatment of these patients. It is also recommended to conduct a comprehensive study of deceased patients before and after vaccination to evaluate the final effects of general immunization.

Several PI3K/Akt/mTOR pathway inhibitors and TLR agonists induce tumor cell death. However, the mechanisms of these therapeutic approaches in acute myeloid leukemia (AML) cells are still unknown. To investigate the effects of BEZ235, as a dual inhibitor of PI3K and mTOR pathways, and TLR7/8 agonist R848 on the expression and regulation of the immune inhibitory molecules in myeloid leukemia cells. WEHI-3 leukemia cells were incubated with dual PI3K and mTOR inhibitor BEZ235 and TLR7/8 agonist R848 for 48 hrs. Firstly, cell viability was assessed by MTT method. The semi-quantitative relative mRNA expression of Galectin-9 (Gal-9), PD-L1, PVR, and STAT3 was assessed according to HPRT as a housekeeping gene. Finally, the protein expression of phosphorylated STAT3 was evaluated by western blotting analysis. WEHI-3 cells showed growth inhibition following treatment with BEZ235 and R848 whose combination exerted more proliferation arrest. The mRNA expression of Gal-9, PD-L1 and PVR immune checkpoint molecules significantly reduced in treated cells with BEZ235 and R848. Combined treatment indicated more reduction compared with the single treatment. Finally, the expression and phosphorylation of STAT3 were down-regulated after a single or dual treatment with BEZ235 and R848. Our results conclude that treatment with the combination of BEZ235 and R848 interferes with immune evasion mechanisms through STAT3-signaling pathway in WEHI-3 leukemia cells.

There are controversies on the association between electrolytes and Coronavirus disease 2019 (COVID-19) and its severity. Studies on these issues may help in resolving ambiguities. The purpose of this study was to assess the association between electrolyte indices and being infected with COVID-19 and developing severe symptoms using a meta-analysis.

A thorough search was done in national and international electronic databases using Medical Subject Headings (MeSH) terms. Quality assessment was conducted by Newcastle-Ottawa scale (NOS) checklist. We estimated the standardized mean difference between electrolyte indices and the incident of COVID-19 infection and its severity.

After screening the papers, 12 met the inclusion criteria. According to the meta-analysis results, the standardized mean differences for serum level of sodium and potassium between the dead and survived COVID-19 patients was estimated to be 0.22 (95% CI: -0.03, 0.46) and 0.14 (95% CI: -0.22, 0.50), respectively. The standardized mean differences for serum levels of sodium, calcium, and potassium between patients with severe and non-severe COVID-19 were estimated to be -0.28 (95% CI: -0.72, 0.17), -1.07(95% CI: -1.58, -0.55), and -0.10 (95% CI: -0.47, 0.27), respectively.

In this meta-analysis, the standardized mean difference for calcium was significantly lower in severe COVID-19 patients compared to that in patients with mild and moderate forms of the disease.

One of the most critical and controversial issues regarding the pollution of water resources and agricultural products is the challenging relationship between nitrate intake and the risk of gastrointestinal cancers. During the last two centuries, human activities have fundamentally changed the global nitrogen cycle and increased the amount of nitrate in the soil. Nitrate and nitrite move quickly in the environment due to the high solubility. Nitrate in wastewater or fertilizers used to increase crop production can be accessed to surface and groundwater by rainfall or irrigation. Nitrate in the diet is absorbed into the bloodstream and enters the oral fluid through the salivary glands. Approximately 25% of nitrate in the human body enters the salivary glands after absorption in the upper gastrointestinal tract, and it is actively concentrated up to 20 times in saliva. Nitrite disrupts young vertebrates by destroying hemoglobin in the blood and forming the toxic compound methemoglobin. Nitrite also causes hypotension (reduction of arterial pressure), a precursor to the formation of carcinogenic nitrosamines. However, there is no conclusive evidence that nitrate can cause cancer without amines containing nitrosamines.Since accurate information about the amount of nitrate in drinking water sources and vegetables used in Mazandaran province is not available, this study aimed to obtain accurate and up-to-date data on nitrate concentration in drinking water and vegetables. Also, the relationship between nitrate concentration in drinking water and vegetables in areas of Mazandaran province with a high and low prevalence of gastrointestinal cancers was investigated.

In this study, two areas with high incidence and low incidence of gastrointestinal cancers (Savadkuh and Simorgh counties, respectively) were identified. Information on patients with gastrointestinal cancer was prepared between 2014-2016. Then the patients living in the studied counties were separated and coded. Nitrate concentration in 30 samples of vegetables (60 samples in total) and water was analyzed by spectrophotometry and compared with international standards.The selection of vegetable samples was made according to the prevailing consumption pattern of the people. Selected vegetables included tomatoes, lettuce, potatoes, onions, cucumbers, garlic, cress, and spinach. According to the available instructions, plant samples from each region were quickly transferred to the laboratory. Nitrate concentration was measured by the semi-micro distillation method. The relationship between nitrate concentration and the incidence of gastrointestinal cancer and the ASR index of gastrointestinal cancer were determined using SPSS (26) software for Mazandaran province.Discussion of

Statistical analysis of the data showed that nitrate concentration of all studied crops in the Savadkooh region showed a significant difference compared to the Simorgh region, except potato. In the Simorgh region, nitrate concentration in lettuce, cress, potato, and spinach was lower than the maximum limit, while other vegetables were significantly higher than the standard. The data showed that in Savadkuh and Simorgh regions, the highest nitrate concentration was observed in garlic and the lowest in onion. According to the data, except for potatoes, all other vegetables in the Savadkooh region were significantly higher than the Simorgh region (p <0.01). The average concentration of nitrate in the drinking water of Savadkooh and Simorgh counties was significantly lower than the standards presented in the literature.The effect of nitrate concentration variables (in the regression model presented) in tomatoes, potato and cucumber, and drinking water was more than the allowable error (0.05). Therefore, changes in the nitrate concentration of these products and the amount of nitrate in drinking water will not significantly affect changing the dependent variable (the incidence of cancer). On the other hand, the significance level of the t-test for the effect of nitrate concentration variables in spinach, garlic, cress, and onion was less than the allowable error (0.01). Therefore, changes in the amount of nitrate in these variables significantly affect changes in the dependent variable. Based on the coefficients related to β, the most effect on the changes of the dependent variable will be the change in the amount of nitrate in spinach and garlic with a coefficient of β of 0.372 and 0.367, respectively. The amount of nitrate in the variables of cress and onion are of the following ranks. Comparison of residual nitrate levels in vegetables in Savadkuh and Simorgh showed that nitrate levels in Simorgh city were lower than Savadkuh, and nitrate concentration in four vegetables i.e. lettuce, cress, onion, and spinach, was less than the maximum limit. However, other products far exceeded the maximum limit. According to the researchers of the Razi University of Kermanshah, the concentration of nitrate in all cases under investigation in Kermanshah was exceeded by the National Standard Institute of Iran. The highest and lowest nitrate concentrations were observed in the Savadkuh region with an average of 3398 and 71 mg/kg in garlic and onion crops, respectively, and in the Simorgh region with an average of 2259 and 38 mg/kg in garlic and potato as well. The common denominator between the two regions is the lowest nitrate concentration observed in the onion crop. Significant differences between the two counties in terms of nitrate concentration in the studied products, except potato, can be examined from various aspects. It seems that the management of fertilizer consumption, especially nitrogen fertilizers in the Simorgh region, has been done better. The result has been shown by reducing nitrate accumulation in agricultural products of the region. Nitrogen in chemical and organic fertilizers is converted to nitrate after use in soil by soil bacteria such as Nitrosomonas and Nitrobacter. Nitrate absorbed in the root is reduced and converted to ammonium compounds and transferred through the vascular system to different parts of the plant, and used in physiological processes of the plant. Suppose the amount of soil nitrate increases for any reason, including excessive consumption of nitrogen fertilizers, and the plant does not have the necessary ability to reduce it. This compound enters the plant organs through the mass transfer mechanism and the vascular system and accumulates there.It has been found that there is a direct relationship between the concentration of nitrate in the environment and the amount of nitrate accumulation in agricultural and horticultural products, so that the most important environmental factor affecting the accumulation of nitrate in the product is the amount of available nitrate ions. In addition, harvest time (morning or evening) is also an essential factor in the amount of nitrate output through the harvested product. Receiving light energy during the day increases the plant's photosynthesis, and the production of more assimilates and increases the activity of the enzyme nitrate reductase in the plant. The average nitrate concentration in drinking water was 10.4 mg/L in Savadkuh and 15.8 mg/L in Simorgh. Fortunately, this concentration is lower than the standard defined for drinking water (50 mg/L) in both areas.

Although the concentration of nitrate in the drinking water of Savadkuh county is significantly higher than Simorgh one, the concentration of nitrate in the drinking water of both counties is below the standard limit. Therefore, there is probably no significant relationship between the prevalence of gastrointestinal cancers and nitrate concentration in drinking water sources in these areas.Nitrate concentration in vegetables consumed by patients with gastrointestinal cancers in the Savadkuh region was significantly higher than the Simorgh region and, to some extent, maximum contaminant level. The results showed that the consumption of spinach, garlic, cress, and onion had played an influential role in increasing the incidence of gastrointestinal cancers. Therefore, management practices in agriculture, especially changes in the consumption pattern of nitrogen fertilizers, are inevitable to reduce the accumulation of nitrate in vegetables. It is strongly recommended that the vegetables be harvested in the afternoon to reduce nitrate accumulation in the plant tissues. It is suggested that new strategies to reduce nitrate accumulation in food, especially vegetables, be studied to reduce the incidence of gastrointestinal cancers in this province.

 Due to a lack of data on pediatric multiple sclerosis (MS) epidemiology in Iran, this study aimed to determine the incidence rate of pediatric MS in Iran.

 All the data of the patients with MS registered in the Ministry of Health and Medical Education of Iran for 20 years were collected in this study; therefor; those born in 1982 and diagnosed with the disease and treated since 2000 were included in this study. The collected variables were patients’ age at the time of diagnosis, gender, year of diagnosis, urban or rural residency, and province of residence. Additionally, age- specific incidence rates per 100,000 of the population were calculated.

This study was performed on 4544 cases of pediatric MS within 2000- 2019, of which 997 patients (21.9%) were male. The mean age of the patients with MS at the time of diagnosis was 14.3±4.6 years, and 4414 children (97.1%) lived in urban areas. The incidence rate of pediatric MS in Iran during 20 years increased from 0.26 per 100,000 of the population in 2000 to 1.53 in 2019.

 The incidence of pediatric MS in Iran is high, and the development of diagnostic practices in the past decade in Iran has contributed to the detection of this high incidence

Frizzled receptors (FZD) play a pivotal role in the initiation and progression of a wide array of cancers. Dysregulated expression of FZD receptors is correlated with higher metastasis and invasive potential, as well as short survival in many malignancies. In this meta-analysis, we aimed to verify the prognostic value of FZD receptor expression on patients’ survival with different types of gastrointestinal (GI) cancers, including gastric, colorectal, and esophageal cancers.

A systematic search was performed using PubMed, Scopus, and Web of Science from 2000 to November 2020. Fourteen studies, including 2997 patients met our inclusion criteria, in which nine articles were considered FZD7 while the rest were about other FZD members. The fixed-effect model was used to estimate the pooled hazard ratio (HR) and the 5-year overall survival (OS) rate. We used the Newcastle-Ottawa scale of cohort articles to determine the quality of included studies.

The results showed that high expression of FZD receptors is associated with the poor survival in patients with GI cancers (HR= 1.83, 95% CI: 1.5–2.17). Moreover, multivariate analysis indicated that FZD receptors could be considered as an independent prognostic factor (HR = 1.76, 95% CI: 1.37–2.16).

According to our results, overexpression of FZD receptors predicts a poor prognosis in patients with GI cancers and could be used as a useful therapeutic target.

According to previous studies, using the frozen section procedure during breast surgery reduces the rate of error and the need for re-surgery. We aimed at performing a comprehensive systematic review and meta-analysis to provide reliable evidence on the diagnostic value of frozen section procedures in breast-conserving surgery (BCS).

A thorough search was performed in PubMed, Embase, Cochrane Library, and Web of Science databases for human diagnostic studies that used the frozen section in BCS. Meta-analyses were done to find the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR).

Human diagnostic studies used the frozen section in breast-conserving surgery and studies that reported the sensitivity and specificity of the frozen section in BCS or contained data that could be calculated the desired parameters were selected for this meta-analysis.

Assessment of studies quality was done and data was extracted from included papers. Then, the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to assess the quality of included papers.

Thirty-five papers were entered into our study. The meta-analysis indicated the high sensitivity (83.47, 95%CI 79.61 - 87.32) and specificity (99.29, 95%CI 98.89 - 99.68) for the frozen section in BCS, which resulted in an accuracy of 93.77 (95%CI 92.45 - 95.10). We also found a significant PPV (93.26, 95%CI 91.25 - 95.27), NPV (92.17, 95%CI 90.22 - 94.11), PLR (7.99, 95%CI 6.01 - 9.96), and NLR (0.18, 95%CI 0.14 - 0.23).

The findings showed that intraoperative frozen section analysis has high sensitivity and specificity for evaluating lumpectomy margins in patients with early-stage breast cancer and significantly reduces the need for re-operation. Accordingly, re-operation costs are not imposed on the patient and reduce the anxiety of the patients.

Given the nature of the dental profession and the tools and equipment used and direct contact with saliva and mucous membranes, it is crucial to observe all cases of infection control. Due to the high prevalence and risks of coronavirus, and its novelty and sensitivity of the dental work, the present study was conducted to investigate the observance frequency of requirements for providing dental services during COVID-19 epidemic in the dental offices of Sari, Iran. In the present study, 181 dentists, including 147 general dentists and 34 dental specialists in Sari, were surveyed. To collect data, the checklist of Ministry of Health, Treatment and Medical Education was used. It included questions about the use of rubber dam, high-pressure suction, proper ventilation, air disinfection device, screening and triage of clients, and so on. After completing the checklist and scoring, the data were statistically analyzed.Descriptive statistics (frequency analysis) and Chi-square test were used to analyze the data. Statistical significant level was considered at P < 0.05. The highest observance frequency of the requirements was related to Requirement 14 (observing the distance between clients' chairs) with frequency of 97.2%, followed by Requirement 2 (the use of high-pressure suction), Requirement 7 (package of separate sterile disposable devices for each patient), and Requirement 15 (removal of all common devices in the waiting room), with frequency of 97.0%. The highest observance frequency of preferences was related to Preference 4 (the use of one-way valves in the unit) with frequency of 96.7%. Regarding employment history, dentists with more than 15 years of employment history observed only the item of waste disposal items in accordance with the health protocol significantly more than dentists with less employment history (P = 0.04). In general, most dentists who participated in this study observed the health protocols at good level. Dental specialists observed most of the requirements more than general dentists.