مجله دانشگاه علوم پزشکی مازندران
پیاپی 207 (فروردین 1401)

In recent years, immunotherapy using chimeric antigen receptor T cells (CAR T cells) has been considered as a novel and promising treatment for some diseases, especially cancer. The CAR T cell production is a multi-step, complex, time-consuming, and costly process. One of the most important steps in production of CAR T cells is expansion of these cells at appropriate numbers for injection. Therefore, the aim of this study was to investigate the methods of expansion for human CAR T cells in ex vivo.

In this study, specifically engineered CAR T cells against the MUC1 tumor antigen were prepared. The cells were then treated with rIL-2, anti-CD3/C28 Dynadeads, and allogeneic PBMC (Rapid expansion protocol (REP)) for 14 days.

The results showed that using anti-CD3/CD28 antibodies in effective ratios; 1: 1 and 1: 3 (bead: cell) along with (IU100) rIL-2 resulted in a 27.5-fold increase in the number of cells. However, the use of rIL-2 alone or allogeneic PBMC eventually resulted in 4.5-fold increase and 9-fold increase, respectively.

Anti-CD3/CD28 in combination with rIL-2 can provide all three signals required for T cell activation and proliferation which can be a suitable alternative to costly and expensive cell proliferation techniques for animal or human CAR T cell studies.

MicroRNA-122 (miR-122) is the most abundant liver–specific miRNA. It has been reported that miR-122 plays several biological roles such as iron homeostasis, tumor suppressor, hepatic fatty acid regulation, and in hepatocyte differentiation. The Purpose of this study was to investigate changes in liver miR-122 gene expression and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes after resistance training and boldenone undecylenate (boldenone) steroid injection in male rats.

Twenty male Wistar rats were randomly divided into four groups: control (n=5), resistance training (n=5), resistance training+ boldenone injection (n=5), and boldenone injection (n=5). Resistance training was performed three sessions a week for eight weeks. Boldenone was injected twice per week (2mg/kg). Seventy-two hours after last training, blood and tissue samples were collected. Serum levels of ALT and AST were measured via photometric method and miR-122 gene expression in the liver was assessed by real-time PCR. Statistical analysis was conducted using SPSS V16.

Reduced expression of liver miR-122 was found in boldenone group, while the expression of miR-122 was higher in resistance training group, however, the difference was not significant (P= 0.514). Also, no significant difference was found in serum AST and ALT levels between the experimental groups (P= 1.00 and P= 0.527, respectively).

In this study, liver miR-122 responded differently to resistance training and boldenone injection. However, clear understanding of its mechanism requires further studies.

The harmful effects of morphine on the liver after withdrawal syndrome are unclear. In this experiment, we investigated the effects of exercise on oxidative stress, liver inflammation, liver enzymes, and liver histology after morphine withdrawal in rats.

In this experimental study, male Wistar rats (n=30) were randomly divided into five groups: ‎‎control, withdrawal syndrome (addicted), withdrawal syndrome+‎endurance training, withdrawal syndrome+‎resistance training, withdrawal syndrome+concurrent training. The experimental groups received morphine for 28 days, and after withdrawal, training interventions were done for 10 weeks. At the end of the study, the rats were sacrificed and liver was removed. Antioxidant activity ‎was measured and histopathological evaluation of ‎liver was done. Also, the TNF-α levels were determined.‎

Compared with control rats, the levels of total antioxidant capacity (TAC), and the activities of glutathione and superoxide dismutase (SOD) significantly decreased in morphine withdrawal group (P<0.05), while malondialdehyde (MDA) concentration, total oxidant capacity (TOS), and TNFα significantly increased in this group (P<0.05). However, training interventions reduced the concentration of MDA, TOS activity, and TNF-α and increased TAC, SOD, and glutathione. Histological analysis indicated major changes in addict group, while training alleviated these changes.

Morphine is used as analgesic in patients, but this study showed that it has harmful effects on liver function and histology.

Background and Major depressive disorder (MDD) is a massive challenge for community mental health. Serum zinc and cortisol are suitable biomarkers for assessing the response to a given treatment. In the present study, serum concentrations of these markers were compared between two groups of patients treated with fluoxetine and cognitive behavioral therapy.
In this randomized clinical trial study, 40 female MDD (DSM-V criteria) patients were divided into two groups: fluoxetine therapy (20 mg/daily/3 months, n=20) and group CBT (90-min/once a week/12 weeks, n=20). Severity of depression was studied by Beck Depression Inventory (BDI-II) and serum cortisol and zinc concentrations were measured before and after treatments. Data were analyzed in Graphpad Prism 9.
BDI-II scores significantly reduced in both fluoxetine therapy (from 23.2±1.5 to
11.1± 1.1) and CBT (from 26.8±0.6 to 9.5±0.8) groups after treatments. Serum cortisol level did not change in patients treated with fluoxetine, but it decreased in CBT group (from 453 ± 0.09 to 386.4±0.07). Serum zinc level decreased in the fluoxetine group (from 91.6±4.8 to 72.8±2.8) and increased in the CBT group (from 78.9±2.1 to 86.5±2.6). Post intervention inter-group comparison showed greater decrease in BDI-II score and cortisol concentration in CBT group than the fluoxetine therapy group.
The decrease in BDI-II score and cortisol level and increase in serum zinc were higher in CBT group than fluoxetine group. Therefore, CBT seems to be suitable for treatment of MDD. Further studies are needed with larger sample size and longer study periods.

(Clinical Trials Registry Number: IRCT20190710044171N1)

Background and The association between periodontal diseases and endometrial cancer (EC) has been assessed in some studies but the probable role of inflammatory factors such as visfatin is unknown. This study aimed at evaluating the levels of visfatin in gingival crevicular fluid (GCF) in patients with EC and chronic periodontitis (CP) to address this gap.
In a case-control study with matched age and body mass index controls, 120 female participants were divided into four groups. Case groups included group I (EC-CP [n=20]), group II (EC without CP [n=20]), and controls were group III (without EC but diagnosed with CP [n=40]), and group IV (healthy without EC or CP [n=40]). GCF samples were collected and visfatin was assessed by enzyme-linked immunosorbent assay.
Clinical periodontal parameters such as periodontal pocket depth, clinical attachment loss, and bleeding on probing were significantly higher in EC-CP group than other groups (P<0.001). Mean visfatin level in GCF was found to be significantly different in group I compared with groups II and IV (P<0.001). Also, there was a significant difference in visfatin concentration in GCF between group III and group IV (P<0.001).
According to current study, GCF visfatin concentration is probably associated with EC and CP.

Background and Hospital Length of Stay (LoS) is a good indicator of the quality of hospital care. The purpose of this study was to identify the best standard models for survival analysis to determine the factors affecting the length of hospital stay in burn patients.
In this cross-sectional study, the hospital records of 460 burn patients hospitalized in Sari Shahid Zare Hospital, 2013-2019 were reviewed. Best model was introduced using Akaike information criterion (AIC) method. Multivariate survival analysis was done and factors affecting the LoS were determined. Statistical analyses were performed using R ver. 4.1.1 (survival package) and SPSS ver. 24.

The Burr parametric model had the lowest AIC value (3284.92) and was therefore selected as the best model. Comorbidities, including diabetes (HR= 1061, 95% CI: 0.28-0.67), location of accident (HR= 1.33, 95% CI: 0.07-0.49), burn percentage (HR=0.73, 95% CI: 0.28-2.35), and time interval between burn incidence and hospitalization (HR=1.69, 95% CI: 0.18-0.88) significantly affected the duration of hospitalization (P<0.05).


The Burr model fits better than other standard parametric models of survival analysis to determine the factors affecting the length of hospital stay in burn patients.

Background and Laryngeal cancers are associated with high rates of mortality and disability. No effective screening test is proven for this disease, so, the best way seems to be controlling the disease by identifying and eliminating individual predisposing factors. The aim of this study was to pave the way for a better understanding of the risk factors and factors affecting the type and prognosis of laryngeal lesions.
A cross-sectional study was performed using the records of patients who had a biopsy in Sari Bu Ali Hospital, between 2009 and 2019. Demographic and clinical information such as age, gender, clinical diagnosis, pathological diagnosis, location of recurrence, recurrent cases, and type of benign tumors were collected.
We studied 423 patients, including 331 (78.3%) males and 92 (21.7%) females, 254 (60%) lived in cities and 169 (40%) patients lived in rural areas. History of narcotics consumption, alcohol, and smoking were seen in 189 (44.6%), 136 (32%), and 312 (74%). respectively. In patients  with malignancies, the mean age at onset of disease decreased during the years of study, but in patients with benign lesions the average age of incidence of lesions has increased significantly (P<0.05). In this study, men were found to be at higher risk of developing non-malignant lesions than women.
These findings are a warning and should be considered in educational social and epidemiological programs for preventive measures.

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.

Medicinal plants are among highly consumed natural drugs. Many herb shops produce and sell this products without any license. Traditional herbal distillates are widely used in Iran, so, the aim of this study was to determine ethanol and methanol concentrations in handmade herbal distillates in Tehran herb shops.

A total of 140 samples from 14 traditional handmade herbal distillates were obtained from Tehran herb shops and analyzed using headspace gas chromatography.

In this study, no sample contained ethanol. Peppermint distillate had significantly higher methanol content (334.62±153 ppm) compared with other distillates (P<0.05). Also, high amounts of methanol were found in Fenugreek (321.43 ppm) and Tarragon (311.39 ppm) distillates. Pennyroyal distillate did not contain methanol and rose water had the lowest methanol content (14.61 ppm).

Handmade herbal distillates containing high concentrations of methanol can cause health problems in regular consumers. Therefore, highly consumed herbal distillates should be monitored to determine their methanol concentration.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system. The purpose of this study was to report the information of MS patients registered in Mazandaran MS Registry System between 2019 and 2021.

This retrospective study was performed in patients with MS living in Mazandaran province using the MS national registry system in Iran.

A total of 2211 patients were found, including 72.8% females and the mean age of patients was 36.97±9.47 years. Most of the patients had Relapsing remitting (RR) MS (61.2%) followed by Secondary progressive (SP) MS (19.6%) and a family history of the disease was seen in 16.2%. Most of the patients lived in populated cities; Sari and Amol. Interferons, Rituximab, and Fingolimod were found to be the most widely used drugs. The mean score for Expanded Disability Status Scale (EDSS) was higher in men than women. The mean EDSS scores were the lowest in clinically isolated syndrome (CIS) type of the disease and the highest in the SP and RP types. The level of disability was significantly higher in men than women (P<0.001).

The types of MS in Mazandaran province is similar to global data of this disease, but the increasing prevalence of familial MS in this province compared with other provinces requires more detailed studies.

World condition has changed since the Coronavirus disease 2019 (COVID-19) emerged and its rapid spread affected people’s social and sports life. In this study, we aimed at investigating the incidence of sports injuries in Mazandaran province, Iran and the effects of COVID- 19 pandemic on frequency of sports injuries. We also studied the relationship between sports injuries and age, gender, sports specialties and severity of injury.

In this descriptive-analytical study, information of all/injured athletes registered in Mazandaran Sport Medicine Center between 2018 and 2020 were analyzed in SPSS V23. In order to investigate the relationship between injured limb and age, gender, sports specialty, injured side, and surgery, Chi-square test was applied.

The numbers of registered athletes were 51.56, 50.59 and 16.45 per 10,000 population in the province and injured athletes included 6.90, 6.62, and 5.73 per 10,000 registered ones in 2018-2020, respectively. The majority of athletes were men. After the COVID-19 pandemic, the rate of injury was high in soccer (9.09 per 10,000 registered athletes), knee injuries increased to 40.8%, and surgery was performed in 23.3% of all injuries. Significant relationship was found between injured limb and age (P˂0.05) and sport specialty (P˂0.001) during the years studied.

Reduction in number of registered athletes and no considerable change in sports injuries indicate a decrease in recreational athletes after the outbreak of the COVID-19 pandemic. However, prohibition of indoor sports activities can be the reason for increase in men injuries, especially football players. Also, professional athletes experienced serious and more knee injuries

Asthma is a chronic inflammatory disorder of the airways caused by a combination of complex environmental and genetic interactions. There is an incomplete understanding of this mechanism which affect both severity of the disease and how it responds to treatment. Different gene expressions are reported in patients with asthma and healthy controls.

In this study, a common list of different genes expressed (DEG) was identified using bioinformatics methods. Three studies from microarray data that met the study’s inclusion criteria were selected. These studies included 268 samples, consisting of 167 patients and 101 healthy people. These studies were analyzed, and then a meta-analysis was performed.

Common genes that led to significant decrease or increase in gene expressions were identified and their biological, molecular, and cellular pathways were examined. In general, it was found that this set of genes can be involved in asthma and some pathways affecting the function of disease.

According to current findings, examining the objectives of efficacy and functional analysis of new genes effective in asthma and their protein products, and also investigating the role of interactions in asthma could help in taking appropriate treatment strategies to control asthma complications and injuries.