فصلنامه کومش
سال بیست و پنجم شماره 1 (پیاپی 93، بهمن و اسفند 1401)

Today, treatment with CAR-T cells is accepted as an effective treatment for blood malignancies. CAR-T cells are autologous T cells that are engineered by gene transfer techniques to express a chimeric antigen receptor (CAR). Despite the promising results and the approval of six CAR-T cell products; these products have not yet been approved for solid tumors. In addition, the high cost of treatment with CAR-T cells has limited patients' access to these life-saving drugs. Therefore, key considerations in the design and development of CAR-T cells should be defined and methods of reducing the cost of this treatment method should be investigated.

This study was performed based on an accurate bibliography through research databases such as PubMed, Scopus, Web of Science, and Google Scholar search engine, as well as the websites of pharmaceutical companies.

CAR synthetic receptors contain an antigen-recognizing extracellular region that connects to the space-forming, transmembrane and intracellular messenger regions. Each part of the CAR structure affects some functions of CAR, including target recognition, activation and cell lysis. So far, five generations of CAR-T cells have been developed to improve the messaging capacity of these cells. In addition, gene transfer systems such as electroporation, transposon and genome editing systems have been introduced as an alternative to viral vectors to produce safe and affordable CAR-T cells. Also, the development of ready-to-use products, product production in places far from the place of consumption, new pricing platforms and methods, and health insurance system initiatives have been suggested as ways to reduce prices.

In this article, an overview of how to develop CAR-T cells, important factors in the design of chimeric receptors, different methods of gene transfer and solutions to reduce the cost of this treatment were discussed. By using these strategies, the potential of CAR-T cells in cancer immunotherapy can be fully utilized.

Colorectal cancer is one of the most common cancers in the world. Various factors are involved in the development and progression of this disease. One of these agents is cyclooxygenase-2 (COX-2). COX-2 is a product of the PTGS2 gene and converts free arachidonic acid to prostaglandins. COX-2 is not naturally expressed in most normal cells. Noticeably, the increased expression of COX-2 has been observed in chronic inflammatory diseases and various cancers. COX-2 promotes colorectal cancer through various signaling pathways. COX-2 plays its role in colorectal cancer by induction of Bcl-2 expression, and β-catenin pathway activation, and leads to translocate of the NF-κB from the cytoplasm to the nucleus. NF-κB transcription factor plays an important role in physiological processes such as cell proliferation, cell death, and inflammation. Deregulation of NF-κB and its impact on the signaling pathway play a critical role in the development and progression of colorectal cancer. Another factor that plays a role in the development and progression of colorectal cancer is the β-catenin gene. Mutations in the β-catenin gene have been found in more than half of colorectal cancer patients. Bcl-2 is also known as an anti-apoptotic factor in all types of cancers. COX-2 controls all these pathways. Therefore, targeting COX-2 can be proposed as a therapeutic strategy for the treatment of colorectal cancer. The purpose of this review is to investigate the signaling pathways related to COX-2 in colorectal cancer

Osteoarthritis of the knee is the most prevalent type of arthritis that causes persistent pain and reduces the quality of life. However, no treatment alleviates symptoms or stops the disease from progressing. Functional magnetic resonance imaging (fMRI) studies can provide information on neural mechanisms of pain by assessing correlation patterns among the different regions of the brain. This study aimed to determine brain connectivity patterns in patients with knee osteoarthritis compared to healthy individuals using advanced statistical models.

The data of this study were downloaded from https://openneuro.org/. These data included fMRI imaging of 36 knee osteoarthritis patients with a range age between 45-70 years old and 12 healthy individuals with a range age between 48-78 years old. Graph-based models were used to examine the brain functional alterations in knee osteoarthritis patients.

The results showed a disease-related cluster of eight regions in the brain, including the right Rolandic operculum, right amygdala, left caudate nucleus, left putamen, right putamen, left pallidum, and right pallidum. According to correlation comparisons in the cluster, the connectivity of 18 pair regions revealed a significant difference between the two groups. In comparison to the other regions, the right Rolandic and right amygdala had more communication.

Interestingly, in patients with knee osteoarthritis, the effect of chronic pain can cause functional alterations in the brain.

Due to participation being the main goal of rehabilitation in people with spinal cord injury, the distribution of services via telerehabilitation will be useful for most of these people who are no access to rehabilitation centers due to environmental barriers. Therefore, the aim of this research was to investigate the effect of telerehabilitation focused on transfer training and wheelchair mobility on the participation level of people with spinal cord injuries.

In a single-blind randomized controlled clinical trial, people with spinal cord injuries were randomly assigned to intervention and control groups. The intervention group received group and online training in 4 sessions during 4 weeks, so two-hour sessions were held every week. The control group did not receive any intervention. The wheelchair outcome measure (WhOM) was completed by the participants before and after the intervention. The WhOM has two parts, the first part consists of a semi-structured interview and the participants specified their goals based on participation at home (question 1) and in the community or outside the home (question 2). Then the participants scored the importance of each goal and their level of satisfaction with this activity. In the second part, structured questions are asked about comfort, satisfaction with the sitting position and skin damage.

44 people with paraplegic spinal cord injury participated in the telerehabilitation with an average age of 34.09 and a standard deviation of 8.19 and a control group with an average age of 35.50 and a standard deviation of 8.70. The average of all scores in the participants of the intervention group had a significant difference (P<0.001). Also except for the score related to the level of comfort with sitting position in the wheelchair (P=0.1) and participation scores at home {(P=0.23) (P=0.11)}, the results of the comparison between the two groups were significant (P<0.001).

Based on the results, telerehabilitation was effective in the participation level of people with spinal cord injuries. Also, the results showed telerehabilitation had a significant impact on the patient's level of satisfaction with participation in their daily activities.

The purpose of this research was to compare the effect of sleep and consciousness on consolidation based on implicit motor memory enhancement among youth, middle-aged and elderly.

The sample statistic consisted of 120 (youth, middle-aged and elderly) healthy and right-handed volunteers (40 people from each age group). The groups were availability selected and randomly divided into six experimental groups of implicit motor memory of youth, middle-aged, and elderly with a distance of twelve hours in the morning (without night sleep) and evening (with night sleep). This research included the acquisition and retention phases. In this research, the alternative serial reaction time task with random and repetitive sequences was used.

In the acquisition phase, the results of ANOVA with repeated measure test showed that the practice led to enhance mean of performance in random and repetitive reaction time in 5-epoch. In the retention phase, the main effect of the practice epoch was significant (P<0.05) and all six groups were better than the 5-epoch in the acquisition phase. Also, the results of the Duncan posthoc test showed that the youth, middle-aged and elderly groups with 12h retention test delay, were better performance than the practice session.

Generally, night sleep with 12h retention test facilities the process of consolidation based on implicit motor memory enhancement among youth, middle-aged and elderly people.

Buxus hyrcana Pojark. has been traditionally used for the treatment of skin disorders including wound injuries and recent studies have shown the therapeutic potential of some Buxus species in healing skin wounds. In this study, the effect of an ointment containing methanolic extract of B. hyrcana leaves was evaluated on the full-thickness wound healing in a rat model.

The full-thickness wound was made with a scalpel on the dorsum cervical area of 32 Wistar rats (weighing 250-300 g). The animals were randomly divided into four groups: I; control, II; ointment base (eucerin), III; 1 % phenytoin cream, and IV; 5 % B. hyrcana methanolic extract ointment. For histopathological assessment, wound criteria were evaluated on the 12th day of treatment according to the Abramov score method. The collagen fiber deposition in the skin tissue was determined using Masson’s trichrome staining. The spectrophotometric analysis was performed to evaluate the total phenol and total flavonoid content of the extract.

Based on macroscopic observations, herbal ointment increased wound closure in the treatment group compared to the control group. In this way, the collagen deposition, epidermal and keratin formation, neovascularization, and fibroblast maturation increased significantly (P<0.05) with the herbal ointment, the same as the phenytoin group. The extract did not show any antimicrobial effect using the disc agar diffusion method.

The observed wound-healing effect of B. hyrcana seems to be mainly due to the presence of flavonoid compounds in the plant extract.

The occurrence of nausea and vomiting is one of the most common complications after surgery. Considering the preventative effect of Pofol on such PONV, the present study evaluated the effect of two different Propofol doses on the prevention of nausea and vomiting in discectomy surgery.

The present controlled triple-blind clinical trial was performed on 48 patients that were candidates for discectomy surgery under spinal anesthesia and were randomly allocated into three groups. Two different propofol doses of 0.1 and 0.2 mg/kg were intravenously administered in the Pofol 0.1 and 0.2 groups, respectively, with the third placebo group being used as a control group.  Hemodynamic parameters, the severity of nausea and vomiting, and the incidence of complications were evaluated.

The results of the present study revealed that the severity of nausea and vomiting in the control group was still more than that of the two propofol groups (P-value <0.05); however, a significant difference was found between the two Pofol doses in terms of the severity of nausea and vomiting (P = 0.02).

According to the results of the present study, a low dose of Pofol 0.1 is effective in reducing nausea and vomiting after surgery, but it is less effective than a 0.2 dose of propofol.

Nordic walking training has many benefits in improving the condition of the disabled elderly. Then the aim of this study was to evaluate the effect of Nordic walking training on plasma levels of PGC1α and SIRT6 in elderly women with diabetes.

In this quasi-experimental study, 27 elderly women (age: 65.45±2.70 years) with type 2 diabetes were selected and randomly divided into control groups (n=14) and experimental groups (n= 13). Then, the experimental group performed exercise protocol of Nordic walking training, three days per week for eight weeks. Blood samples were collected before and after the training protocol. ELISA kit was used to measure the biochemical variables of the research.

The analysis of data showed that the levels of PGC1α and SIRT6 in the exercise group compared to the control group increased significantly (P<0.001) and glucose, insulin and resistance of insulin decreased significantly (P<0.001).

Nordic walking training, could reduce glucose, insulin and resistance insulin and increases PGC1α and SIRT6 in elderly women with diabetes, and help improve the metabolic system of the elderly.

Breast cancer is the most common malignancy in the female population and is the leading cause of death. Surgery, chemotherapy, radiotherapy, and monoclonal antibody (trastuzumab) therapy are common and standard treatments for this cancer. However, there are significant limitations in the treatment of this disease by using regular methods. Given the role of transcription factors (TFs) in gene expression, differentiation therapy, and many cancer signaling pathways, in the present study, the effect of combined treatment of trastuzumab (Herceptin) and decoy oligodeoxynucleotides to target the STAT3 transcription factor on inhibition of HER2 positive SK-BR-3 cell line growth was investigated.

At first, different concentrations of Trastuzumab were prepared from 0.1 to 100 μg/mL. In this way, the decoy and scramble oligodeoxynucleotides were designed and synthesized to target the STAT3 transcription factor. The transfection efficiency and combined effects of trastuzumab with decoy oligos on cell viability, apoptosis, and cell migration inhibition were evaluated.

The results showed that oligodeoxynucleotides labeled with Cy3 fluorophore (300 nM) enter the cells with high efficiency (81.7±6.9%). Combined treatment of cells by trastuzumab (10 μg/mL) along with decoy oligodeoxynucleotides (100 nM) led to a decrease in cell viability (58.86±2.71%), increased apoptosis (24.54±4.83%) and inhibited cell migration (45.95±4.21%).

The results from this study showed the anticancer effects of combination therapy using trastuzumab with decoy oligodeoxynucleotides to target the STAT3 transcription factor in SK-BR-3 cells. Therefore, it seems that this strategy can be used as an adjunct to common treatments for breast cancer.

The tonsils are part of the immune system and tonsillar infection is one of the most common causes of diseases, especially in children. Tonsillitis sometimes does not respond to empirical treatment and the presentation of recurrent tonsillitis eventually leads to tonsillectomy. The aim of this study was to determine and compare palatal tonsil culture by superficial and deep methods in frequent tonsillitis patients referred for tonsillectomy.

This cross-sectional study was performed on all patients aged > 3 years with chronic recurrent tonsillitis referred for tonsillectomy during 2019-2020. After obtaining the informed consent of the patient's legal guardian, the patient underwent sampling of the right palatine tonsil with a swab through the mouth before tonsillectomy. After tonsillectomy, a sampling of the surface and deep tissue of the tonsil was performed. Microbiological examination, antibiogram determination, and blood culture before and after tonsillectomy were performed.

A total of 80 patients were recruited in this study of which 50% were male. In 87.1% of patients, the report of staphylococcus (as the most common organism found) had poor consistency in both surface and deep culture methods. This rate reached 81.3% in comparison between deep tissue culture results and secretions (swab) and 72.7% in comparison between surface samples and secretions (swab) (P<0.001). There was the lowest amount of negative cultures in the comparison of 3 surface cultures, deep cultures and secretions (swap) in deep samples. The highest antibiotic susceptibilities against tonsillar organisms were observed in clindamycin, erythromycin, cefoxitin, gentamicin, and doxycycline.

Blood cultures before and after tonsillectomy were negative in all samples. Based on the results, it seems that no persistent infection enters the blood during tonsillectomy in otherwise healthy patients. It also seems that the use of deep culture is more beneficial compared to surface culture because it has a lower false negative rate.

Acute coronary syndrome, the most common form of heart disease, is the main cause of disability and death. It impairs the hemodynamic indices, leading to endangering the patients' condition. Curcuma Longa modulates blood pressure, breathing parameters, and temperature. The present study aimed to investigate the possible protective effects of Curcuma Longa on hemodynamic indices in acute coronary syndrome patients.

In this triple-blind clinical trial, 270 patients with acute coronary syndrome from the Coronary Care Unit in Kowsar Hospital in Semnan were included in the study from December 2019 to March 2021. Then, they were randomly divided into three groups, including the sham, intervention, and control groups (n=90). The intervention group received 500 mg of Curcuma Longa tablets. The sham group received 500 mg starch, Oisel, and lactose tablets. Drugs were administrated at 9 am, soon after breakfast, for 3 days. The control group received only the routine interventions. Before and 30 min after the intervention, the hemodynamic indices were recorded on 3 consecutive days using hemodynamic monitoring equipment (Pouyandegan Rah Saadat).

The average heart rate was significantly decreased in the intervention group than in the sham group (P=0.001 for day 1), (P<0.001 for day 2), and (P<0.001 for day 3). The average heart rate was significantly decreased in the intervention group than in the control group on the 2nd and 3rd days (P<0.001). Systolic and diastolic blood pressure were significantly decreased in the intervention group than in the sham, and control groups (P<0.001). Arterial blood oxygen saturation was significantly increased in the intervention group than in the sham and control groups (P<0.001).

Curcuma Longa reduces pulse rate, as well as systolic and diastolic blood pressure, and enhances arterial blood oxygen saturation in a triple-blind clinical trial study. The protective effects of Curcuma Longa on hemodynamic indices may highlight the use of this simple and affordable intervention in Coronary Care Units.

Being hospitalized is a restriction that can have a negative effect on the development of the child's areas, including motor and emotional; Therefore, the present study aimed to determine the effect of targeted movement games on the development of fundamental movement skills and depression of hospitalized children.

The design of the current study was a clinical trial with a pre-test and post-test with a control group. The research population consisted of obese children aged 4-7 years admitted to the children's department of Afzalipur Hospital in Kerman province, with various diseases such as diabetes, anemia, rheumatism, and nervous tics, 20 of them were selected purposefully and after performing a pre-test They were divided into two intervention and control groups by simple random method. To collect data, Brunnix-Ozertsky's Motor Skills Test (1978) and Fisher and Long's Depression Scale (1983) were used. Based on the duration of hospitalization until discharge from the hospital, the intervention group based on the length of hospitalization until discharge from the hospital, 7 sessions, 2 hours each day in the hospital game room under the independent variable (targeted movement games), and at the end, a post-test was performed on both groups.

The results showed that targeted movement games were effective in the development of gross and fine motor skills of hospitalized children, and targeted movement games had a significant effect on the depression score except for the subscales (guilt, pleasure).

In general, according to the results of this research, it can be said that the implementation of targeted movement games is a non-drug, new, easy, accessible, and suitable method for improving the movement problems and depression of hospitalized children

One of the most important barriers to organ transplantation and the consequent mortality of people on the waiting list for transplants in most countries is family refusal. As a result, recognizing the effective factors in family consent will provide a bridge to increase the rate of supply of organs needed for transplantation. Due to the various factors affecting organ donation, including cultural, religious, scientific, social, moral, religious, and legal dimensions, there is a need for comprehensive and up-to-date studies in this field. Therefore, in this narrative review article, we gathered and summarized the major and influential causes of family refusal among the next of kin of brain death cases It is suggested that some ceremonies and social activities be considered to familiarize the community with brain death and the process of organ donation. Also, it is necessary to organize meetings with religious authorities to present the humanitarian aspects of organ donation.

Nowadays, under the influence of global events and conditions, universities have become institutions to strengthen scientific and educational exchanges, and this role is affected by the two phenomena of globalization and internationalization. Globalization has created a transnational nature for technical and scientific capacities in the world and has influenced the expansion of the international higher education market. The internationalization of higher education refers to the set of activities related to the development of inter-university scientific exchanges and cooperation. In other words, it is a process by which a university integrates the international dimension in its teaching, research, and service functions. The purpose of this study was to identify the factors affecting the internationalization of medical education from the viewpoints of lecturers at Semnan University of Medical Sciences.

This study was applied in terms of purpose and was conducted in a descriptive and cross-sectional method. The statistical population included all lecturers (faculty and non-faculty members) of Semnan University of Medical Sciences in the academic years 2019-2020. According to Cochran’s formula, 155 lecturers were selected as the research sample. Correspondingly, The research instrument was a questionnaire based on the 5-point Likert scale and covered 7 domains. The content validity of the instrument was determined using the viewpoints of the panel of experts. The reliability of the questionnaire was calculated by Cronbach’s alpha coefficient of 0.82.

Analysis showed that among the factors mentioned from the viewpoints of lecturers at Semnan University of Medical Sciences, equipment-technological factors (mean of 4.23 out of 5), then structural-academic factors (mean of 4.11), and content-educational factors (mean of 4.04) have the effective factors on the internationalization of medical education at Semnan University of Medical Sciences.

It can be acknowledged that to expand the internationalization of the university, the equipment-technological, structural-academic, and content-educational factors must be considered by managers and those who are involved in the evolution and innovation packages in medical education.

Spontaneous rupture of ectatic vessels is possible in different vascular beds and it can be life-threatening. Rapid diagnosis and initiation of appropriate treatment are essential.

Case report: 

A 63-year-old man presented with chest pain in a state where he was sleepy. Vital signs at the time of admission included a systemic blood pressure of 90/70 mm Hg, heart rate of 100 beats per minute, tachypnea, and arterial blood oxygen saturation of 92%. Muffled heart sounds, normal lung and abdominal examination, coldness of all four end organs, and weak and filiform pulses were recorded. Electrocardiogram showed ST segment elevation in leads I and avL. The patient underwent echocardiography, which reported moderate pericardial effusion and possible hematoma inside the pericardial fluid. Emergency CT angiography showed only pericardial effusion and intrapericardial hematoma. Pericardectomy was performed and the patient's systemic pressure increased to 150/ 90 mm Hg. The patient was transferred to the angiography unit due to the persistence of chest pain, where severe ectasia of the coronary arteries and 100% occlusion of the first diagonal were suggested. Importantly, the general condition was good and full consciousness. After eight hours, the patient suddenly suffered from severe melena, and after half an hour, a cardiorespiratory arrest occurs.

Rapid treatment is necessary in possible cases of rupture of ectatic vessels and may prevent death and irreversible complications. Ecstatic vessels may be present in different vascular beds and this question is raised whether it is necessary to check other systems after determining the presence of ectasia in one system.