Vol. 5 (2023)

Original Article


Trend of COVID-19 Hospital Cases Fatality Rate in Iran: A Multicenter Study of 5318 Hospitalized COVID-19 Patients from March 2020 to March 2021

Mehdi Azizmohammad Looha, Seyed Amir Ahmad Safavi-Naini, Nazanin Taraghikhah, Mohammad Tayefeh Norooz, Nasser Malekpour Alamdari, Zahra Azizan, Nadia Zameni, Mohamad Amin Pourhoseingholi

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,

Background and Aim: Case fatality ratio (CFR) is an indicator of disease severity that can help policymakers make decisions. This study aims to evaluate the trend of CFR of hospitalized COVID-19 patients since the outset of the pandemic in Iran and identify variables that affect CFR.

Methods: 5318 confirmed COVID-19 inpatients were enrolled in this multicentric observational study. Patients admitted from March 20, 2020, to March 18, 2021, in three general hospitals were collected. The medical team gathered patients’ demographics, past medical history, and outcomes by reviewing patients’ medical records. The time trend of CFR was investigated by joinpoint regression analysis to calculate weekly percent change (WPC) and confidence interval (CI).

Results: Significant upward trend was observed in CFR of hospitalized COVID-19 patients during study weeks (WPC= 1.2, 95% CI: 0.7, 1.7; P < 0.001). The increase was more evident in men than in women (WPC: 1.4 vs. 1.1). The rise of CFR was observed in patients with cancer (WPC: 4.5), dialysis (WPC: 2.1), diabetes (WPC: 1.0), and old age (WPC: 1.0).

Conclusion: There was a significant rise in the trend of in-hospital CFR from March 2020 to March 2021 in Iran. This rise was also evident with the same rate in patients with old-age and DM. However, the rate of this rise was higher in male and cancerous patients. Worldwide variation was reported by few studies investigating the trend of hospital CFR, and further studies are warranted.

Use of Napsin-A, TTF-1, ER, GCDFP-15, GATA-3 and GATA-3 Markers to Differentiate Breast Metastasis from Lung Adenocarcinoma

Elham Askari, Mihan Pourabdollah, mahsa ahadi, Hasan Daraei

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,

Background and Aim: Breast carcinomas with metastasis to lungs and primary lung adenocarcinomas have significant overlap. This study aimed to investigate the differential expression of a panel of IHC markers in primary lung adenocarcinomas and invasive ductal carcinomas (IDC) of the breast.

Methods: In this cross sectional study, total of 50 specimens including 25 primary lung adenocarcinomas and 25 invasive ductal carcinomas of the breast were collected from Masih Daneshvari and Shohada-e-Tajrish hospitals. After all of the cases were stained with hematoxylin - and - eosin, the histologic diagnosis and grading of the slides were reviewed and reported by experienced pathologists based on standard classifications. The patients’ medical records were reviewed for demographic data, clinical information and histopathologic reports.

Results: The median age of the patients with lung adenocarcinoma and IDC was 59 (32-78) and 50 (35-74) years, respectively. In this study, regarding lung adenocarcinomas, the most common type was acinar (56%), followed by solid (20%), mucinous (16%), lepidic (4%), and colloid (4%). Immunohistochemical expression for Napsin-A, TTF-1, ER, GCDFP-15, and GATA-3 in primary lung adenocarcinomas and invasive ductal carcinomas of the breast were different.

Conclusion: Napsin-A, TTF-1, ER, GCDFP-15, GATA-3 and GATA-3 Markers can differentiate the breast cancer from lung adenocarcinoma. Napsin-A and TTF1 only present in lung adenocarcinoma.

Increasing serum albumin in patients with hypoalbuminemia does not inhibit serum angiotensin-converting enzyme activity

Mitra Rezaei, Shiva Ghafghazi, Maryam Kazemzadeh Hemmesi, Mirmohamad Miri, Malek Zarei, Seyed Ali Ziai

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,

Introduction: Angiotensin-converting enzyme (ACE) plays a pivotal role in the production of angiotensin II and the inactivation of bradykinin. Recent studies have suggested that human serum albumin may possess ACE-inhibitory properties, serving as a potential endogenous ACE inhibitor that primarily affects serum ACE levels. Interestingly, the infusion of albumin in the postoperative phase of cardiac surgery has been associated with the development of hypotension.

Methods: This study aimed to assess serum ACE activity in 27 hypoalbuminemia patients admitted to the ICU before and after a protein-rich diet was administered to raise their serum albumin levels. Serum ACE activity was quantified using raas(HPLC), measuring the formation of hippuric acid, a product generated during the incubation of serum with Hip-His-Leu, a substrate, at 37°C for 30 minutes.

Results: In vitro experiments demonstrated that the addition of albumin to human sera led to a significant reduction in ACE activity compared to control groups (P < 0.0001). This reduction was consistent across all serum samples. Specifically, the maximum velocity (Vmax) of ACE activity significantly decreased from 14.90 U/L in the control group to 3.210 U/L in the albumin-added group (P = 0.0262). Notably, there was no significant change in the Michaelis constant (Km) between the control group (0.5263 mM) and the albumin group (0.2742 mM) (P = 0.6763), indicating a non-competitive inhibitory effect of albumin on ACE activity. Interestingly, in this study, elevating serum albumin levels in hypoalbuminemia patients following a protein-rich diet resulted in both ACE inhibition and a slight increase in activity (P = 0.0201). This increase correlated mildly with serum albumin levels across all samples.

Conclusions: In conclusion, contrary to in vitro findings, raising serum albumin levels in hypoalbuminemia patients did not further inhibit serum ACE activity.

Frankincense Derivatives Enhanced Bone Marrow and Spleen Cellularity Following Busulfan - Cyclophosphamide Conditioning Regimen

Sulaiman Al-Hashmi, Saeid Vakilian, Fatemeh Jamshidi-adegani, Juhaina Al-Kindi, Abdulaziz Al-Dhuhli, Mohammed Al-Broumi, Ahmed Al-Harrasi

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,
https://doi.org/10.22037/smsj.v5.42111

Background and Aim: The power of chemotherapy on prolonging and improving the life of patients is undeniable, but it often consists of various side effects. Therefore, developing of effective strategies for reduction of chemotherapy drugs toxicity is necessary. Natural products including frankincense - derived products have been demonstrated to reduce chemotherapy side effects. The aim of this study was to diminish the side effects of Busulfan - Cyclophosphamide (Bu - Cy) regimen as chemotherapeutic agents with the aid of frankincense derivatives administration in the mice model.

Methods: The chemotherapy conditioning regimen was created in Female Balb / c mice by intraperitoneal injection of 60 mg Busulfan and 150 mg Cyclophosphamide per kg of mice. Frankincense derivatives including essential oil (Ess), soxhlet oil (Sox) and n-hexane extract (Ext) were extracted and injected intraperitoneally to chemo - conditioned mice.

Results: As expected, mice treated with Bu - Cy chemotherapy had lower bone marrow cells count and spleen index compared to the control, whereas frankincense derivatives helped reducing side effects and modifying immune system and general health.

Conclusion: Despite that all three extracts have decreased the side effects of chemotherapy; Ext could simultaneously increase the spleen index and the bone marrow cells count and also improve the health in comparison with the negative control group.

Induction and evaluation of acute inflammatory model of sulfur mustard analogue (CEES) in C57BL/6 mice

Mahtab Tapak, Somaye Sadeghi, Tooba Ghazanfari, Nariman Mosaffa

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,
https://doi.org/10.22037/smsj.v5.42917

The acute threat model with mustard analogs has been produced and synthesized due to the dangers that sulfur mustard can pose to users in experimental work conditions and the creation of sulfur and numerous analogs to prevent its dangers. To evaluate the confirm of 2- Chloroethyl Ethyl Sulfide (CEES) as an analog of SM, we set up a new model of CEES systemic injection & exposure to be as close as possible role of this toxin analog effects on innate immune inflammation. Female C57BL/6 mice, 8-10- week old at the onset of the study, were exposed to CEES (10 mg / kg). The administration route was Intraperitoneal (IP) injection. At the end of the study, the mice’s lung fluid, and peritoneal lavage, spleen lymphocyte and lung tissue were extracted for future histopathological assessments.

Isolation of Mesenchymal Stem Cells (MSCs) from Wharton’s Jelly (WJ) Tissue of Human Umbilical Cord (hUC); a Protocol

Fatemeh Ahangari, Zahra Mirsanei, Sara Soudi, Sahar Ghaffari Khaligh, Sara Soufi, Seyed Mahmoud Hashemi

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,
https://doi.org/10.22037/smsj.v5.42169

Mesenchymal stem cells (MSCs) with their spindle like shapes are a lineage of stem cells with the capacity to self-renew and differentiate into osteoblasts, adipocytes, and chondrocytes and with CD105, CD73, and CD90 expression and the lack of CD34, CD14, CD45, and HLA - DR expression. The immunomodulatory, angiogenic, antiapoptotic, antimicrobial, and antioxidative characteristics of these cells made them more attractive in the field of cell - therapy for several autoimmune and inflammatory diseases, including diabetes, neurological disorders, sepsis, cardiac ischemia, and GvHD. For this reason, various protocols have been proposed to isolate mesenchymal stem cells from different tissue sources, such as adipose tissue (AT), umbilical cord (UC), Wharton’s jelly (WJ), bone marrow (BM), dental pulp, and even menstrual fluid. Considering the ease of access to the umbilical cord tissue and the fact that this tissue is rich in MSCs with embryonic origin and higher proliferation rate and lower senescence of the cells, the umbilical cord became a suitable source for explant MSC culture. In this study, we decided to introduce an explant culture protocol of MSCs that is less expensive and cost - effective achieving a high yield of MSCs.

Case Report


A rare Diagnosis Perforated Gastric Ulcer in a 10 years old Girl, A rare Diagnosis for Age: A case report

Ahmad Reza Shahraki

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,

Perforated gastric ulcer (PGU) is exceedingly uncommon in children. In a child with acute abdomen and Pneumoperitoneum, an Appendiceal etiology is more often suspected as a likely cause. Failure or delay to diagnose a PGU can result in significant morbidity and even mortality.

We report a 10 years old girl with abdominal pain for 2 days with PGU. We did examination and we found generalized abdominal pain and performed Laparatomy and we found perforated gastric ulcer and repair with Omental patch. PGU is an uncommon cause of peritonitis in children and poses significant challenges in management. Strong suspicion and prompt appropriate intervention is necessary to avoid untoward outcomes. Researchers conclude that GOO secondary to ulceration can occur in the absence of H. pylori infection. PPU is a rare cause of abdominal pain in children, but still a PUD complication that requires surgery. PPU should be included in the differential diagnosis in patients presenting with acute abdominal pain of uncertain etiology and pneumoperitoneum. Laparoscopy is both diagnostic and therapeutic. Laparoscopic omental patch repair is a safe and effective treatment for PPUs. This case illustrate that perforated peptic ulcers should be considered in children presenting with acute abdomen.

Congenital Colonic Stenosis: A Rare Gastrointestinal Malformation in Children

Fereshteh Karbasian, Zahra Vahedi, Kiarash Ziaee, Farhad Abolhassan Choubdar

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,

Congenital colonic stenosis is a condition in which there is a narrowing or blockage of the colon (large intestine) present at birth. This can occur due to multiple etiologies, including abnormal development of the colon during fetal development and some genetic defects. The condition may lead to symptoms such as abdominal pain, on and off constipation, abdominal distention and vomiting. Treatment may involve surgery to remove or widen the narrowed segment of the colon.

Short Communication


Important Tips to Improve the Impacts of a Research Paper: Pre and Post Publication Strategies

Amir Ahmad Safavi-Naini, AmirHossein Aghdaee

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,

We do research projects to expand human knowledge and solve real-world problems. Well said, Scott Fitzgerald, “an unread book is just a block of paper.” Researchers should increase the visibility of their paper; otherwise, the value of a research paper is limited to just a file and a Doi. Here we presented some tips for authors to improve the visibility and citation number of their research [1]. The tips are gathered by reviewing the literature [2–8] and asking expert opinions.

 

After publication

Most of the researchers think that getting the acceptance of their research manuscript in a good journal is their final endeauver. They Although the best time for improving future scientific metrics of a paper is before publication, there are ways to increase the visibility of research after publication.

A.1. Research communities and social media

You can share your article in social media conducted for scientific communities (i.e., LinkedIn, Research gate, Elsevier, Mendeley, Google Scholar, ORCID). Moreover, sharing your research on Twitter boosted the citation number by 43% [9]. You can gain the interest of your audience by sharing an exciting piece of your findings and providing the link to the article on your social media or webpage (Check with publisher first). Inserting audio or text content from your paper on the web may give a 50% increase the paper's citation [2].

Articles covered in the news get 13 times higher citation numbers [10]. Therefore, you can increase the visibility of the research paper by contacting a journalist to cover your work. -Cont.

Study Protocol


A novel protocol for the establishment of in vitro intrauterine adhesions model

MirMohammadReza Hosseini, Kimiya Rashidan, Hadis Gandomkar, Ahmadreza Faraji, Nariman Mosaffa, Hossein Ghanbarian, Sahar Ghaffarikhaligh, Seyed Mahmoud Hashemi

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,

Background and aim: Intrauterine adhesions (IUAs), also known as Asherman's syndrome, is a prevalent gynecological condition that presents with various clinical manifestations, including atypical menstrual patterns, pelvic discomfort, reduced endometrial thickness, repeated pregnancy loss, and potential infertility. Despite advancements in therapy, the successful pregnancy rate remains low, especially in severe cases, posing significant therapeutic challenges and poor prognoses. Therefore, extensive research is essential to understand the underlying mechanisms of IUAs and develop effective therapeutic interventions.

Materials and Methods: This study introduces a novel method of incubating co-culture of stem cells and intraperitoneal macrophages with hydrogen peroxide (H2O2) and scratch wound to mimic impaired endometrial stromal cells, considering the regenerative properties of macrophages, and prominent leukocytes in the endometrium. The objective was to examine the co-culture endometrial stem cells (EnSCs) of the human uterus and intraperitoneal macrophages as an in vitro model for IUAs. The aim was to establish a physiologically relevant model that replicates the complex cellular interactions and microenvironment observed in the endometrium during IUAs development and investigate the influence of macrophages on the response of stem cells to H2O2.

Results: The study involved culturing and preparing EnSCs in a 24-well plate, while peritoneal macrophages were isolated through lavage in mice. Four experimental groups were established: EnSCs alone (group A), EnSCs treated with H2O2 (group B), EnSCs co-cultured with macrophages (group C), and EnSCs co-cultured with macrophages treated with H2O2 (group D). In all groups, the wound was mimicked by a sterile crystal tip. Cell viability was assessed using the MTT test, measuring the reduction of tetrazolium salt to formazan crystals. Nitric oxide (NO) production was measured using the Griess reaction, and cell migration was evaluated through a scratch wound healing assay. Statistical analysis utilized Student's t-test or one-way ANOVA, with GraphPad Prism version 6 software, considering results with p< 0.05 as statistically significant.

Conclusion: The findings indicated that H2O2 treatment had a negative impact on EnSCs viability, but co-culturing with macrophages provided a protective effect. Moreover, H2O2 treatment led to increased NO levels, suggesting macrophage activation against oxidative stress. Interestingly, H2O2 treatment promoted cell migration in both EnSCs alone and the co-culture, while macrophages inhibited migration. These results underscore the significance of the interaction between EnSCs and macrophages in understanding IUAs and developing effective treatments

Keywords: Intrauterine adhesion; Macrophages; Endometrial Stem cell; in vitro; Scratch wound

Visual Practice


A 20 days visual follow up on Herpes zoster (shingles): Diagnosis, treatment and clinical outcome

AmirHossein Aghdaee, Seyed Mahmoud Hashemi

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,

A 44-year-old man with a three-day history of pain in right axilla, subsequently accompanied by the appearance of vesiculopapular rashes on the right portion of his torso, attended a medical facility. The patient had neither reported any special skin contact in that area, nor fever and other symptoms. Upon examination, the examiner revealed the appearance of some other similar vesiculopapular rashes. These two affected sites were located in a linear arrangement, namely, the T7 dermatome. Considering the particular arrangement of rashes and form of manifestation, a clinical diagnosis of herpes zoster was made. The patient underwent empirical treatment of herpes zoster, including Virabex (valaciclovir) tablet 1g TDS, pregabalin capsule once nightly, and hydroxyzine hydrochloride tablet once every night. The pain and itching resolved within one week after the prescription, and the rashes mostly disappeared within 20 days. Here, the daily state of rashes are presented to the audience.

Phagocytosis of yeasts by lipopolysaccharide (LPS)-stimulated macrophages

Mohammad Mahmoudi, Mahsa Taghavi-Farahabadi, Seyed Mahmoud Hashemi, Kazem Mousavizadeh, Nima Rezaei, Nazanin Mojtabavi

School of Medicine Students' Journal, Vol. 5 (2023), 30 December 2023,
https://doi.org/10.22037/smsj.v5.40522

For phagocytosis measurement, 5×105 macrophages were seeded in a 12-well plate. 20 ng/ml LPS was added to cells to induce the M1 phenotype. After 24h the medium was changed. A suspension of heat-killed baker’s yeast was prepared at 108 particles per ml in DMEM medium. The yeast suspension was added to macrophages at a ratio of 1:10 (macrophage: yeast). Macrophages were allowed for 60 minutes to phagocyte the particles at 37°C. To remove the free yeasts, the well was washed with PBS. The phagocytosis was observed using an inverted microscope.