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Objective To investigate the regulatory mechanism of apurnic/apyrimidinic endonuclease 1(APE1) in the transformation of chronic intestinal inflammation to colitis-associated colorectal cancer (CAC). Methods C64S mutant (APE1C64S) mice and APE1 wild type (APE1WT) mice were randomly divided into experimental group and control group.In vivo CAC model was established by azoxymethane (AOM) and dextran sulfate sodium salt (DSS) solution.Immunohistochemistry (IHC) and multiple IHC (mIHC) assays were used to observe the expression of APE1 and immune cell infiltration in colon tissues of each group.A mouse colon cancer cell line MC38 with stable knockdown of APE1 was constructed by lentivirus transfection, and subcutaneous tumor bearing experiments were performed in APE1WT and APE1C64S mice to confirm that tumor cell-derived APE1 caused immunosuppressive tumor microenvironment.The expression of APE1 and CXCL1[chemokine (C-X-C motif) ligand 1]and the infiltration of immune cells in tumor-bearing specimens were analyzed by IHC and mIHC assays.The tumor specimens of a 28-year-old female patient with CAC from Army Medical Center of PLA were analyzed for the expression of APE1 and CXCL1 and the infiltration of immune cells in the tumor and adjacent inflammatory tissues by IHC and mIHC assays. Results Compared with the control group and APE1WT erperimental group, APE1C64S erperimental group had significantly reduced disease activity index and tumor formation, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) infiltration, and CD4+ and CD8+T cells (P < 0.05).No significant differences were observed in tumor growth and immune cells between APE1WT and APE1C64S mice bearing subcutaneous tumors.However, in the tumor-bearing experiment using tumor cells with knockdown of APE1, the tumor growth was significantly lower and the number of infiltrated PMN-MDSCs was reduced, while those of CD4+ and CD8+T cells were significantly increased (P < 0.05).Furthermore, high expression of APE1 and increased infiltration of PMN-MDSCs were found in the tumor tissues of the young CAC patient, and CD8+T cells were significantly reduced in the tumor tissues compared with the inflammatory tissues (P < 0.05). Conclusion APE1-redox in tumor cells can promote the infiltration of PMN-MDSCs and reduce the number of T cells, thereby forming an immunosuppressive tumor microenvironment and mediating the occurrence and development of CAC.

Objective To explore the expression of prohibitin (PHB) in tumor tissues and analyze its effect on the prognosis of patients with digestive system malignant tumor (DT) and its mechanism. Methods ① The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database were used to compare the expression of PHB in tumor tissues and normal tissues.②Five pairs of gastric cancer and adjacent tissues and 5 pairs of colon cancer and adjacent tissues were collected, and RT-qPCR was used to verify the mRNA expression levels.③RT-qPCR and Western blotting were used to verify the differential expression of PHB in normal gastric mucosa cells (GES-1), gastric cancer cells (AGS, MKN45 and HGC27), normal colon cells NCM-460 and human colon cancer cell line SW480.④R language was used to analyze the effect of PHB on the prognosis, tumor microenvironment, tumor mutation burden and microsatellite instability of DT patients.⑤CIBERSORT algorithm was used to study the correlation between PHB expression in tumor tissues and tumor immune cell infiltration.Gene Set Enrichment Analysis (GSEA) was used to explore the biological function of PHB.⑥R language was used to analyze the relationship between PHB and drug sensitivity. Results ① PHB was highly expressed in colon cancer, cholangiocarcinoma, esophageal cancer, liver cancer, rectal cancer and gastric cancer (P < 0.01).②RT-qPCR and Western blotting showed that PHB was highly expressed in the tissues and cell lines of gastric cancer (P < 0.01) and colon cancer (P < 0.01).③The differential expression of PHB was associated with poor prognosis of hepatocellular carcinoma (P=0.002).In cholangiocarcinoma, gastric cancer, pancreatic cancer, liver cancer and esophageal cancer, PHB was positively correlated with tumor mutation burden and microsatellite instability (P < 0.05).④PHB was positively correlated with M2 macrophages in colon cancer (P=0.03).In cholangiocarcinoma, it was positively correlated with activated CD4+ memory T cells (P < 0.05).In esophageal carcinoma, it was positively correlated with activated hypertrophy (P=0.03).It was positively correlated with M0 and M2 macrophages and monocytes in hepatocellular carcinoma (P < 0.05).It was positively correlated with resting dendritic cells, eosinophils and activated CD4+ memory T cells in rectal cancer (P < 0.05).It was positively correlated with M0 macrophages, activated mast cells, neutrophils, resting natural killer cells, activated CD4+ memory T cells and follicular helper T cells in gastric cancer (P < 0.05).⑤PHB was mainly enriched in class I receptors, PPAR and calcium signaling pathways (P < 0.05).⑥ The expression of PHB was positively correlated with the sensitivity of 13 drugs, including ammonafide, prasinolide and abiraterone (P < 0.05). Conclusion The expression of PHB is significantly related to the infiltration of various immune cells in DT and poor prognosis in DT patients, which may become a new biomarker and potential immunomodulatory target of DT.

Objective To establish an animal model and evaluation system for lymph node metastasis of breast cancer. Methods A total of 60 female BALB/c mice (6~8 weeks old) were subjected, and then 6 models of lymph node metastasis (n=10) were constructed through injection at different parts in the mice with cell suspension of 4T1 breast cancer cells.Transgenic mice (n=5) of mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) were employed and served as model of spontaneous tumor metastasis.Then the advantages and disadvantages of different lymph node metastasis models were comprehensively evaluated from multiple aspects, such as operability, histomorphology and pathological detection, tumor growth rate and mouse survival. Results Among the 7 metastasis models, 4 models of lymph node metastasis were successfully established.Among them, the PyMT mouse spontaneous tumorigenesis model showed the best clinical reproduction, with a tumorigenesis rate of up to 100%, but had a disadvantage of poor experimental standardization.The hind paw-popliteal lymph node model had the fastest lymph node metastasis, easy operation and high repeatability, and a tumorigenesis rate of 100%, indicating its suitable for lymph node metastasis related research.The thigh subcutaneous-inguinal lymph node model also successfully simulated lymph node metastasis, with simple operation and high repeatability, a tumorigenesis rate of up to 100%, but its metastasis time was slightly longer than the hind paw-popliteal lymph node model.The inguinal lymph node-contralateral lymph node model was also a successful lymph node metastasis model, but with difficult operation, only 50% tumor-bearing rate, and poor repeatability.Lymph node metastasis model was not successfully established in the other 3 tumor-bearing models (under the tongue-internal jugular scapular tongue muscle lymph node model, bone marrow-inguinal lymph node model and right upper back skin-axillary lymph node model) in a short time, with no tumor cells observed in the pathological sections. Conclusion Through the comprehensive comparison of multiple models, mouse hind paw-popliteal lymph node model is the most suitable for conducting related research.

Objective To explore the effect and mechanism of miR-208b-3p on energy metabolism in mice with heart failure (HF) induced by transverse aortic constriction (TAC). Methods Twenty-four mice were randomly divided into sham operation group (Sham group, n=6) and surgery group (n=18).TAC was used to establish an HF model in the surgical group, the sham group received the same surgical procedures as TAC, but no ligation of the transverse aortic arc.At the second week after TAC, the surgery group was randomly divided into Antagomir group (n=6), Antagomir-NC group (n=6) and TAC group (n=6).The mice of the Antagomir group and the Antagomir-NC group were injected with miR-208b-3p antagomir reagent (800 μg) and miR-208b-3p antagomir negative control reagent (800 μg), respectively by tail vein, twice a week, for 4 consecutive weeks.Echocardiography was performed at the 6th week after surgery to evaluate the cardiac function.HE staining and Sirius red staining were used to observe myocardial histopathology in mice.ATP assay was employed to detect the ATP level in myocardial tissues.RT-qPCR was applied to detect the expression of miR-208b-3p, mitochondrial genes (ND1, ND2, ND3, ND4, ND4L, ND5, ND6, CO1, CO2, CO3, CYTB, ATP6 and ATP8), POLRMT and 12S rRNA in myocardial tissues.Double luciferase reporter assay was conducted to detect the interaction between miR-208b-3p and the potential target gene POLRMT.Western blotting was utilized to detect the changes in the protein levels of POLRMT and ND1, CO2, CYTB and ATP8 in myocardial tissues. Results The expression of miR-208b-3p was significantly higher in myocardial tissues of the TAC group than the Sham group (P < 0.05).Echocardiography revealed that the ejection fraction, systolic and diastolic functions were significantly improved in the Antagomir group than the TAC group (P < 0.05).Pathological observation showed significantly improved cardiomyocyte hypertrophy, arrangement disorder and myocardial interstititial cell infiltration in the Antagomir group (P < 0.05).Compared with the TAC group, the ATP level was significantly increased (P < 0.05), the expression levels of POLRMT and mitochondrial gene transcripts (12SrRNA and 13 mitochondrial gene-coding polypeptides) were significantly increased (P < 0.05), but there were no changes in SDHA and SDHB levels in the Antagomir group.Double luciferase reporter assay indicated that miR-208b-3p bound to the CDS region of POLRMT.The protein levels of POLRMT, ND1, CO2, CYTB and ATP8 were significantly increased in the myocardial tissues in the Antagomir group than the TAC group (P < 0.05). Conclusion MiR-208b-3p inhibits the expression of mitochondrial genes by targeting POLRMT, aggravates mitochondrial energy metabolism disorder, and deteriorates cardiac insufficiency and ventricular remodeling in HF mice.

Objective To observe the effect of Lactobacillus casei(L.casei) on the depression-like behaviors of offspring rats induced by maternal separation (MS), and explore the potential action mechanism of probiotics to improve central nervous inflammation in depression-like behaviors. Methods MS stress was used to establish a depressed animal model in offspring.Female SD rats were randomly divided into control group (CON), MS group, and MS+L.casei group, with 8 animals in each group.The female rats and their offspring in the control group did not undergo MS intervention after delivery, while those in the MS group were separated 3 h each day, for 14 consecutive days after normal delivery.The offspring of the MS+L.casei group was given intervention of 8×108 CFU/(kg·d)L.casei gavage for 4 weeks.Source preference test (SPT) and forced swimming test (FST) were used to evaluate the changes in depressive behaviors of the offspring rats.ELISA was employed to determine the levels of TNF-α, IL-6, IL-1 β and IL-10 in serum and hippocampus tissue.Real-time fluorescence quantitative PCR was applied to detect the mRNA expression levels of indoleamine 2, 3-dioxygenase-1(IDO1) and 5-HT mRNA in hippocampus. Results Compared with the CON group, the offspring in the MS group had significantly reduced percentage of source preference (P < 0.05), prolonged immobility time during forced swimming (P < 0.05), and decreased number of grid crossings in spontaneous activity test (though no statistical difference), indicating that the offspring rats had obvious depression-like behaviors after MS.L.casei treatment improved the behavioral changes of offspring rats caused by MS stress, with significantly increased percentage of source preference (P < 0.05) and shortened immobility time of forced swimming (P < 0.05).Compared with the conditions in the MS group, L.casei reduced the levels of IL-6, IL-1 β and TNF-α(P < 0.01) and increased that of IL-10(P < 0.05) in the hippocampus and peripheral blood, and decreased mRNA level of IDO1 and enhanced 5-HT mRNA level in hippocampus (P < 0.01) in the offspring rats of the MS+L.casei group. Conclusion MS stress induces depression-like behavior in offspring rats.L.casei inhibits the hippocampal expression of IDO1 and enhances that of 5-HT by regulating inflammatory factors in hippocampus and peripheral blood, and thus, improves depression-like behavior.

Objective To establish an artificial intelligence (AI) diagnostic model for the histopathologic diagnosis of extramammary Paget's disease (EMPD) and to evaluate its efficiency for the diagnosis and differential diagnosis of EMPD. Methods All non-tumor skin disease patients who underwent skin tissue biopsy in Department of Dermatology of First Affiliated Hospital of Army Medical University from September 2003 to February 2023 were recruited, and their pathological data were collected, including EMPD, Bowen's disease (BD), squamous cell carcinoma (SCC), and epidermal hyperplasia and hypertrophy. With EMPD as the main research subject, the histopathological images of BD, SCC, and non-tumor skin diseases were included in the study. The histopathological data of 4 types of diseases was classified and diagnosed by ResNet101 and DenseNet121 deep learning neural networks, and the performance of these models was evaluated. Results The AUC values of the ResNet101 diagnostic model for the diagnosis of EMPD, BD, SCC and non-tumor skin diseases on the images at ×20 magnification were 0.97, 0.98, 1.00 and 0.96, respectively, with an accuracy of 0.925±0.011, while the AUC values on the images at ×40 magnification were 1.00, 0.99, 1.00 and 0.97, respectively, with an accuracy of 0.943±0.017. The AUC values of the DenseNet121 diagnostic model for the diagnosis of 4 diseases on the images at ×20 magnification were 0.98, 0.95, 0.99 and 1.00, respectively, with an accuracy of 0.912±0.034, while the AUC values on the images at ×40 magnification were 0.99, 0.96, 1.00 and 1.00, respectively, with an accuracy of 0.971±0.012. Our results indicated that the histopathologic diagnostic model could effectively differentiate EMPD from BD, SCC and non-tumor skin diseases at low power magnification. The FLPOs of ResNet101 was 786.6 M, and the parameter was 4.5 M; The FLPOs of DensNet121 was 289.7 M, and the parameter was 0.8M. Conclusion Our AI diagnostic model is of good effectiveness in the diagnosis and differential diagnosis of EMPD. DenseNet121 is recommended as the dermatopathological diagnostic model of this study.

Objective To explore the feasibility of electrical impedance tomography (EIT) for real-time and accurate monitoring of respiration during HP anti-G movements and the key parameters of pulmonary ventilation. Methods Twelve healthy male students in our university were enrolled in September 2023 and subjected in this study. HP anti-G movements were performed 3 times each for 30 s in the anti-G physiological training apparatus, during which EIT and ophthalmic horizontal arterial pressure were measured to analyze the relationship of the global and local parameters of pulmonary ventilation, including inspiratory volume (IV), expiratory uniform (EU), expiratory speed (ES), center of ventilation (COV) and right-to-left lung ventilation ratio (RtoL) with anti-G ability of anti-G straining maneuver (AGSM). Results The average eye horizontal systolic blood pressure (SBP) at the eye level was 148.82±22.75 mmHg during HP anti-G movements, which was significantly higher than that during quiet breathing (PJ) (95.17±8.51 mmHg, P < 0.001). From the global pulmonary ventilation, the participants had significantly increased IV during HP anti-G movements (P < 0.001). According the d value (mean increase of eye horizontal SBP=SBPHP - SBPPJ), the subjects were divided into 3 groups, with the d value of >60, 30~60 and < 30 mmHg, respectively. The inspiratory volume ratio (IVHP/IVPJ) was the highest in the >60 mmHg group and the smallest in the < 30 mmHg group (P < 0.01). The subjects had significantly decreased EU and more evenly expiration (P < 0.05), but no change was seen in the expiratory uniformity ratio (EUHP/EUPJ) among the 3 groups. ES was obviously faster during HP anti-G movements (P < 0.001), and the expiratory speed ratio (ESHP/ESPJ) had no significant difference among the 3 groups. The inspiratory time and expiratory time were 0.77±0.32 and 1.59±0.21 s, respectively, and both of them were notably shorter during HP anti-G movements (P < 0.001, P < 0.01). From the local pulmonary ventilation, COV during HP anti-G movements was significantly smaller than that during PJ (P < 0.001), and the ventilation center deviated to the ventral side, and RtoL was decreased and the ventilation distribution deviated to the left lung (P < 0.05). Conclusion EIT can perform real-time imaging of pulmonary global and local ventilation during HP anti-G movements, and it has a great application prospect in AGSM training and monitoring.

Objective To determine the effect of enamel matrix derivative (EMD) on remineralization of artificial root dentin caries. Methods Bovine root dentin blocks were placed in a demineralization solution to create artificial root dentin carious lesions. The lesions were then randomly divided into EMD group (30 g/L EMD, the experimental group), sodium fluoride (NaF) aqueous solution group (1 g/L NaF, the positive control group) and distilled and deionised water (DDW) group (the negative control group), and all the lesions were pH-cycled at 6 cycles per day for 8 d. Morphology of the lesions were observed by scanning electron microscopy (SEM) and polarized light microscopy (PLM). Transverse microradiography (TMR) was used to examine mineral loss, lesion depth and mineral content. Results After pH-cycling, the surface morphology by SEM and the vertical morphology by PLM suggested that EMD and NaF treatment, but not DDW, caused mineral accumulation of artificial root dentin caries. Meanwhile, TMR revealed significantly lower mineral loss, shallower lesion depth and more mineral content in the EMD group than the DDW group (P < 0.05) after pH-cycling. Conclusion EMD can significantly promote remineralization of root dentin caries in vitro, and is a promising agent for non-invasive root caries therapy. [Key words] enamel matrix derivative , root caries , root dentin ,remineralization ,

Objective To investigate the application of exoscope in resection of parasagittal meningioma. Methods A retrospective analysis was conducted on 50 patients with parasagittal meningioma undergoing surgical treatment in a same medical group of our neurosurgical department from March 2021 to March 2023. According to their surgical procedures, they were divided into exoscope group (n=22) and microscope group (n=28). The surgical efficacy, surgical complications and surgical experience were compared between the 2 groups and analyzed. Results There were no significant differences between the 2 groups in terms of sex ratio (male/female: 10/12 vs 12/16), mean age (50.7±10.2 vs 52.3±11.1 years) and mean tumor size (20.79±25.04 vs 20.60±21.38 cm3). No statistical differences were observed in the duration of operation (217.73±59.66 vs 220.54±56.82 min), intraoperative blood loss (181.82±105.27 vs 189.29±103.06 mL), or total resection rate (90.9% vs 89.3%) between the 2 groups. Postoperative neurological dysfunction, infection rate and other complications also presented no notable differences between them. In the operation of parasagittal meningioma, exoscope can provide a larger view of the parasagittal sinus, such as the subdural border, which is difficult to be exposed by single microscope. Moreover, exoscope presented a higher level of comfort operating and better intraoperative teaching display compared to the surgical microscope. Conclusion For parasagittal meningiomas, exoscope is a safe and effective option, with similar surgical outcomes and postoperative complications as surgical microscope. What's more, exoscope presents more comfortable intraoperative ergonomic posture, higher surgical team participation, and better teaching effect.

Objective To investigate the effects of group identification on death anxiety among military medical students and the chain mediating effects of self-esteem and collective self-esteem. Methods Cluster sampling was conducted to survey the students in a military medical university in July, 2021, and finally survey data from 360 participants were collected through WeChat Mini Program, Questionnaire Star. The Questionnaires included Templer Death Anxiety Scale (T-DAS), Organizational Identification Questionnaire, Rosenberg Self-Esteem Scale-Revised (RSES-R), Collective Self-Esteem Scale and a self-designed general information questionnaire. Results ① The score of death anxiety in the participants ranged from 1.00 to 4.33 (M=2.60). ②The scores of group identification, self-esteem and collective self-esteem were negatively correlated with death anxiety (r=-0.56~-0.21, P < 0.01). Significantly positive correlations were observed in any 2 scores among the above 3 scores (r=0.42~0.68, P < 0.01). ③ Group identification significantly negatively predicted death anxiety (b=-0.21, SE=0.02, P < 0.001). ④ There were 3 mediation effects between group identification and death anxiety: group identification→self-esteem→death anxiety, group identification→collective self-esteem→death anxiety, group identification→self-esteem→collective self-esteem→death anxiety, with a total indirect effect of -017. Conclusion Group identification can negatively predict death anxiety among military medical students, and self-esteem and collective self-esteem play a chain mediating role between them.

Objective To explore the clinical significance of serum cytokine expression in the hepatitis B surface antigen (HBsAg) sero-clearance in patients with severe hepatitis B. Methods A nested case-control trial was conducted on 14 inpatients with severe hepatitis B admitted in our hospital from 2006 to 2020. Of them, 7 patients (aged 36.57±3.15 years) achieved HBsAg sero-clearance within 1 year after the onset of hepatitis B flares (with abrupt rise of ALT level to >5 times the upper limit of normal during HBV infection) and were assigned into HBsAg clearance group, while the other 7 patients (aged 34.14±2.97 years) only obtained HBsAg decreased less than 1 g within 1 year after the onset (HBsAg non-clearance group). Then, multiplex liquid-chip assay based on Luminex xMAP was used to detect the expression levels of 48 cytokines such as IFN-γ and IL-2 in serum samples of these 14 patients. Results The serum levels IFN-γ, IL-2Ra and SDF-1α were significantly lower in the HBsAg clearance group than the HBsAg non-clearance group (P < 0.05), but no statistical differences were observed in other 39 cytokines between the 2 groups. And there were 5 cytokines having no mutual expression in both groups. The copy number of HBV DNA was positively correlated with serum HGF (r=0.675, P=0.008) and SDF-1α levels (r=0.587, P=0.027), while negatively with IP-10 (r=-0.600, P=0.023) and MIG level (r=-0.640, P=0.014). Meanwhile, a positive correlation was found between HBsAg titer and IL12-p70 level (r=0.593, P=0.025), and a negative correlation between HBsAg titer and TNF-α level (r=-0.609, P=0.021). In addition, the serum total bilirubin level was positively correlated with the expression of SCGF-β (r=0.543, P=0.045). Conclusion Three differentially expressed cytokines and some cytokines related to HBV DNA level and HBsAg titer are found, which may provide new insights into the underlying immunological mechanism of HBV virus clearance caused by hepatitis flares. Meanwhile, it also provides potential biomarkers for HBsAg serological clearance in patients with severe hepatitis B.

Objective To investigate the changes and features of firing activities of interneurons in dorsal hippocampus during the acquisition and consolidation of associative memory. Methods Trace eyeblink conditioning (tEBC) was utilized as a behavioral model of associative memory.A total of 18 wild-type C57BL/6 mice (male, 10~12 weeks old, weighing 22~25 g) were randomly divided into a paired group (n=9) and an unpaired group (n=9).Paired presentations of conditioned stimulus (CS) and unconditioned stimulus (US) were utilized to train these mice.The mice from the paired group were given US training in 250 ms after CS training, and those from the unpaired group received similar doses of CS and US training, but with no paired relationship in time.After 4 consecutive days'training, the mice of the paired group acquired tEBC, manifesting conditioned eyeblink responses (CR).Tetrode arrays were applied to record neuronal activity in dorsal hippocampus during both tEBC training epoch and the 1.5 h epoch after training.The putative interneurons (n=105) were identified according to their firing rate and spike width from trough to peak.Specific changes in hippocampal interneurons activity during tEBC training and post-training slow wave sleep were analyzed respectively. Results ① At the early stage of CR acquisition (the 1st and 2nd days), CS could evoke significantly greater activity of dorsal hippocampal interneurons in the paired group (P < 0.05).During sharp wave ripples (SWR) in the post-training slow wave sleep, the firing rate of dorsal hippocampal interneurons was significantly lower in the paired group than the unpaired group (P < 0.05).②At the late stage of CR acquisition (the 3rd and 4th days), no significant differences in CS evoked activity of dorsal hippocampal interneurons were observed between the paired group and unpaired group, neither in the firing rate of dorsal hippocampal interneurons during SWR in the post-training slow wave sleep between the 2 groups. Conclusion The dorsal hippocampal interneurons show opposite changes in firing activity during the acquisition and consolidation of associative memory.

Mucormycosis is an opportunistic and progressive mycotic infection with a high risk of mortality. A filamentous fungus of the order mucorales is the pathogen responsible for this infection. We present a review of the literature. The aim of the study was to highlight and compare the cases of mucor mycosis affecting the districts of otolaryngological relevance, evaluating the outcome of patients undergoing surgical and / or medical treatment in the light of the presence of comorbidities. The bibliographic search was conducted on Pubmed by searching for the following keywords: “ENT mucormycosis”, “nose and paranasal sinuses mucormycosis”, “Rhino-oculo cerebral mucormycosis”. Mucormycosis is an infectious disease that requires early diagnosis and rapid therapeutic intervention, including the immediate involvement of a multidisciplinary medical, surgical, radiological and laboratory team. The combination of surgical and pharmacological strategies is essential for successful disease management.

Health-care workers are on the front line of the COVID-19 pandemic. In this occupational group, infection is of great concern due to the risk of nosocomial spread of the disease and significant reduction in the number of employees, it also endanger patient safety and compromise the capacities of health care workers. This is a cross-sectional study conducted among healthcare workers of university hospital of Farhat Hached Sousse who were affected by COVID 19 during September 1, 2020 to February 28, 2021. Data collection was carried out using an anonymous questionnaire about socio-professional and medical characteristics. Severity level of the SARS-CoV-2 infection was assessed according to the criteria of the National Authority for Health Assessment and Accreditation guideline (INEAS). Of the 555 healthcare workers with COVID-19, 477 participated. The factors associated with residual symptoms of COVID- 19 were: age (p=0.002), female gender (p=0.001), marital status (p=0.015), cardiovascular (p=0.001), endocrine (p=0.002) comorbidities, obesity (p=0.004), work position (p=10-3), professional work seniority (p=0.022), duration of confinement (p=10-3) and hospitalization (p=0.037).The use of antibiotics(p=10-3), anticoagulants (p=0.010) and corticosteroids (p=0.004) were significantly associated with the persistence of symptoms. After binary logistic regression, the factors associated with persistent symptoms were female gender, para-medical category, antibiotic and corticosteroid use. Long-term follow-up of HCWs with COVID-19 is recommended to understand and treat persistent symptoms after recovery. Protective equipment should be provided as well as vaccination for prevention and management.

The Kabuki syndrome (KS) represents a rare congenital condition characterized by a distinctive amalgamation of craniofacial anomalies, developmental irregularities, and intellectual impairments. This investigative pursuit aims to conduct an exhaustive exploration of KS via a detailed case series analysis, with a specific focus on elucidating its clinical manifestations and probing its genetic foundations. A cohort comprising nine KS patients was meticulously identified through a retrospective review of medical records spanning from 1996 to 2022. These patients underwent a comprehensive array of clinical assessments, radiological examinations, neuropsychological evaluations, and targeted genetic analyses, particularly centered on the KMT2D and KDM6A genes. The median age of diagnosis, approximately 4.7 years, demonstrated a male-to-female ratio of 6:3. Prominently evident among the clinical features were distinctive facial dysmorphisms, including arched eyebrows and elongated eyelashes, alongside ear anomalies, fingertip pads, nasolabial irregularities, and oral malformations. Ophthalmological and otological manifestations were notably discernible, along with a spectrum of cardiovascular, gastrointestinal, and endocrine abnormalities. The prevalence of neuropsychological disorders underscored the complex nature of cognitive and behavioral challenges experienced by KS patients. Consistent with our clinical observations, genetic analyses affirmed the involvement of variants in the KMT2D and KDM6A genes in the pathogenesis of KS. In conclusion, this investigation unequivocally underscores the paramount significance of accurate diagnosis, the adoption of a multidisciplinary care paradigm, and the implementation of tailored interventions for individuals afflicted by KS. Additionally, it highlights the imperative for sustained research endeavors aimed at unraveling the genetic intricacies and molecular mechanisms underpinning this enigmatic syndrome.

COVID-19 pandemic has had a profound impact on Italy. In this article, we conducted an analysis of mortality and lethality data from three provinces to extract valuable lessons learned from the management of the pandemic in Calabria. Data was collected from the Civil Protection of Calabria and analyzed for the period from March 2020 to January 2022. Statistical analysis, including spline-linear regression models and pairwise comparisons, was conducted to evaluate mortality and lethality rates among the provinces of Catanzaro, Reggio Calabria and Cosenza. In the province of Cosenza, higher overall mortality was observed; Catanzaro had higher lethality. Environmental and organizational factors may have influenced the severity of the virus in different regions. Future research should focus on sector-specific preparedness and individual well-being to enhance overall response to future pandemics.

What can be the triggers for a suicidal action? Is there a way to “notice” it in time? Is the person who ultimately threatens is more likely to carry it out? In the proposed case report, the authors examine the issue by illustrating the case of a woman who was depressed due to her divorce with her husband. She repeatedly staged a suicide attempt by hanging herself in front of her sons, later denying what she had done. Her suicidal intentions were realised after she saw herself in a video filmed by her daughter, in which she simulated hanging herself. The study addresses the complexity of suicidal behaviour, examining existing theories and challenges in diagnosis and classification. The factors involved in the woman's self-suppressive act are analysed, leading to the hypothesis that the “seeing herself again” forced her defence mechanisms, increasing her feelings of anger. Indeed, the viewing of the video may have induced a “self Werther effect”. This analysis highlights the urgent need for suicide prevention strategies with specialised and targeted interventions, especially in situations of family conflict. By understanding every aspect of suicidal behaviour, health professionals can implement preventive measures and support systems, while also educating family members to recognise the self-suppressive risk.

Obstructive Sleep Apnea (OSA) is a common disorder affecting both adults and children. It is characterized by repeated episodes of apnea (stopped breathing) and hypopnea (reduced breathing), which result in intermittent hypoxia. We recognize pediatric and adult OSA, and this paper focuses on pediatric OSA. While adults often suffer from daytime sleepiness, children are more likely to develop behavioral abnormalities. Early diagnosis and treatment are important to prevent negative effects on children’s development. Without the treatment, children may be at increased risk of developing high blood pressure or other heart problems. The gold standard for OSA diagnosis is the polysomnography (sleep study) PSG performed at a sleep center. Not only is it an expensive procedure, but it can also be very stressful, especially for children. Patients have to stay at the sleep center during the night. Therefore, screening tools are very important. Multiple studies have shown that OSA screening tools can be based on facial anatomical landmarks. Anatomical landmarks are landmarks located at specific anatomical locations. For the purpose of the screening tool, a specific list of anatomical locations needs to be identified. We are presenting a survey study of the automatic identification of these landmarks on 3D scans of the patient’s head. We are considering and comparing both knowledge-based and AI-based identification techniques, with a focus on the development of the automatic OSA screening tool.

Severe inherited alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic condition linked to chronic obstructive pulmonary disease (COPD). The significance of heterozygous, milder deficiency variants (PiSZ, PiMZ, PiMS) is less clear. We studied AATD genotypes in 145 children (up to 72 months old) with assessed wheezing severity using the Pediatric Respiratory Assessment Measure (BCCH PRAM score). A control group of 74 children without airway obstruction was included. AAT concentration and Pi phenotype were determined from dry blood spot samples using nephelometry and real-time PCR; PiS and PiZ alleles were identified by isoelectrofocusing. Among the wheezers, the Pi*S allele incidence was 2.07% (3 cases) and the Pi*Z allele was 6.9% (10 cases). The Pi*Z allele frequency was higher in wheezers compared to controls (44.8% vs. 20.27%) and the general Lithuanian population (44.8% vs. 13.6%) and was similar to adult COPD patients in Lithuania: Pi*S 10.3% vs. 15.8% and Pi*Z 44.8% vs. 46.1%. No association was found between AAT genotypes and wheezing severity. Finding that wheezer children exhibit a frequency of Z* and S* alleles like that found in adults with COPD suggests a potential genetic predisposition that links early wheezing in children to the development of COPD in adulthood. Larger cohort studies are needed to confirm this finding.

(1) Background: Sleep-disordered breathing and asthma are often interrelated. Children and adults with asthma are more susceptible to sleep apnea. Inhaled corticosteroids effectively reduce inflammation and prevent structural changes in the airways. Objective: to explore the existing literature to determine whether inhaled corticosteroids play a role in sleep-disordered breathing in patients with asthma. (2) Methods: We conducted a thorough search of the PubMed, Scopus, and Web of Science databases for English-language articles published up to 12 May 2024. We utilized the ROBINS-E tool to assess the risk of bias. (4) Conclusions: 136 articles were discerned upon conducting the literature search. A total of 13 articles underwent exhaustive full-text scrutiny, resulting in 6 being considered non-relevant. The remaining seven articles, assessed for eligibility, were incorporated into the final analysis. Five studies were identified in adults and two in children. In adult patients, inhaled corticosteroids, especially at high doses, appear to increase the risk of sleep apnea in a dose-dependent manner. Moreover, the properties of inhaled corticosteroids, such as particle size, may impact the risk of developing sleep apnea. In children, the severity of asthma is a key factor affecting the prevalence of sleep apnea, whereas inhaled corticosteroids appear to be a less significant risk factor compared to adults. All of the studies reviewed were classified as having a high risk of bias or some concerns regarding bias. Each study revealed at least one type of bias that raised notable concerns. This research highlights a complex interaction between the use of inhaled corticosteroids, the severity of asthma, and the onset of sleep apnea. Additional research is necessary to investigate these relationships further.

Background/Objectives: Retinopathy of Prematurity (ROP) remains a leading cause of vision impairment in premature infants, especially those with Respiratory Distress Syndrome (RDS) necessitating respiratory support. This study aimed to identify correlations between plasma levels of Insulin-like Growth Factor 1 (IGF1) and Tumor Necrosis Factor-alpha (TNF-alpha), and the risk of developing ROP. Additionally, it explored the association of ROP severity grades with plasma levels of glucose, lactate dehydrogenase (LDH), creatin phosphokinase (CPK), and other biomarkers, aiming to uncover predictive markers for ROP risk and severity in this population. Methods: This prospective study included premature neonates admitted with RDS requiring respiratory support, conducted over 18 months at the Neonatal Intensive Care Unit of the Louis Turcanu Emergency Clinical Hospital for Children, Timisoara. Plasma levels of IGF1 and TNF-alpha were measured on days 1 and 14 post-birth, alongside the initial assessment of glucose, LDH, and CPK levels. Results: Significant correlations were observed between lower gestational age and elevated LDH levels on day 7–10 (rho = −0.341, p = 0.0123) and between TNF-alpha levels at 2 weeks and ROP severity (rho = 0.512, p = 0.0004). Elevated IGF1 levels were protective against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second, suggesting their potential as biomarkers for ROP risk assessment. Higher levels of TNF-alpha at 2 weeks were associated with an increased risk of ROP (Beta = −0.45, p = 0.0014), whereas higher IGF1 levels offered protective effects against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second. Elevated LDH levels on day 7–10 post-birth were linked to an increased risk of ROP (Beta = 0.29, p = 0.0214). Conclusions: These findings highlight the potential of IGF1 and TNF-alpha as predictive biomarkers for ROP, offering avenues for early intervention and improved management strategies in this high-risk group.

Background: Primary graft dysfunction (PGD) is a form of acute lung injury (ALI) that occurs within 72 h after lung transplantation (LuTx) and is the most common early complication of the procedure. PGD is diagnosed and graded based on the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen and chest X-ray results. PGD grade 3 increases recipient mortality and the chance of chronic lung allograft dysfunction (CLAD). Method: The aim of this retrospective study was to identify new PGD risk factors. The inclusion criteria were met by 59 patients, who all received transplants at the same center between 2010 and 2018. Donor data were taken from records provided by the Polish National Registry of Transplantation and analyzed in three variants: PGD 1–3 vs. PGD 0, PGD 3 vs. PGD 0 and PGD 3 vs. PGD 0–2. Results: A multiple-factor logistic regression model was used to identify decreasing recipient age; higher donor BMI and higher donor central venous pressure (CVP) for the PGD (of the 1–3 grade) risk factor. Conclusions: Longer cold ischemia time (CIT) and higher donor CVP proved to be independent risk factors of PGD 3.

Computed tomography (CT) multi-detector array has been heavily utilized over the past decade. While transforming an individual’s diagnosis, the risk of developing pathogenesis as a result remains a concern. The main aim of this institutional cumulative effective dose (CED) review is to highlight the number of adult individuals with a record of CED ≥ 100 mSv over a time span of 5 years. Further, we aim to roughly estimate both incidence and mortality life-attributable risks (LARs) for the shortlisted individuals. CT studies performed over one year, in one dedicated trauma and emergency facility, were retrospectively retrieved and analyzed. Individuals with historical radiological CED ≥ 100 mSv were short-listed. LARs were defined and established based on organ, age and gender. Out of the 4406 CT studies reviewed, 22 individuals were found with CED ≥ 100 mSv. CED varied amongst the short-listed individuals, with the highest CED registered being 223.0 mSv, for a 57-year-old male, cumulated over an average study interval of 46.3 days. The highest median mortality risk was for females, 214 per 100,000 registered for the age group 51–60 years. While certain clinical indications and diseases require close follow-up using radiological examinations, the benefit-to-risk ratio should be carefully considered, particularly when CT is requested.

Background and objectives: This study aimed to assess the impact and predicted outcomes of patients with multiple trauma by identifying the prevalence of trauma sustained and associated complications. Materials and Methods: This retrospective cohort study focused on individual characteristics of patients with multiple trauma admitted to our County Emergency Hospital. The final table centralized the characteristics of 352 subjects aged between 3 and 93 years who presented with multiple trauma from 2015 to 2021. Inclusion criteria for this study were the presence of multiple trauma, intervention times, mentioned subjects’ ages, and types of multiple trauma. Results: Patients with multiple trauma face an increased risk of mortality due to the underlying pathophysiological response. Factors that can influence the outcomes of multiple-trauma patients include the severity of the initial injury, the number of injuries sustained, and the location of injuries. Conclusion: The first 60 min after trauma, known as the “golden hour,” is crucial in determining patient outcomes. Injuries to the head, neck, and spine are particularly serious and can result in life-threatening complications.

Background: Central Venous Catheter (CVC)-related infections cannot always be solved by replacement, due to some vascular anomalies or an emergency status. This comprehensive, evidence-based review aimed to define the efficacy of antibacterial lock therapy (ALT) compared to the standard of care (SoC) in CVC-related infections. Methods: We performed a systematic search in PubMed, Embase, and Google Scholar, looking for randomized controlled trials (RCTs) and cohort or case-control observational studies. The eligible studies considered the subjects with a diagnosis of CVC-related infections treated with antibacterial lock therapy (ALT) compared to the standard of care (SoC). Results: Among 609 records at the end of the selection process, five articles, referring to observational studies, were included in this systematic review. In pooled analyses, including a total of 276 individuals, microbiological healing (OR 3.78; 95% CI; 2.03–7.03) showed significant differences between ALT and the SoC, with a follow-up varying from 2 weeks to 3 months. Conclusions: Our results suggested that ALT could improve the preservation of CVCs and could be considered when their replacement is not possible as a result of vascular problems. However, only observational studies were included and RCTs are needed to confirm these findings and to increase the level of evidence.

Combined Kelly syndrome, also known as anterior hyperfunction syndrome, is a complex pathological condition of the stomatognathic system, originally established by five characteristics but primarily triggered by edentulism, specifically, the absence of the upper and posterior mandibular teeth. This condition is characterized by a series of clinical features, such as bone loss, tuberosity growth, enamel wear, periodontal damage, muscle fatigue, pain, and temporomandibular joint issues. However, these features are not unique and rather reflect an oral hyperfunction state. There is a lack of consensus on the best way to assess and diagnose this condition, which is proposed to be understood as an “oral hyperfunction state” rather than a syndrome. This study aims to conduct a literature review to analyze the available information on anterior hyperfunction syndrome in dentistry, with the goal of proposing a conceptual model of the etiological risk factors that contribute to early diagnosis and the prevention of complications. This approach has important clinical implications, as it would allow for the early identification and management of risk factors, thus improving the quality of life of patients and preventing malpractice that could compromise their oral health.

Purpose: The aim of this study was to examine the impact of detoxification from prescription opioids on the quality of life (QoL) and pain levels among patients reliant on these medications for chronic pain management. Objective: Long-term use of opioids for pain management may lead to a range of adverse effects, including tolerance, dependence, significant societal costs, and a decline in overall quality of life (QoL). Despite these challenges, there is a limited amount of research focusing on the effects of detoxification and its impact on the QoL for patients with chronic pain tolerant to prescription opioids. Methods: This prospective study included 45 patients who underwent elective detoxification from prescription opioids. Prescription opioids were discontinued during the detoxification treatment in 44 of the 45 cases. QoL was monitored using SF-36v2™ questionnaires administered before detoxification, on the day of discharge, and at least six months after detoxification. Pain levels were assessed using Visual Analogue Scale (VAS) scores before and after the detoxification process. Results: The study was fully completed by 30 patients. At the third SF-36v2™ evaluation, 25 out of 30 patients (83.3%) reported the detoxification treatment as beneficial to their overall health status compared to that before the treatment, and SF-36v2™ questionnaires after detoxification were significantly higher than before the treatment (p < 0.001). A decreased pain level right after the detoxification was reported by 44 of the 45 patients (97.7%), with a significant average reduction of 4.51 points observed (p < 0.001). Conclusions: The observed enhancement in QoL, significant reduction in pain, and cessation of opioid use in most patients with chronic pain tolerant to prescription opioids following opioid detoxification indicate that this method of treatment can be safely and effectively administered and must be considered for chronic pain patients.

Background: This study aimed to examine whether individuals with chronic tinnitus report more positive experiences following internet-based cognitive behavioral therapy (CBT). Methods: A mixed-methods design was used, nested in clinical trials evaluating internet interventions for tinnitus. Participants (n = 164) completed online questionnaires (both structured and open-ended) providing demographic information as well as health variables (e.g., tinnitus distress, anxiety, depression, insomnia). An open-ended question listing positive effects or outcomes related to having tinnitus was also included. Responses to the open-ended questions were analyzed using qualitative content analysis. Results: Of the 164 eligible participants, 32.3% (n = 53) provided at least 1 positive experience both at pre- and post-intervention, with 9.1% (n = 19) providing positive experiences only at pre-intervention, 49 (29.9%) providing positive experiences only at post-intervention, and 28.7% (n = 47) of the participants did not provide any positive experiences on either measurement occasion. Significantly more positive experiences were reported following the intervention in the overall sample (p < 0.0001, paired sample t-test). In addition, participants who reported positive experiences in both pre- and post-intervention also reported more positive experiences following intervention (p = 0.008, paired sample t-test). Conclusions: Internet-based CBT can help individuals with tinnitus to think more positively by changing unhelpful thought patterns. Open-ended questions can supplement structured questionnaires to measure treatment outcomes.

Background: The prognostic significance of liver dysfunction in COVID-19 patients remains unclear. In this study, we investigated the association between liver function test results and severe disease progression in COVID-19 patients. Methods: This retrospective study included consecutive Japanese COVID-19 patients admitted between February 2020 and July 2021. Predictive variables for severe disease progression were identified by multivariate logistic regression analysis. Severe disease-free survival was estimated with the Kaplan–Meier method and Cox regression analysis. Aspartate aminotransferase (AST) was divided into three grades: grade 1, AST < 30 U/L; grade 2, 30 U/L ≤ AST < 60 U/L; and grade 3, AST > 60 U/L. Results: Among 604 symptomatic patients, 141 (23.3%) developed severe disease at a median of 2 days postadmission. The median hospital stay was 10 days, and 43 patients (7.1%) died during hospitalization. Multivariate regression analysis revealed that hypertension, decreased lymphocyte count, and elevated LDH, CRP, and AST levels (grade 2 and grade 3 relative to grade 1) were the significant predictive variables. Severe disease-free survival time was significantly different between the different AST grades (hazard ratio (HR): grade 2 vs. grade 1, 4.07 (95% confidential interval (CI): 2.06–8.03); grade 3 vs. grade 1, 7.66 (95% CI: 3.89–15.1)). Conclusions: The AST level at admission was an independent risk factor for severe disease in hospitalized Japanese patients with COVID-19.

BACKGROUND: Age contributes to body composition alteration, rises a common disorder in elderly known as sarcopenic obesity (SO), which is characterized by the combination of obesity (excess fat mass) and sarcopenia (reduced skeletal muscle mass) clinical form and function. CONTENT: The primary cause of SO is insulin resistance. Glucose transporter 4 (GLUT4) dysfunction results in impaired fatty acids oxidation. Decreased muscle mass results in lower mitochondria number and volume. Both will increase oxidative stress. Together with altered myokines in SO, oxidative stress was promoted and lead to higher M1 macrophages and failure in autophagy. The pro-inflammatory condition and dysbiosis links SO to a variety of cardiometabolic conditions, including non-alcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease. The mortality, comorbidities, cardiometabolic diseases, and disability or impairment of SO is higher compare to obesity or sarcopenia alone. Some treatments have been developed for SO including adequate dietary intake, vitamin D and antioxidant supplementation, and exercises. SUMMARY: SO is more prevalent among the elderly and has a significant negative impact on their quality of life. Therefore, maintaining muscle mass and strength as well as preventing obesity should be the key goals of initiatives to support healthy aging. KEYWORDS: aging, body composition, obesity, sarcopenia, skeletal muscle, metabolic syndrome

BACKGROUND: Previous research has demonstrated the effect of Elephantopus scaber Linn. leaf extract (ESLE) on various cancer cell lines. However, research on the effects of ESLE on oral squamous cell carcinoma (OSCC), especially tongue cancer, is still lacking. Moreover, the apoptotic mechanisms induced by ESLE are not well understood and require further exploration. Therefore, this study was conducted to investigate the effects of ESLE on cell viability and apoptosis in human squamous cell carcinoma (HSC)-3 tongue cancer cells. METHODS: HSC-3 cells were treated with varying concentrations of ESLE, doxorubicin, and a combination of both. Cell viability and apoptosis were assessed using MTT and Sub-G1 assays. The expression levels of survivin and its phosphorylated form at threonine (Thr)34 were evaluated using Western blot analysis. RESULTS: ESLE exhibited a concentration-dependent cytotoxic effect on HSC-3 cells in decreasing cell viability (Kruskal Wallis, p=0.001) and increasing apoptotic cells (ANOVA, p=0.001) significantly. When combined with doxorubicin, ESLE further enhanced the induction of apoptosis compared with doxorubicin alone. The combined treatment resulted in a decrease in the levels of phosphorylated survivin (p-Surv) Thr34, indicating the inhibition of survivin's anti-apoptotic function. CONCLUSION: ESLE significantly enhances the efficacy of doxorubicin, thereby sensitizing its ability to induce apoptosis in HSC-3 tongue cancer cells. This sensitization occurs through the inhibition of survivin activity, particularly at the Thr34 phosphorylation site. These findings suggest that ESLE could serve as a potential adjuvant to improve the effectiveness of doxorubicin in inducing apoptosis in tongue cancer cells. KEYWORDS: Elephantopus scaber, doxorubicin, tongue cancer, HSC-3 cells, apoptosis, Survivin, Thr34 phosphorylation

BACKGROUND: SPRY4 intronic transcript 1 (SPRY4-IT1), is a long non-coding RNA coded by the intron of SPRY4. SPRY4 is highly expressed in gastrointestinal stromal tumor (GIST) and inhibits the tumorigenesis of GIST, but whether SPRY4-IT1 regulates the tumorigenesis of GIST or not remains unclear. Therefore, in this study, the regulation of SPRY4-IT1 expression and its role in GIST will be investigated. METHODS: GIST-T1 cells, and Ba/F3 cells which express KIT proto-oncogene (KIT) and SPRY4-IT1 were used as cell models. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to examine mRNA expression, while the protein expression and signal transduction were examined by western blot. The association between SPRY4-IT1 and KIT was examined by pull down of KIT and PCR. Cell proliferation, survival, and cell cycle progression were examined by cell counting kit-8 (CCK8) and flow cytometry. RESULTS: KIT mutants increased the expression of SPRY4-IT1 in GIST. SPRY4-IT1 bound to KIT, also enhanced the activation and expression of both wild-type KIT and primary KIT mutants, therefore increasing the activation of downstream signaling proteins AKT and ERK of KIT, GIST cell survival, and proliferation. In addition, SPRY4-IT1 reduced the sensitivity of wild-type KIT, or primary KIT mutants to the first-line targeted therapeutic drug of GIST, imatinib, which can inhibit KIT activation. Gaining drug-resistant secondary KIT mutants might be one of the main reasons of GIST recurrence after targeted therapy. Similar to wild-type KIT and primary KIT mutants, the activation and expression of secondary KIT mutants and their resistance to imatinib were also increased by SPRY4-IT1. CONCLUSION: The results indicated positive feedback between SPRY4-IT1 and wild-type KIT, primary KIT mutants or secondary KIT mutants, and the upregulation of AKT and ERK activation by SPRY4-IT1 in GIST cells, providing a new insight in the KIT signaling regulation in GIST, and the resistance of GIST to targeted therapy. KEYWORDS: SPRY4-IT1, KIT, GIST, SPRY4, signaling

BACKGROUND: Chronic exposure of high glucose (HG) in endothelial cell induces senescence which may contribute to the development and progression of age-related diseases including insulin resistance. Andrographis paniculata improves insulin resistance in recent in vitro and in vivo studies. Anti-inflammatory and antioxidant properties of A. paniculata may be the new therapeutic approach to inhibiting premature senescence. However, the senolytic effect of A. paniculata on endothelial cells has not been investigated comprehensively. This study was conducted to evaluate the effect of A. paniculata extract on HG-induced endothelial cell senescence and the underlying mechanisms. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with 33 mM HG and 7.5 μg/mL A. paniculata extract for 48 hours. The expressions of p16, p21, interleukin (IL)-6, IL-8, insulin receptor substrate (IRS)-1, mammalian target of rapamycin, and sirtuin 1 (SIRT1) were measured by performing real-time quantitative polymerase chain reaction (RT-qPCR). The senescence-associated-β-galactosidase (SA-β-gal) staining was performed to observe the positive-stained senescent cells, while the cell surface expression of IL-1α was examined with flow cytometry method. RESULTS: A. paniculata extract reversed senescence in HUVECs under HG conditions by reducing mRNA expressions of p16 and p21, the number of SA-β-gal-positive-stained cells, and the expression of IL-1α on cell surface, which decreased the activation of IL-6 and IL-8. In addition, A. paniculata extract decreased the mRNA expression of mTOR and increased the mRNA expressions of IRS-1 as well as SIRT1. CONCLUSION: A. paniculata extract ameliorated senescence and improved insulin sensitivity by regulating the mTOR, SIRT1, and IRS-1 mRNA expressions on HG-treated HUVECs. KEYWORDS: Andrographis paniculata, endothelial cell, senescence, high glucose, nutrient-sensing pathways

BACKGROUND: Dyslipidemia derives from disturbances in lipid metabolism as an interaction between genetic and environmental factors, characterized by increased levels of cholesterol, triglycerides, low-density lipoprotein (LDL) and decreased levels of high-density lipoprotein (HDL). Continuous dyslipidemia will increase the risk of atherosclerosis. In dyslipidemia, macrophages release inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-12, IL-15, IL-18, and then induce T-cell infiltration formed atherosclerotic plaques. Beet (Beta vulgaris L.) which contains active compounds and antioxidant, such as flavonoids and betacyanin, has the ability to reduce dyslipidemia. This study evaluated effect of beetroot juice and beetroot extract on dyslipidemic rat models by evaluating the level of HDL, LDL and IL-6. METHODS: Fourty-two male Sprague Dawley rats were divided into seven groups. Rats were fed either with standard food or high fat diet (HFD) for 28 days, then different interventions using either single combination of simvastatin, beetroot juice, or beetroot extract were given alongside the standard food or HFD diet for another 28 days. LDL and HDL were measured pre- and post-intervention, while IL-6 was measured only post-treatment. RESULTS: Daily administration of a single beetroot juice or beetroot extract or in combination with simvastatin reduced LDL significantly compared to pre-intervention. The interventions also increased HDL significantly and lower IL-6 concentrations compared to group that received no intervention. CONCLUSION: Administration of beetroot juice and beetroot extract can lower LDL, increase HDL, and decrease IL-6 either alone or in combination treatment with simvastatin, it is indicated beetroot have a potential benefit for prevention and therapeutic in dyslipidemia. KEYWORDS: beetroot juice, beetroot extract, LDL, HDL, IL-6

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disease affecting neuromuscular junction involvement. The finding that T-reg level in MG patients was lower than that in normal persons leads to the idea that the primary pathology of the disease is T-reg dependent. The T-reg level of MG patients seems to be decreasing compared to that of normal persons. The study was conducted to observe the contribution of T-reg level in plasma injected into Swiss-Webster mice to develop clinically and pathologically myasthenic syndromes. METHODS: Swiss-Webster mice were grouped into three groups: the groups received plasma with normal, low, and high T-reg levels, respectively. The T-reg levels of the mice were measured with flow cytometry analysis and a human regulatory T-cell cocktail for T-cell surface cell marker. The motor function, interleukin (IL)-2, interferon (IFN)-γ, and thymus weight of mice were measured after the injection. Histopathological examination was performed to analyze mice’s muscles and thymus. RESULTS: The result identified that the motor function (2-week treatment group: p=0.021 and 3-week treatment group: p=0.032) and muscle width (p=0.014, p=0.032 and p≤0.001) were significantly lower in the low T-reg level plasma group compared to control and high T-reg level plasma groups. The thymus showed an increase in weight without an increase in the cortex-medulla ratio of the thymus, indicating hyperplasia. Both IL-2 and IFN-γ levels were lower in the low and high T-reg level groups compared with the control group, indicating the autoimmune process. CONCLUSION: Low T-reg level was associated with lower motor function, muscle width, increased thymus weight, as well as lower IL-2 and IFN-γ levels. T-reg level contributed to clinical myasthenic syndromes but not pathological findings. This research method is expected to be a basis for the development of animal models with Swiss-Webster mice. KEYWORDS: animal model, Myasthenia gravis, Swiss-Webster mice

BACKGROUND: Probiotics may modify the gut microbiome and have been proven to improve psoriasis vulgaris. Lactiplantibacillus plantarum IS-10506 is a probiotic strain of Indonesian origin. It offers a safe and effective probiotic for psoriasis patients in Indonesia. This study was conducted to evaluate the effect of L. plantarum IS-10506 on clinical and immunology markers in psoriasis vulgaris. METHODS: This randomized, placebo-controlled, and double-blind trial compared L. plantarum IS-10506 (2×1010 CFU/day) and placebo in 49 patients mild-moderate psoriasis vulgaris, which were divided into intervention (n=24) and control groups (n=25). The interventions were given twice daily for 12 weeks. Both groups received topical corticosteroid and emollient as standard treatment. Psoriasis area and severity index (PASI), dermatology life quality index (DLQI), interleukin (IL)-10, IL-17, and forkhead box protein (Foxp3) were then assessed. RESULTS: Mean PASI score for the the subjects in probiotic group was significantly reduced compared to placebo at week-6 (p=0.024), and was sustained until week-12 (p=0.049). At week-12, DLQI scores in the probiotic group were lower than placebo (7.57±5.77 vs. 7.79±5.48). IL-17 level was significantly decreased (p=0.013), while the IL-10 and Foxp3 were significantly increased (p≤0.001 and p=0.048, respectively) in probiotic group. Six months after the completion of study, subjects in probiotic group had a lower probability of flares (52.2%) compared to placebo (79.2%). Two subjects receiving probiotics and one receiving placebo noticed changes in defecation frequency, while another subject in the placebo group complained of mild nausea. CONCLUSION: L. plantarum IS-10506 might effectively improve clinical outcomes and immune biomarkers in psoriasis vulgaris patients, potentially acting as an adjuvant therapy. KEYWORDS: psoriasis, probiotic, clinical severity, immune marker, human and health

BACKGROUND: Monitoring platelet count and related indices is crucial for managing hematological disorders. No studies are reporting normal platelet indices in the adult Indonesian population. Therefore, this study was conducted to establish normal reference values for platelet count and indices in a healthy population in Indonesia and investigate their association with platelet count and each parameter. METHODS: This cross-sectional study included healthy adults from both sexes who underwent hematological testing in our laboratory. Two mL of venous blood was drawn and analyzed using an automated machine ADVIA 2120 to identify platelet count, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), mean platelet component (MPC), platelet component distribution width (PCDW), mean platelet mass (MPM), platelet mass distribution width (PMDW), and large platelet count. RESULTS: This study included 1037 subjects with median of 27 (18–58) years old. Normal reference range values for platelet indices in adult Indonesians was established, which was significantly different between males and females (p

BACKGROUND: Preeclampsia management is necessary, as it is one of the leading causes of death during pregnancy. Exosomal microRNAs (miRNAs) can serve as biomarkers for early detection, diagnosis, and prognosis of preeclampsia. NanoStrings is an effective method for identifying exosomal miRNA due to their high sensitivity and ability to work with small amounts of miRNA; however, the analysis using this method for determining preeclampsia biomarker is still limited. Therefore, this study was conducted to utilize the NanoStrings method in identifying preeclampsia biomarkers related to its underlying pathophysiology. METHODS: This study involved 12 pregnant women at 20–40 weeks of gestation, including 6 preeclampsia women and 6 normotension women. The miRNAs from plasma exosomes were processed using NanoStrings method with NanoString nCounter SPRINT Profiler. Enrichment analysis of The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways were performed to examine the pathophysiological pathways of preeclampsia, using the DIANA–miRPath v3.0. RESULTS: Forty-eight miRNAs were downregulated and 7 were upregulated (miR-1283, miR-613, miR-520a-3p, miR-3185, miR-556-3p, miR-1973, and miR-598-3p) in women with preeclampsia. The highest expression was observed in miR-1283 (log fold-change: 3.69) and the most lowest expression was in miR-152-3p (log fold-change: 1.41). Enrichment analysis showed that the most upregulated miRNAs pathways was estrogen signaling pathway, and the most downregulated was Hippo signaling pathways. CONCLUSION: miR-1283 has the highest expression, while and miR-152-3p has the lowest expression in preeclampsia women. These miRNAs are shown to be linked to specific pathways, shedding light on the pathophysiology of preeclampsia, and may serve as promising biomarkers. KEYWORDS: exosomes, biomarker, miRNAs, pathophysiology, preeclampsia, pregnancy

BACKGROUND: The burden of disease due to lead exposure continues to increase. Lead interferes with 25(OH)D hydroxylation and calcium transport, increasing osteoclastic activity and bone resorption. Pyridinoline crosslinks (PYD), as an indicator of bone damage, can be seen earlier compared to imaging changes. Therefore, it is necessary to determine the correlation between serum 25(OH)D levels and the urinary PYD/creatinine ratio in workers exposed to lead, since up to now, there are only limited studies related to it. METHODS: This cross-sectional study involved 104 workers exposed to lead, selected from parents whose children had blood lead levels above 10 µg/dL. Questionnaires and physical examination were performed to obtain characteristic data from subjects. Data regarding blood lead levels, serum 25(OH)D levels, urinary PYD levels, and urinary creatinine levels were also obtained from various laboratory methods. RESULTS: Most subjects (86.5%) had inadequate serum 25(OH)D. Median blood lead levels was 6.3 (1.2-35.5) µg/dL, chronic lead exposure index was 35.3 (1.2-535.8) years µg/dL, serum 25(OH)D levels was 22 (8-52) ng/mL, and urinary PYD/creatinine ratio was 5.3 (3.6-28.1)×10-6. There was a significant negative correlation between serum 25(OH)D levels and urinary PYD/creatinine ratio in workers exposed to lead. There was also a significant positive correlation between chronic lead exposure index and the urinary PYD/creatinine ratio. CONCLUSION: Since urinary PYD/creatinine ratio is correlated with serum chronic lead exposure index and serum 25(OH)D levels, it suggests that pyridinoline might be a potential biomarker to detect bone metabolism disorder due to the chronic lead exposure. Vitamin D adequacy is also an important factor in preventing bone metabolism disorder amidst chronic lead exposure. KEYWORDS: 25(OH)D, bone resorption, pyridinoline, lead, worker

Pouchitis, as the most common complication after ileal pouch-anal anastomosis (IPAA), has an incidence from 7% to 46%. Pouchitis treatment still represents one of the biggest gaps of knowledge in the treatment of diseases. This review has focused on achievements and challenges in the treatment of pouchitis. A combined assessment of symptoms, endoscopic findings, histologic results, quick biomarkers, and fecal calprotectin test were determined to be valuable diagnostic criteria. Conventional therapy was described as a modification of bacterial flora, mainly with antibiotics and more recently with probiotics such as bifidobacteria, lactobacilli, and streptococci. Other therapeutic approaches such as anti-tumor necrosis factor, infliximab, adalimumab, vedolizumab, ustekinumab, tacrolimus, tofacitinib, thiopurines, corticosteroids, prolyl hydroxylase–containing enzymes, povidone-iodine, dextrose spray, fecal microbiota transplantation, herbal medicines, and leukocyte apheresis have been discussed. Changes in dietary components, and administration of complementary and alternative medicine, probiotics, and fecal transplantation in addition to conventional therapies were also shown to affect the outcome of disease. Due to the potential significant impairment in quality of life caused by pouchitis, it is essential to address the gaps in knowledge for both patients and physicians in its treatment. Therefore, well-designed and adequately powered studies should assess the optimal treatment for pouchitis.

Background: Sinistral portal hypertension (SPH) is the only type of portal hypertension that is entirely curable. However, it can easily cause varicose veins in the esophagus and/or stomach, as well as upper gastrointestinal hemorrhage. This study aimed to investigate the clinical characteristics and treatments of sinistral portal hypertension. Methods: All patients with pancreatic disease were included in this retrospective cohort study at the Affiliated Hospital of Southwest Medical University (Luzhou, China) from September 2019 to September 2021. The required information including the patient’s demographics, serum laboratory indicators, imaging and endoscopy examinations, and clinical features were gathered and evaluated. The results were expressed as numbers and percentages.Results: Out of the 830 patients with pancreatic diseases, 61 (7.3%) developed SPH. The most common cause of SPH was acute pancreatitis (80.3%), followed by chronic pancreatitis (11.5%). The splenic vein was the most frequently affected vein in patients (45/61, 73.8%). The findings of the contrast-enhanced computed tomography (CECT) indicated that 51 cases (83.6%) had gastric fundal-body varices, and three cases had combined gastric and esophageal varices. In the perigastric collateral channel formation, gastroepiploic varices (43/61, 70.5%) most frequently occurred in patients with SPH. Splenomegaly was a prevalent manifestation in SPH patients (45.9%). Five cases had gastrointestinal variceal hemorrhage.Conclusion: SPH was associated with the patency of the splenic vein and the formation of distinctive perigastric collateral veins. Surgery and/or endoscopic treatment were recommended, particularly for patients who have experienced a significant amount of gastrointestinal bleeding and have failed conservative treatment.

Background: Guillain-Barre Syndrome (GBS) is the most prevalent acute peripheral polyneuropathy disorder. The disparities between populations and variations in the major risk factors highlight the importance of country-specific studies. This study aimed to report clinical characteristics and outcomes of ICU-admitted patients with GBS in an academic medical center in Iran. Methods: The data were collected retrospectively from all patients with GBS admitted to Namazi Hospital, affiliated with Shiraz University of Medical Sciences, (Shiraz, Iran), between March 2016 to March 2021. Specialized neurological information and the Acute Physiology and Chronic Health Evaluation (APACHE II) score were recorded. The SPSS software was used to analyze the data. The analyzed data were reported as numbers and percentages, or mean±SD, or median(Interquartile) Results: The study included 132 GBS patients, with an average age of 47.87±15.4 years and a male-to-female ratio of 1.69:1. More than half of the patients (58.5%) were classified as having an axonal disease. In patients with axonal illness, 51.4% of patients had lower limb powers

Background: Sepsis is still one of the leading causes of mortality and morbidity in children worldwide. Consumptive coagulopathy and suppression of thrombopoiesis in the bone marrow resulting from immune dysregulation are pathological mechanisms that cause thrombocytopenia in sepsis. Platelet count (PLT) and indices, such as mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) are markers of platelet activation and are strongly influenced by platelet morphology and proliferation kinetics. We aimed to study the use of platelet count and indices as predictors of mortality in children with sepsis.Methods: This is a cross-sectional study of 45 children diagnosed with sepsis on admission at Haji Adam Malik Hospital, Medan, North Sumatra, Indonesia, between October and November 2022. Blood samples were drawn upon admission, and platelet count and indices were then determined for all children. Subjects were followed up till discharge from hospital or death. Receiver Operating Characteristic (ROC) curve analysis of platelet parameters was done to determine the area under the curve (AUC), optimal cut-off value, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in predicting mortality in children with sepsis. Using the cut-off values from ROC curve analysis, the odds ratio with 95% confidence interval was calculated using multiple logistic regression analyses. A P value less than 0.05 was considered statistically significant.Results: MPV, PDW, and PDW/PLT were significantly higher in non-survivors than survivors (P=0.04, P=0.02, and P=0.04, respectively). ROC curve analysis showed that PDW had the largest AUC (0.708 [95% CI=0.549–0.866]) with a cut-off value of 14.1%, sensitivity of 63.6%, and specificity of 82.6%. PDW was also the only parameter that significantly affected the outcome of children with sepsis. PDW≥14.1% at admission increases the risk of mortality by 5.7 times.Conclusion: Admission PDW is a fast and specific tool to predict the outcome of children with sepsis.

Background: Ovarian granulosa cells (GCs) are essential for follicular development. Ovarian advanced glycation end-products (AGEs) accumulation is related to GCs dysfunction. Alpha-lipoic acid (ALA) illustrates therapeutic capabilities for infertility-related disorders. Therefore, this study assessed the effects of ALA on AGEs-induced GCs hormonal dysfunction.Methods: The study was conducted from October 2021 to September 2022 at the Department of Medical Genetics, Shiraz University of Medical Sciences. Isolated GCs (n=50) were divided into control, human glycated albumin (HGA), HGA+ALA, and ALA treatments. Steroidogenic enzymes and AGE receptor (RAGE) genes were assessed by qRT-PCR. Steroid hormones and RAGE protein were evaluated using ELISA and Western blotting. Data were analyzed using GraphPad Prism software (ver. 9), and P

Background: Odontogenic cysts and tumors develop from the dental follicle of asymptomatic impacted teeth. Odontogenic tissues express the epidermal growth factor receptor family (EGFR), which mediates cell proliferation, survival, and neoplastic differentiation. The present study aimed to compare the immunohistochemical expression of EGFR and human epidermal growth factor receptor 2 (HER2) in the dental follicle of impacted wisdom teeth with normal and abnormal radiographic size.Methods: In this analytical study, immunohistochemical staining of EGFR and HER2 was performed on 30 normal and 30 abnormal follicles of impacted third molars. Follicles with a width of

Purpose: This research and analysis seek to determine the frequency and total number of miscarriages among women of reproductive age over a span of six years in MBAL "NiaMed", locally and globally. Material/Methods: In an observational study, researchers collected data from scientific articles and workplace sources to investigate miscarriages. The study concentrated on women of reproductive age who had experienced pregnancy-related issues, with all information derived from scientific literature and medical records. Results: Both locally and globally, the incidence of spontaneous abortions remains high despite advances in medical prophylaxis and prevention of reproductive failures. The rates per 1,000 women are 53.7 in Russia, 33 in Mexico, and 11.9 in Bulgaria. This is compared with the local incidence at MBAL "NiaMed" among women who have had two or more miscarriages. Conclusion: Miscarriages represent a major global health concern, impacting millions of women annually. Identifying risk factors and implementing effective interventions can decrease miscarriage rates and enhance pregnancy outcomes. Essential components of a comprehensive strategy to tackle this issue include public health initiatives, better access to healthcare services, and ongoing research into potential treatments.

Objective (s): Considering the role of self-care in reducing the burden of non-communicable diseases and in order to properly increase the importance of health to society, paying attention to the self-care is a priority. This study was conducted with the aim of investigating the effect of an educational intervention in the context of social messengers on the awareness of the health workers regarding the self-care program. Methods: This semi-experimental study was conducted on 705 employees (doctors, nurses, midwives, health care workers) of health centers in Ilam province, Iran during 2020 and 2021. To collect data, a self-designed questionnaire containing 330 questions related to the 22 educational packages of the national self-care program provided by the Ministry of Health was used. The questionnaire was completed before an educational intervention and 9-months follow-up. The data was analyzed with SPSS version 24 software and through paired t-test and chi-square test. Results: The results indicated a significant increase in the awareness of health workers in the field of self-care program during a period of nine months after the educational intervention using the virtual educational method. A statistically significant relationship was observed between increasing the level of awareness of health workers with variables such as age (0.01), education level (0.05), gender (0.01) and organizational position (0.01). Conclusion: Considering the important and fundamental role of health workers in improving the level of health literacy of the society and on the other hand the growing trend of access to social messengers, it is suggested with a cascade approach and based on social accountability, suitable educational programs to improve the awareness of health workers and subsequently health ambassadors at the household level should be prioritized.

Objective(s): Convulsions caused by fever in children and parents not knowing about the nature of this disease cause severe anxiety and inappropriate performance in parents. Due to the cost-effectiveness of the telenursing method, nurses can use it to provide a large amount of information in a short period with distance education. Therefore, the present study was conducted with the aim of determining the effect of telenursing training on the anxiety of mothers with children suffering from febrile convulsions. Methods: This quasi-experimental intervention study was conducted in 2020-2021 among 60 mothers with children suffering from febrile seizures in the hospitals of Birjand, Iran. The sampling method was accessible and then people were randomly divided into two intervention and control groups. After being discharged from the hospital, the intervention group received telenursing (for 2 weeks and 3 sessions each week for 15 minutes via mobile phone and by calling the mothers and sending an educational video). The control group received routine training at discharge. The data collection questionnaire included the demographic and background information and the Spielberger anxiety questionnaire. The Spielberger questionnaire was completed at the beginning and after the end of the intervention. SPSS software version 16 and paired t, independent t and chi-square statistical tests were used for data analysis. Results: Stait and trait anxiety before the intervention was not significant between the control and intervention groups (P=0.865 and P=0.153, respectively). There was a statistically significant difference between the two intervention and control groups in Stait and trait anxiety after the intervention, and it was reduced in the intervention group (P

Objective(s): Health tourism is a branch of the tourism industry that is of interest to many countries of the world due to its high demand and good income. Therefore, considering the importance of health tourism and the existing potential in Mazandaran province, this study was conducted with the aim of identifying and analyzing the factors affecting the development of the health tourism industry in Mazandaran province. Methods: The present study was conducted using a qualitative method with a content analysis approach. For this purpose, 17 health tourism industry experts and health tourists were selected using the purposeful sampling method. Semi-structured interviews were used to collect data. The interviews were conducted until we reached a point of theoretical data saturation. Results: The findings showed that the health tourism industry in Mazandaran province is affected by structural, process and contextual factors. The structural factors included issues related to infrastructures, potentials/attractions, institutional factors, and expert human resources for health tourism destination. The process factor included issues related to drivers of health tourism, provision of health services and destination situational factors. The contextual-field factor included issues related to sociocultural contexts, potentials and attractiveness of tourism, and economic capacity. Conclusion: Despite the importance of services related to health tourism and considering the increasing demand of this industry, travelers who travel to Mazandaran province need a variety of services, and the need to pay attention to quality service development in tourism destinations is evident. Therefore, the provision of other essentials for health tourists such as infrastructure, destination attractions, financial capacities, sociocultural conditions, human resources, situational factors are the requirements for the development of this industry.

Objective(s): One of the most common problems of nursing students in the clinical environment and Objective Structured Clinical Examination (OSCE), is anxiety and lack of accuracy, which can lead to negative effects on their learning and performance. Considering the simplicity and cost-effectiveness of aromatherapy, the present study aims to the effect of lavender aromatherapy on the accuracy, exam anxiety, and performance of nursing students in OSCE. Methods: This clinical trial study was conducted on 60 undergraduate nursing students under the OSCE in 2022. Eligible students who met inclusion criteria were recruited by convenience sampling and then were allocated randomly with the random sequence generation software, to intervention (n=30) and control groups (n=30). The intervention included aromatherapy with lavender essential oil with 100% purity for 10 minutes. Toulouse- Pieron Attention questionnaire, Sarason's test anxiety, and performance checklist were used in this study. Data were analyzed using descriptive and inferential statistical methods by SPSS version 26 statistical software. Results: The results indicated a significant decrease in the average exam anxiety score with P = 0.03 and a significant improvement in accuracy with P < 0.001 after aromatherapy in the intervention group. Also, the results of the independent t-test showed that after the intervention, there was a significant difference in the average exam anxiety score with P = 0.02 and accuracy with P < 0.001 between the intervention and control groups. Meanwhile, the average performance score of the students' grades was not significant between the two groups. Conclusion: Considering the positive effects of inhaling the scent of lavender in improving the accuracy and reducing the anxiety of the nursing students' exam, the use of this low-cost program, with easy access and without complications, is recommended along with other methods.