Objective:To investigate the causal relationship between type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), body mass index (BMI) and papillary thyroid cancer using Mendelian randomization(MR) study.Methods:Publicly available genome-wide association studies (GWAS) were used as the data source to screen single nucleotide polymorphisms significantly associated with exposure factors (instrumental variables), and the inverse variance weighting (IVW), weighted median, MR-Egger analysis, simple mode, and weighted mode of two-sample MR were used to assess the causal association between T2DM, T1DM, BMI and papillary thyroid cancer. The reliability and stability of the results were assessed by heterogeneity analysis, multiple validity analysis and sensitivity analysis.Results:A total of 118 strong instrumental variables for T2DM, 76 for T1DM, and 486 for BMI were screened respectively to conduct two-sample MR analysis. Among the 5 MR analysis methods, the results of the IVW method showed that T2DM was significantly associated with papillary thyroid cancer (odds ratio ( OR)=1.147, 95% CI: 1.026-1.282; P=0.016), and the genetic effect values ( β values) of the other 4 analysis methods and IVW method were in the same direction; the results of heterogeneity analysis, multiplicity analysis and sensitivity analysis showed all P>0.05. T1DM (IVW method: OR=1.000, 95% CI: 0.952-1.051; P=0.994) and papillary thyroid cancer, BMI (IVW method: OR=1.214, 95% CI: 0.923-1.598; P=0.166) and papillary thyroid cancer were not clearly causally related. Conclusions:There is a causal association between T2DM and papillary thyroid cancer, and T2DM increases the risk of papillary thyroid cancer. There is no clear causal association between T1DM, BMI and papillary thyroid cancer.

Radiation-induced rectal injury (RRI) refers to inflammatory intestinal complications of patients with pelvic cavity, abdominal cavity and retroperitoneal tumor during or after radiotherapy, presenting symptoms such as diarrhea, abdominal pain, anal distension, bloody stool, etc. In severe cases, rectovaginal fistula, intestinal obstruction, canceration can occur, adversely affecting the quality of life of patients. The clinical factors of RRI involve total radiotherapy dose, tumor volume, radiotherapy mode and patient-related risk factors. The diagnosis mainly depends on imaging examinations (such as CT, MRI and ultrasound), endoscopy and laboratory examination. The mechanism of RRI is related to intestinal epithelial cell destruction, stem cell injury, microvascular changes and microbial flora imbalance. At present, there is no gold standard for RRI treatment, and the main measures include surgical treatment, internal medicine treatment, hyperbaric oxygen therapy and fecal microbiota transplantation, etc. In this article, the latest progress in the pathogenesis, diagnosis and treatment of RRI was reviewed.

Human immunodeficiency virus(HIV)is the pathogen of acquired immune deficiency syndrome(AIDS).The vi-rus is a highly contagious and highly pathogenic disease caused by the virus attacking the human immune system,which remains a ma-jor global public health problem.Interferon(IFN)is a key cytokine with antiviral and cell-regulatory properties,involved in functions such as cell proliferation,innate and adaptive immune responses.The JAK/STAT signaling pathway is a signal transduction pathway stimulated by cytokines that is involved in many important biological processes such as cell proliferation,differentiation,apoptosis,and immune regulation.With the further in-depth research on AIDS,it has been revealed that IFN and the JAK/STAT pathway play crucial roles in the activation and replication of HIV-1 in target cells.This paper summarizes the structure,signal transduction,and regulatory mechanisms of IFN and the JAK/STAT pathway,and explores the mechanism of IFN-regulated JAK/STAT signaling path-way in HIV-1.It is expected to provide new treatment strategies for the clinical treatment of AIDS.

Objective:To investigate the causal relationship between type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), body mass index (BMI) and papillary thyroid cancer using Mendelian randomization(MR) study.Methods:Publicly available genome-wide association studies (GWAS) were used as the data source to screen single nucleotide polymorphisms significantly associated with exposure factors (instrumental variables), and the inverse variance weighting (IVW), weighted median, MR-Egger analysis, simple mode, and weighted mode of two-sample MR were used to assess the causal association between T2DM, T1DM, BMI and papillary thyroid cancer. The reliability and stability of the results were assessed by heterogeneity analysis, multiple validity analysis and sensitivity analysis.Results:A total of 118 strong instrumental variables for T2DM, 76 for T1DM, and 486 for BMI were screened respectively to conduct two-sample MR analysis. Among the 5 MR analysis methods, the results of the IVW method showed that T2DM was significantly associated with papillary thyroid cancer (odds ratio ( OR)=1.147, 95% CI: 1.026-1.282; P=0.016), and the genetic effect values ( β values) of the other 4 analysis methods and IVW method were in the same direction; the results of heterogeneity analysis, multiplicity analysis and sensitivity analysis showed all P>0.05. T1DM (IVW method: OR=1.000, 95% CI: 0.952-1.051; P=0.994) and papillary thyroid cancer, BMI (IVW method: OR=1.214, 95% CI: 0.923-1.598; P=0.166) and papillary thyroid cancer were not clearly causally related. Conclusions:There is a causal association between T2DM and papillary thyroid cancer, and T2DM increases the risk of papillary thyroid cancer. There is no clear causal association between T1DM, BMI and papillary thyroid cancer.

Human immunodeficiency virus(HIV)is the pathogen of acquired immune deficiency syndrome(AIDS).The vi-rus is a highly contagious and highly pathogenic disease caused by the virus attacking the human immune system,which remains a ma-jor global public health problem.Interferon(IFN)is a key cytokine with antiviral and cell-regulatory properties,involved in functions such as cell proliferation,innate and adaptive immune responses.The JAK/STAT signaling pathway is a signal transduction pathway stimulated by cytokines that is involved in many important biological processes such as cell proliferation,differentiation,apoptosis,and immune regulation.With the further in-depth research on AIDS,it has been revealed that IFN and the JAK/STAT pathway play crucial roles in the activation and replication of HIV-1 in target cells.This paper summarizes the structure,signal transduction,and regulatory mechanisms of IFN and the JAK/STAT pathway,and explores the mechanism of IFN-regulated JAK/STAT signaling path-way in HIV-1.It is expected to provide new treatment strategies for the clinical treatment of AIDS.

Radiation-induced rectal injury (RRI) refers to inflammatory intestinal complications of patients with pelvic cavity, abdominal cavity and retroperitoneal tumor during or after radiotherapy, presenting symptoms such as diarrhea, abdominal pain, anal distension, bloody stool, etc. In severe cases, rectovaginal fistula, intestinal obstruction, canceration can occur, adversely affecting the quality of life of patients. The clinical factors of RRI involve total radiotherapy dose, tumor volume, radiotherapy mode and patient-related risk factors. The diagnosis mainly depends on imaging examinations (such as CT, MRI and ultrasound), endoscopy and laboratory examination. The mechanism of RRI is related to intestinal epithelial cell destruction, stem cell injury, microvascular changes and microbial flora imbalance. At present, there is no gold standard for RRI treatment, and the main measures include surgical treatment, internal medicine treatment, hyperbaric oxygen therapy and fecal microbiota transplantation, etc. In this article, the latest progress in the pathogenesis, diagnosis and treatment of RRI was reviewed.

Objective　To shorten the detection time of Staphylococcus aureus (SA), this study established a rapid detection method for the thermostable nuclease nuc gene and mecA resistance gene of SA based on recombinase aided amplification (RAA) combined with lateral flow strips (LFS). Methods Efficient RAA primers and probes were designed and screened based on the conserved sequences of the nuc gene in the SA genome and the mecA gene on the staphylococcal SCCmec removable genetic element, and then, the reaction temperature and for the simultaneous detection of nuc and mecA genes by time of RAA-LFS were verified. Sensitivity, specificity, and comparison with quantitative real-time PCR (qPCR) were also assessed. A prospective evaluation was conducted using 52 vials of non-repeat positive blood cultures from two tertiary hospitals. Results The RAA-LFS was able to amplify both nuc and mecA genes under the reaction conditions of 20-45 °C for 15-30 minutes, with a detection limit of 10² CFU/mL. A total of 50 clinically isolated non-SA strains were validated with 100% specificity for both nuc and mecA genes. Of the 30 methicillin-resistant Staphylococcus aureus (MRSA) and 30 methicillin-susceptible Staphylococcus aureus (MSSA) strains preserved in our laboratory, all were positive for the nuc gene, and 30 strains were positive for the mecA gene. The positive and negative concordance rates with qPCR were both 100%, with a consistency test Kappa value of 1. In a prospective analysis of the 52 vials of positive blood cultures, the identification and antibiotic susceptibility test results of 16 strains of MSSA and 6 strains of MRSA showed a 100% concordance rate with the results obtained using the Mérieux VITEK-2 compact microbiological detection system. Conclusions We combined nucleic acid release agents, RAA, and lateral flow strips to develop a simple, rapid, and highly sensitive assay applicable for SA and mecA resistance gene detection in colonies or positive blood culture bottles.

Objective To investigate the clinical features of of patients with Staphylococcus aureus blood-stream infection and risk factors for septic shock.Methods A total of 51 patients diagnosed with Staphylococ-cus aureus bloodstream infection in the hospital from January 2018 to March 2023 were enrolled in the study.According to whether the patients developed septic shock,they were divided into septic shock group and non-septic shock group.The clinical data of the patients were collected,and the clinical laboratory indicators were detected on the day of blood culture samples were collected.Bacteria isolated from blood culture specimens of patients were identified and tested for drug sensitivity.The clinical data and clinical laboratory test indicators of the two groups were compared.Multivariate Logistic regression was used to analyze the independent risk factors of septic shock in patients with Staphylococcus aureus bloodstream infection.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of clinical laboratory test indicators for septic shock in patients with Staphylococcus aureus bloodstream infection.Results Septic shock occurred in 12 of 51 patients,with an incidence of 23.5％.The proportion of patients with diabetes,gouty arthritis,the proportion of patients with long-term glucocorticoid use,the proportion of patients with respiratory tract in-fection,the proportion of patients who died,and the hospitalization cost in the septic shock group were higher than those in the non-septic shock group,and the differences were statistically significant(P＜0.05).Long-term glucocorticoid use was an independent risk factor for septic shock in Staphylococcus aureus bloodstream infection(P＜0.05).The combination of C-reactive protein(CRP),albumin(Alb),neutrophil/lymphocyte ratio(NLR)and procalcitonin(PCT)had high value in predicting septic shock in patients with Staphylococ-cus aureus bloodstream infection,and the area under the ROC curve was 0.983.Conclusion Long-term use of glucocorticoids can lead to an increased risk of septic shock in patients with Staphylococcus aureus blood-stream infection.The combined detection of CRP,Alb,NLR and PCT has a higher predictive value than single detection for septic shock in patients with Staphylococcus aureus bloodstream infection.

Objective:To establish and validate a gallstones classification method based on deep learning.Methods:A total of 618 gallstones samples were collected from East Hospital Affiliated to Tongji University, and 1 023 high-definition cross-sectional gallstones profile images were captured to construct a cross-sectional gallstones profile image dataset. Based on the traditional eight-category gallstones classification method, a lightweight network model, MobileNet V3, was trained using deep learning and transfer learning methods. The classification performance of MobileNet was evaluated using a confusion matrix with metrics such as accuracy rate, precision rate, F1 score, and recall rate. The MobileNet V3 was improved and further validated using accuracy and loss values.Results:The accuracy rate (94.17%), precision rate (94.03%), F1 score (92.96%) and recall rate (92.99%) of the improved MobileNet V3 model were better than other networks. The improved MobileNet V3 model achieved the highest accuracy rate (94.17%) in gallstones profile classification and was validated by the test set. The confusion matrix showed a weighted average of accuracy rate (92.0%), precision rate (92.6%), and F1 score (92.2%) for each category of gallstones.Conclusions:Based on deep learning, a high-accuracy gallstones classification method is proposed, which provides a new idea for the intelligent identification of gallstones.

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.