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.

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.

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.

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.

ObjectiveTo investigate the role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis. MethodsA total of 18 specific pathogen-free female C57BL/6 mice were selected and divided into normal group， model group， and treatment group using a random number table， with 6 mice in each group. The mice in the model group and the treatment group were injected with concanavalin A （Con A） via the caudal vein to establish a mouse model of autoimmune hepatitis， and those in the normal group were injected with normal saline. The mice in the treatment group were given prophylactic treatment with Yinchenhao Decoction （4.68 g crude drug/kg） by gavage at 14 days before modeling， and Con A was injected after the last gavage. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interferon gamma （IFN-γ）， tumor necrosis factor-α （TNF-α）， iron ion， glutathione （GSH）， reactive oxygen species （ROS）， adenosine triphosphate （ATP）， and malondialdehyde （MDA） were measured； liver index and spleen index were calculated； the expression levels of GPX4 and SLC7A11 were measured； liver histopathological changes were compared between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant reductions in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. Compared with the model group， the treatment group had significant reductions in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant increases in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. HE staining showed that compared with the normal group， the model group showed massive hepatocyte degeneration and necrosis and inflammatory cell aggregation at the portal area， and compared with the model group， the treatment group had alleviation of liver necrosis and inflammatory infiltration. ConclusionLiver injury induced by Con A may be associated with ferroptosis. Yinchenhao Decoction can increase the protein expression levels of SLC7A11 and GPX4 protein and thus inhibit ferroptosis of hepatocytes induced by Con A.

Objective To evaluate the accuracy of three-dimensional(3D)reconstruction of the gallbladder volume based on computed tomography(CT)images and study the biomechanical changes in gallbladder motility to explore the relationship between gallbladder dynamics and gallstone formation.Methods A method for calculating gallbladder volume based on CT 3D reconstruction of The gallbladder model was proposed and compared with the ellipsoid method.A finite element model of the gallbladder was constructed for fluid dynamics analysis to simulate changes in gallbladder motor function under different angles of convergence between the cystic and common bile ducts and in the presence of gallstones.Results The mean errors of the specific gallbladder model volume and ellipsoid volume of the 50 patients were 7.26％and 25.35％,respectively.During the refilling period,the maximum pressure,deformation,and flow velocity of the pear-shaped gallbladder were significantly higher than those of the gourd-shaped gallbladder.The angle between the gallbladder and common bile duct had little effect on the bile flow pattern,and the maximum bile flow rate was reached at an angle of 120°.The bile flow velocity of the gallbladder with calculus was lower than that of the gallbladder without calculus,and there was a vortex near the calculus.Conclusions Calculating gallbladder volume based on CT 3D reconstruction is more accurate than the ellipsoid method.Compared with a pear-shaped gallbladder,a gourd-shaped gallbladder has lower gallbladder wall contraction,bile flow rate,and poor motor function.The bile flow rate in the gallbladder is slow,which is more likely to lead to the enlargement of gallstones or the formation of new gallstones.

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.