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.

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.

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 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.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

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:Based on the Six Sigma(6σ)management process improvement DMAIC model,to construct the management model of thoracic laparoscopy equipment in operating room,and to analyze its application effect in the management of thoracic laparoscopy in operating room.Methods:Based on the data analysis of the definition,measurement,analysis,improvement and control stages of DMAIC model,the optimization and improvement strategies of thoracic laparoscopic equipment management in operating room were developed.50 sets of thoracic laparoscopic equipment in clinical use in The First Affiliated Hospital of Xi'an Jiaotong University from 2021 to 2022 were selected,and traditional management mode and DMAIC management model were adopted respectively.A self-made questionnaire was used to investigate the satisfaction with the use of the equipment and the mastery of equipment-related knowledge of the two management modes among the maintenance and use personnel of thoracic and laparoscopic equipment,and the incidence of equipment failure in the two management modes was compared.Results:The incidence of adverse events of thoracic laparoscopic equipment in operating room using the DMAIC model management mode was 2.00%(1/50),which was lower than that of traditional management mode,the difference was statistically significant(x2=8.155,P<0.05).The satisfaction of the of maintenance personnel with the use thoracic laparoscopic equipment adopting DMAIC model management mode was 100.00%(50/50),which was higher than that of traditional management mode,the difference was statistically significant(x2=8.696,P<0.05).The average scores of medical staff's basic equipment use knowledge,equipment cleaning and disinfection knowledge and equipment routine maintenance knowledge of thoracic laparoscopic equipment using DMAIC model management mode were(96.28±4.82)points,(94.69±4.73)points and(96.26±4.16)points,respectively,which were higher than those of the traditional management mode,the difference was statistically significant(t=6.023,9.746,12.619,P<0.05).Conclusion:The application of the management mode of thoracic laparoscopy equipment in operating room based on DMAIC model to the management of thoracic laparoscopy equipment in hospital operating room can reduce the incidence of adverse conditions during the use of thoracic laparoscopy equipment,improve the satisfaction of equipment users,and improve the understanding and mastery of equipment related knowledge of medical staff.

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 mechanism of electroacupuncture in relieving the apoptosis of retinal cells in experimental myopia based on mitochondrial dynamics.Methods In the study,140 two-week-old tricolor guinea pigs were divided into the normal control(NC)group,lens-induced myopia(LIM)group,LIM+sham acupoint(LIM+SHAM)group,and LIM+electroacupuncture intervention(LIM+EA)group,with 35 guinea pigs in each group.Guinea pigs in the NC group were fed normally,and those in the LIM group,LIM+SHAM group and LIM+EA group wore a-6.0D lens on the right eye to induce myopia.Guinea pigs in the LIM+EA group were treated at Hegu and Taiyang acupoints,while those in the LIM+SHAM group were treated at sham acupoints.After 2-and 4-week myopia induction,the diopter and axial length of the guinea pigs were measured,and the messenger ribonucleic acid(mRNA)and protein levels of dynam in-related pro-tein 1(DRP1),optic atrophy 1(OPA1),Bcl-2 associated X protein(BAX)and B cell lymphoma-2(BCL-2)in the retinas of the guinea pigs in each group were detected by quantitative PCR and Western blot,respectively.Meanwhile,HE staining was taken to observe the morphological changes in the retina of the guinea pigs in each group,and TUNEL staining was used to detect apoptosis.Results After 2-and 4-week myopic induction,compared with the NC group,the differences in diopter and axial length between the right and left eyes of guinea pigs in the LIM and the LIM+SHAM groups significantly increased(all P＜0.001).Compared with the LIM group,the differences in diopter and axial length between both eyes of guinea pigs in the LIM+EA group significantly decreased(all P＜0.01).At 4 weeks after myopic induction,HE staining re-sults showed that the retinas of the guinea pigs in the NC group were evenly arranged,and the morphology of inner and out-er nuclear layer cells was normal.Compared with the NC group,the retinas of the guinea pigs in the LIM and the LIM+SHAM groups were significantly thinner and disorderly arranged.Compared with the LIM group,the retinal thickness of guinea pigs in the LIM+EA group slightly increased,and the arrangement was relatively regular.The TUNEL staining re-sults showed that compared with the NC group,the green fluorescence of the guinea pig retina in the LIM group and LIM+SHAM group was significantly enhanced;compared with the LIM group,the green fluorescence of the guinea pig retina in the LIM+EA group was significantly weaken.After 2-and 4-week myopic induction,the mRNA and protein expression lev-els of DRP1 and BAX in the LIM and the LIM+SHAM groups were significantly higher than those in the NC group(all P＜0.05),while the mRNA and protein expression levels of OPA1 and BCL-2 were significantly lower(all P＜0.05).The mR-NA and protein expression levels of DRP1 and BAX in the LIM+EA group were significantly lower than those in the LIM group(all P＜0.05),while the mRNA and protein expression levels of OPA1 and BCL-2 were significantly higher(all P＜0.05).Conclusion Experimental myopia can enhance retinal mitochondrial fission.Electroacupuncture intervention can alleviate retinal cell apoptosis and improve the morphological structure of the retina by inhibiting retinal mitochondrial fis-sion and increasing mitochondrial fusion,thereby delaying myopia development.

OBJECTIVE To optimize the heart-nourishing granule extraction process by network pharmacology and Box-Behnken response surface method. METHODS The active ingredients of heart-nourishing granule were excavated through network pharmacology and their mechanism of action in the treatment of coronary heart disease was preliminarily explored. Molecular docking technology was used to predict the binding ability of the active ingredients to the main targets. At the same time, based on the compatibility relationship between the monarch, minister, assistant and guide of the prescription, the pharmacological effects of the ingredients, and the content determination index components of each medicinal flavor in the 2020 edition of the Chinese Pharmacopoeia, the process evaluation index components of heart-nourishing granule were further determined. In addition, combined with the analytic hierarchy process to determine the weight of each component, the Box-Behnken response surface method was used to optimize the extraction process of heart-nourishing granule. RESULTS The main active components of heart-nourishing granule screened were catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin. By acting on core targets such as AKT1, IL-6, IL-1b, VEGFA, JUN and MAPK3, they regulated lipid and atherosclerosis, MAPK signaling and other pathways played a role in the treatment of coronary heart disease. Molecular docking results showed that the binding energies of active components and core targets predicted by network pharmacology were all < -5.0 kJ·mol-1. Five components catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin were calculated by analytic hierarchy process method. The weight coefficients of arginyl glycosides were 0.329 7, 0.329 7, 0.164 8, 0.109 9, and 0.065 9, respectively. The Box-Behnken response surface method obtained the optimal water extraction process: 10 times the amount of water was used to extract twice, and each time was decocted for 1.5 h. The verification test showed that the contents of the five components were consistent with the predicted values, and the RSD values were all <5%. CONCLUSION The extraction process of heart-nourishing granule based on network pharmacology and Box-Behnken response surface methodology is stable and feasible, which provided an experimental basis for its further quality improvement.