Metabolic dysfunction-associated fatty liver disease （MAFLD） progresses to metabolic dysfunction-associated steatohepatitis （MASH） due to mitochondrial homeostasis imbalance and dysfunction in hepatocytes caused by various factors such as lipotoxicity and inflammatory infiltration. Recent studies have confirmed that mitochondrial injury is closely associated with chronic inflammation， with extracellular vesicle （EV） acting as a key mediator linking the two processes. This article systematically reviews the molecular mechanisms of hepatocyte mitochondrial dysfunction in MAFLD/MASH， highlights the regulatory role of hepatocyte-derived EV in intrahepatic inflammation， and discusses the potential application prospects of mitochondria-targeted therapies and intercellular communication interventions in MAFLD/MASH， in order to provide a theoretical basis for developing novel therapeutic strategies for these diseases.

Structural optimization of lead compounds is a crucial step in drug discovery. One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules, thereby accelerating the molecular optimization process. Deep molecular diffusion generative models simulate a gradual process that creates novel, chemically feasible molecules from noise. However, the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules, leading to challenges in modifying the scaffold-based molecular structures, and creates limitations in the stability and diversity of the generated molecules. To address these challenges, we propose a deep molecular diffusion generative model, the three-dimensional (3D) equivariant diffusion-driven molecular generation (3D-EDiffMG) model. The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder (dual-SWLEE) is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions. Additionally, a gate multilayer perceptron (gMLP) block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies. The experimental results show that 3D-EDiffMG effectively generates unique, novel, stable, and diverse drug-like molecules, highlighting its potential for lead optimization and accelerating drug discovery.

Structural optimization of lead compounds is a crucial step in drug discovery.One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption,distribution,metabolism,excretion,and toxicity(ADMET)properties.One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules,thereby accelerating the molecular optimization process.Deep molecular diffusion generative models simulate a gradual process that creates novel,chemically feasible molecules from noise.However,the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules,leading to challenges in modifying the scaffold-based molecular structures,and creates limitations in the stability and diversity of the generated molecules.To address these challenges,we propose a deep molecular diffusion generative model,the three-dimensional(3D)equivariant diffusion-driven molecular generation(3D-EDiffMG)model.The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder(dual-SWLEE)is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions.Addi-tionally,a gate multilayer perceptron(gMLP)block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies.The experimental results show that 3D-EDiffMG effectively generates unique,novel,stable,and diverse drug-like molecules,highlighting its potential for lead optimization and accelerating drug discovery.

Objective To explore the surgical techniques and experiences in the treatment of Peyronie's disease using electric rotary grinding of tunica albuginea plaques followed by graft repair with tunica vaginalis or bovine pericardium under a microscope.Methods A retrospective cohort study was performed on 21 patients with severe penile curvature due to Peyronie's disease admitted in our department from January 2021 and May 2023.All of them underwent microscopic electric rotary grinding of tunica albuginea plaques followed by graft repair surgery.Short-term and mid-term outcomes were observed.Results For the 21 enrolled patients,12(57.1％)underwent repair using unilateral tunica vaginalis,3(14.3％)underwent repair using bilateral tunica vaginalis,and 6(28.6％)underwent repair using bovine pericardium.The operation time was 170～385(average 272±69)min,and the average postoperative follow-up duration was3～24(average 12.1±7.2)months.Seventeen patients(81.0％)had their penis fully extended,while 4 patients(19.0％)had slight dorsal curvature,which was less than 10°.All patients were satisfied with the shape of their penis during erection.The change in penile length was+(1.1±0.5)cm,and 9 patients(42.9％)reported early postoperative penile head numbness,which spontaneously resolved after an average duration of 3.2±1.9 months.All patients were able to successfully engage in sexual activity,with an average penile erection hardness score of 3.8.The overall satisfaction rate was 90.5％post operatively.Conclusion Meticulous dissection of Buck's fascia under a microscope is advantageous in reliably preserving dorsal neurovascular structures.Application of an electric grinding drill for plaque ablation allows for more precise release of the tunica.Graft repair of tunica albuginea defects with testicular tunica vaginalis or bovine pericardium for Peyronie's disease yields overall favorable clinical outcomes and obtains high satisfaction.It is worthy of promotion in clinical practice.

Objective:To explore the distribution of pathogenic bacteria during perioperative period of kidney transplantation(KT)patients and examine drug resistance of major clinical pathogens to commonly used antibiotics to provide references for empirical medication of pathogenic bacteria infection after KT.Methods:From January 1, 2020 to June 30, 2021, 251 patients undergoing deceased donation KT on kidney transplant ward were selected.Clinical samples were collected and distribution and drug resistance of pathogenic bacteria examined for analyzing the incidence of possible donor-derived infections and predicting prognoses.Results:The detection rate of pathogens was 12.18%(367/3 014). A total of 225 non-repetitive strains were isolated.Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 48.89%(110/225), 43.11%(97/225)and 8.00%(18/225). The proportion of lavage fluid in all isolated bacteria was 49.78%(112/225). And Staphylococcus epidermidis and Klebsiella pneumoniae predominated.Drainage fluid accounted for 24.88%(56/225)and Pseudomonas putida and Staphylococcus haemolyticus predominated.Urine accounted for 18.67%(42/225)with a dominance of Enterococcus faecium; blood accounted for 6.22%(14/225)with a dominance of S. epidermidis.All detected pathogens showed varying degrees of resistance.The resistance rates of E. faecium to ampicillin, vancomycin and linezolid were 93.33%(28/30), 6.45%(2/31)and 38.71%(12/31). The resistance rates of K. pneumoniae and Acinetobacter baumannii to carbapenems were 71.43%(20/28)and 80.00%(12/15). The incidence of possible donor-derived infection was 3.59%(9/251)and there was no mortality.Conclusions:The detection rate of pathogenic bacteria is high in KT patients during perioperative period.There is a diverse distribution of isolates of different specimen types and all detected pathogens show varying degrees of drug resistance.Clinicians should regularly analyze the distribution characteristics and causes of drug-resistant bacteria.And antibiotics should be optimized according to the results of drug sensitivity.

OBJECTIVE：To evaluate the efficacy and safety of atomization inhalation of polymyxin combined in the adjunctive treatment for ventilator-associated pneumonia ，and to provide evidence-based reference for clinical treatment. METHODS ： Retrieved from Cochrane Library ，Embase，PubMed，Web of Science ，CNKI，CBM，VIP and Wanfang database （from their inception to March 2021），randomized controlled trials （RCTs）about efficacy and safety of atomization inhalation of polymyxin combined with conventional treatment （trial group ） versus conventional treatment （control group ） for ventilator- associated pneumonia were collected. After data extraction and quality evaluation of included literatures met inclusion and exclusion criteria ， Meta-analysis was performed by using Rev Man 5.4 software. RESULTS ：A total of 13 clinical studies were included ，involving 2 RCTs and 11 cohort studies with a total of 1 066 patients. The results of Meta-analysis showed that clinical response rate [OR ＝ 1.53，95％CI（1.17，2.00），P＝0.002]，microbial clearance rate [OR ＝1.46，95％CI（1.11，1.91），P＝0.007] of trial group were significantly higher than those of control group ，with statistical significance. There was no statistical significance in the mortality rate [OR ＝0.88，95％CI（0.68，1.14），P＝0.32] and the incidence of renal impairment [OR ＝1.04，95％CI（0.72，1.49），P＝0.85] between 2 groups. CONCLUSIONS ：Based on current evidence ，atomization inhalation of polymyxin combined with conventional treatment can significantly improve clinical response rate and microbial clearance rate of patients with ventilator- associated pneumonia. However ， more strictly-designed ， long-term follow-up and large-scale RCTs are needed.

Purpose To investigate the application value in diagnosis of pleural effusion by cell block combined with immunohisto-chemistry. Methods 60 cases of pleural effusion were collected, and paraffin-embedded cell block was prepared and immunohisto-chemistry was used to detect the expression of CK7, TTF-1, E-cadherin, CEA and Calretinin. Results By use of cell block combined with immunohistochemistry, malignant detected rate was higher than that of the conventional centrifugal smear. There was statistical significance in the expression of CK7, TTF-1, E-cadherin, CEA and Calretinin between pleural effusion lung adenocarcinoma and reac-tive hyperplasia mesothelial cells (P<0. 05). CK7, TTF-1, E-cadherin and CEA were highly expressed in pleural effusion of lung ad-enocarcinoma cell. Calretinin was highly expressed in hyperplastic mesothelial cells. Conclusion Cell block and immunohistochemi-cal technique combination in the differential diagnosis of difficult pleural effusion has important clinical significance. It is worthy of popularization and further clinical application.

Objective To analyze solitary fibrous tumor (solitary fibrous tumor, SFT) ’s clinical manifestations, patholog-ical features, immunohistochemical phenotype, and follow-up, discuss the diagnosis, differential diagnosis and progno-sis. Methods Ten cases of SFT were analyzed by clinical data and follow-pathological characteristics study and im-munohistochemical staining of Vimentin, CD34, Bcl-2, CD99, SMA and β-catenin. Results There were 6 males and 4 females with ranging in age from 31 to 78 years (mean 53.2 years old). SFT in four cases originated from the visceral pleura, two cases from parietal pleura,one from the skin of the chest wall, one from the neck, one from the medi-astinum, one from subcutaneously. Microscopic examination of tumor tissue was mainly composed of spindle cells, dif-ferent levels of visible cells and cell-rich areas of sparse areas, tumor cells were short spindle or oval, mitotic due to the severity varies. During the visible rich collagen fibers, may be associated with hyaline degeneration or myxoid change. Immunohistochemistry revealed the tumor cells expessed Vimentin, CD34, Bcl-2, CD99 and β-catenin, SMA focal or weakly positive. Conclusion SFT may occur in various sites of the body. The clinicopathological features and immunohistochemical profile are helpful to identify SFT. Its biological behavior is consistent with its histological mor-phology and growth the way. If tumor could be removed completely, the patients may have a good prognosis;some have low-grade malignant or malignant behaviour, manifesting as local recurrence or metastasis. Patients need long-term follow-up.