The plasma membrane (PM) plays an essential role in maintaining cell homeostasis, therefore, timely and effective repair of damage caused by factors such as mechanical rupture, pore-forming toxins, or pore-forming proteins is crucial for cell survival. PM damage induces membrane rupture and stimulates an immune response. However, damage resulting from regulated cell death processes, including pyroptosis, ferroptosis, and necroptosis, cannot be repaired by simple sealing mechanisms and thus, requires specialized repair machinery. Recent research has identified a PM repair mechanism of regulated cell death-related injury, mediated by the endosomal sorting complexes required for transport (ESCRT) machinery. Here, we review recent progress in elucidating the ESCRT machinery-mediated repair mechanism of PM injury, with particular focus on processes related to regulated cell death. This overview, along with continued research in this field, may provide novel insights into therapeutic targets for diseases associated with dysregulation of regulated cell death pathways.

BackgroundAs a high prevalence disorder， schizophrenia has caused significant burden to family and society due to the impairment of occupational and social function. Currently， the dominant vocational training model in China follows a paternalistic， clinician-led decision-making approach. Although it improves patients' social function to some extent， it undermines their autonomy and treatment adherence. Therefore， it is urgently necessary to explore a new intervention method to enhance treatment compliance and social function in patients. ObjectiveTo explore the impact of shared decision-making oriented vocational training on social function in hospitalized schizophrenia patients， so as to provide references for rehabilitation interventions. MethodsA total of 68 patients diagnosed with schizophrenia according to the International Classification of Diseases， tenth edition （ICD-10） criteria were consecutively enrolled from January to June 2024 at The Third People's Hospital of Wenjiang Distric， Chengdu. Participants were randomly allocated into the research group （n=34） and the control group （n=34） using a random number table method. Both groups received routine rehabilitation training， while the research group received shared decision-making oriented vocational training for 12 weeks， 2 times a week for 2 hours each time. Before and at the 4^th and 12^th week of intervention， two groups were evaluated by General Self-Efficacy Scale （GSES）， Stigma Scale for Mental Illness （SSMI）， Scale of Social function of Psychosis Inpatients （SSFPI） and Inpatient Psychiatric Rehabilitation Outcome Scale （IPROS）. ResultsA total of 63 participants completed the study， with 30 cases in the research group and 33 cases in the control group. Repeated measures ANOVA revealed statistically significant time effects and interaction effects in both groups for GSES， SSMI， SSFPI and IPROS scores （F=20.451， 16.022； 26.193， 12.944； 23.957， 5.023； 11.776， 3.985， P<0.05 or 0.01）， while no significant group effects were observed （F=0.188， 0.742， 1.878， 0.474， P>0.05）. At the 12^th week of intervention， there were statistically significant differences in GSES， SSMI， SSFPI and IPROS scores between the two groups. ConclusionShared decision-making oriented vocational training may help to improve social function in patients with schizophrenia. ［Funded by 2023 Chengdu Medical Research Project （number， 2023468）］

OBJECTIVE: To investigate the efficacy and safety of the conditioning regimen BeEAM (bendamustine+et-oposide+cytarabine+melphalan) in autologous stem cell transplantation (ASCT) for patients with malignant lymphoma. METHODS: The clinical data of 20 patients with malignant lymphoma who underwent ASCT after conditioning with BeEAM regimen from January 2021 to December 2022 in the First Affiliated Hospital of Bengbu Medical University were collected, and the clinical characteristics before transplantation, conditioning-related toxicity, hematopoietic reconstitution after transplantation, and therapeutic effects were analyzed. 67 patients with malignant lymphoma who did not undergo ASCT during the same period were selected as the control group, and the 1-year progression-free survival (PFS) rate and overall-survival (OS) rate between the ASCT group and the non-ASCT group were compared. RESULTS: 15 cases achieved complete remission (CR) and 5 cases achieved partial remission (PR) before transplantation in ASCT group. During the conditioning process of patients in the ASCT group, 14 cases experienced gastrointestinal adverse reactions, 13 cases experienced neutropenic fever, 10 cases experienced oral mucositis, 2 cases experienced abnormal liver function, and only 1 case experienced acute renal injury. All the adverse reactions resolved after symptomatic treatment. After transplantation, 19 cases achieved hematopoietic reconstitution, and only one case had poor platelet engraftment. The median time of peripheral white blood cell (WBC) engraftment was 9 (9-16) days, and the median time of platelet engraftment was 12 (10-23) days. By the end of follow-up, there were no transplant-related deaths. The 1-year PFS rates in the ASCT group and the non-ASCT group were 94.4% and 68.5%, respectively; The 1-year OS rates were 94.4% and 83.5%, respectively. The median PFS and OS time for both groups were not reached. The PFS in the ASCT group was significantly better than that in the non-ASCT group (P < 0.05), and there was no significant difference in OS between the two groups ( P >0.05). CONCLUSION BeEAM regimen is safe and effective as a conditioning treatment for ASCT in patients with malignant lymphoma, with tolerable adverse reactions, controllable non-hematological toxicity, smooth hematopoietic reconstitution, and considerable short-term efficacy. However, further follow-up is required to evaluate its long-term efficacy.
Humans ; Transplantation Conditioning/methods* ; Transplantation, Autologous ; Hematopoietic Stem Cell Transplantation ; Lymphoma/therapy* ; Cytarabine/therapeutic use* ; Female ; Male ; Melphalan/therapeutic use* ; Adult ; Middle Aged ; Bendamustine Hydrochloride/therapeutic use*

Objective To investigate the effect of NOD-like receptor family pyrin domain containing 3(NLRP3)knockdown on a mouse model of nonalcoholic steatohepatitis(NASH)induced by high-fat high-carbohydrate(HFHC)diet.Methods A total of 44 mice were randomly divided into normal diet group(CON group)with 20 mice and HFHC group with 24 mice.At the end of week 14 of modeling,4 mice were randomly selected from the HFHC group for the pre-experiment of adeno-associated virus(AAV)by tail vein injection,and NLRP3 knockdown was verified after 4 weeks.After NLRP3 knockdown was verified at the end of week 18,the remaining 40 mice were given a single tail vein injection of AAV,and then they were divided into CON+NLRP3 knockdown negative control group(CON+NLRP3-NC group),CON+NLRP3 knockdown group(CON+NLRP3-KD group),HFHC+NLRP3-NC group,and HFHC+NLRP3-KD group,with 10 mice in each group.At the end of week 24,the activation of NLRP3 inflammasome was observed;related indicators were measured,including body weight,liver weight,liver index,and glucose metabolism(fasting blood glucose,fasting insulin,and Homeostasis Model Assessment of Insulin Resistance[HOMA-IR]index);the indicators of liver lipid content(liver triglyceride[TG]and oil red O staining),liver inflammation(serum alanine aminotransferase[ALT]activity,HE staining,and inflammation-related genes),and liver fibrosis(Sirius Red staining and fibrosis-related genes)were measured.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the CON+NLRP3-NC group based on the results of Western Blot,the HFHC+NLRP3-NC group had significant increases in the protein expression levels of NLRP3,pro-Caspase1,Caspase1,ASC,and IL-1β,while the HFHC+NLRP3-KD group had significant reductions in these levels(all P<0.05).The HFHC+NLRP3-NC group showed varying degrees of increase in body weight,liver weight,liver index,and glucose metabolism indicators,while the HFHC+NLRP3-KD group showed significant improvements in these indicators(all P<0.05).As for hepatic fat deposition,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had a significant increase in liver TG,with a large number of red lipid droplets shown by oil red O staining,and the HFHC+NLRP3-KD group had significant reductions in liver TG and the number of lipid droplets in the liver(all P<0.01).In terms of liver inflammation,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had significant increases in serum ALT,NAFLD activity score,and inflammation-related genes,while the HFHC+NLRP3-KD group had significant reductions in these indicators(all P<0.01).As for liver fibrosis,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had significant increases in collagen fiber area and fibrosis-related genes,and the HFHC+NLRP3-KD group had significant reductions in fibrosis-related genes(all P<0.05)and a tendency of reduction in collagen fiber area(P>0.05).Conclusion NLRP3 knockdown can significantly improve hepatic fat deposition and inflammation in a mouse model of HFHC-induced NASH.

Linezolid,a fully synthetic oxazolidinone antibiotic,is mainly used to treat severe infections caused by Gram-positive drug-resistant bacteria.In recent years,with the rise in drug-resistant bacteria,the clinical utilization rate of linezolid and the incidence of linezolid-related adverse reactions in the hematological system and metabolic system have increased.The main adverse reactions include thrombocytopenia,anemia and lactic acidosis.Studies have shown that the causes of adverse reactions in linezolid-induced hematological system and metabolic system are diverse,and the mechanisms are not fully elucidated.In this review,the pharmacokinetic characteristics,mechanism of adverse reactions,risk factors,as well as preventive measures and individualized drug administration strategies of linezolid in vivo were discussed based on literature reports at home and abroad,aiming to provide references for clinical prevention and treatment of linezolid-related adverse reactions of hematological system and metabolic system.

Objective:To investigate the risk factors for sepsis in patients severe trauma.Methods:A retrospective case-control study was conducted to analyze the clinical data of 149 patients with severe trauma admitted to General Hospital of Ningxia Medical University from January 2021 to June 2022, including 112 males and 37 females, aged 18-93 years [(50.6±16.3)years]. According to whether the patients developed sepsis, they were divided into sepsis group ( n=66) and non-sepsis group ( n=83). A comparison was made between the two groups in gender, age, measurements of body temperature, heart rate, respiration, systolic blood pressure, diastolic blood pressure, mean artery pressure (MAP), oxygen saturation (SPO 2), white blood cell (WBC), absolute neutrophil count (ANC), percentage of neutrophils (NEUT%), red blood cell count (RBC), hemoglobin (HGB), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer level, level of lactic acid, level of blood glucose, quick sequential organ failure assessment (qSOFA), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II) score, Glasgow coma scale (GCS), and injury severity score (ISS) within 24 hours of admission, causes of injury, injury sites, number of injury sites, hemorrhagic shock (HS), open injury, endotracheal intubation, length of ICU stay and total length of hospital stay. Univariate analysis and multivariate Logistic regression analysis were used to determine the independent risk factors for severe post-traumatic sepsis. Results:The results of univariate analysis showed that there were statistically significant differences in age, respiration, SPO 2, WBC and ANC, D-dimer level, blood glucose level, qSOFA, SOFA, APACHE II score, GCS, ISS, head and neck injury, open injury, tracheal intubation, length of ICU stay, and total length of hospital stay between the sepsis group and non-sepsis group ( P<0.05 or 0.01); whereas there were no significant differences in gender, underlying disease, body temperature, heart rate, systolic blood pressure, diastolic blood pressure, MAP, NEUT%, RBC, HGB, PLT, PT, APTT, lactic acid level, cause of injury, facial injury, chest injury, abdominal and pelvic injury, limb and pelvic injury, number of injury sites, and HS between the two groups ( P>0.05). Multivariate Logistic regression analysis showed that D-dimer level ( OR=0.97, 95% CI 0.96, 0.99, P<0.01) and tracheal intubation ( OR=15.80, 95% CI 2.14, 116.69, P<0.01) were significantly correlated with sepsis in patients with severe trauma. Conclusion:D-dimer level collected within 24 hours of admission and tracheal intubation are independent risk factors for sepsis in patients with severe trauma.

Objective:To investigate the correlation between nutritional status and quality of life in inpatients with nasopharyngeal carcinoma and to analyze the factors affecting nutritional status,so as to provide evidence for clinical nutritional support treatment.Methods:In this study,we retrospectively collected data from patients with nasopharyngeal carcinoma who met the inclusion and exclusion criteria in the Head and Neck Oncology Department of Zunyi Medical University Affiliated Hospital from 2014 to 2019.The NRS 2002 scale was used for nutritional risk screening,the PG-SGA scale for nutritional status assessment and the EORTCQLQ-C30 V3.0 scale for quality of life assessment.To further explore the correlation between nutritional status and quality of life,as well as the factors affecting nutritional status.Results:A total of 216 patients were collected,including 168 male(77.78%);average age(50.5±10.58)years;26.85%were at nutritional risk(NRS 2002 score≥3);28.70%were moderate malnutrition(PG-SGA score 4-8),and 23.15%were severe malnutrition(PG-SGA score≥9).There were significant differences in several physical examinations(such as body weight,body mass index,muscle circumference at the midpoint of the upper arm,etc.)and blood biochemical indexes(such as prealbumin,neutrophils,urea nitrogen,etc.)of patients with different nutritional status were differed between groups(P<0.05).Univariate analysis showed that age≥65 years was a risk factor for the development of severe malnutrition(OR:3.429,95%CI:1.467 to 8.014,P=0.004),whereas a high level of education(senior high school and above)was a protective factor(OR:0.027,95%CI:0.011 to 0.064,P=0.000).The poorer the nutritional status of nasopharyngeal carcinoma patients,the lower the quality of life.Conclusion:Nasopharyngeal carcinoma patients have a high incidence of malnutrition;the poorer the nutritional status of the patient,the lower the quality of life;routine nutritional diagnosis and treatment of nasopharyngeal carcinoma patients after admission to the hospital is recommended to improve clinical outcomes.

Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12α-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase(CYP7A1)and sterol-12α-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-α hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential ther-apeutic targets for obesity-related disorders.

Objective To establish a method for HPLC fingerprint analysis and determine three main components of Modified Zengye Decoction.Methods The chromatographic column was Shimadzu WondaSil C18 column(250 mm×4.6 mm,5 μm),the mobile phase was acetonitrile-0.3％aqueous phosphoric acid with a gradient elution procedure,the volume flow rate was 1.0 mL/min,the detection wavelengths were 265,203,310 and 290 nm,the column temperature was 25 ℃,and the injection volume was 20 μL.The HPLC fingerprints of the 10 batches of Modified Zengye Decoction were established,and the similarity analysis was performed by using the similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine(version 2012A).The common peaks were identified and assigned,and the contents of the three main components were quantitatively determined.Results There were 17 common peaks in the fingerprints of 10 batches of Modified Zengye Decoction with similarities ranging from 0.872-0.989.The fingerprints recognized peak 9,14 and 17 as ferulic acid,aurantiamarin and harpagoside,respectively.The contents of ferulic acid,aurantiamarin and harpagoside were 0.067 3-0.174 8,0.498 8-1.522 7,0.270 9-0.802 4 mg/g,and the transfer rate were 30.74％-55.63％,11.77％-35.94％,23.15％-68.56％,respectively.Conclusion The established HPLC fingerprint analysis method combined with main components quantitative analysis method can be used for the quality analysis and control of Modified Zengye Decoction with simple analysis method and reliable results.

Unilateral biportal endoscopic surgery, micro-endoscopic discectomy, micro-endoscopic laminoplasty, and Destandau mobile endoscopic discectomy have been described as four major techniques in the field of endoscopic spine surgeries. Compared with the coaxial endoscopy, the unilateral biportal endoscopic surgery is characterized by separated channels for observation and operation, making operative procedures more flexible, vision field wider, and requirements for surgical instruments less demanding. Although the anatomical basis of its surgical approach is similar to that of micro-endoscopic spine surgery, this technique can significantly reduce the injury to the paravertebral muscle and protect the stability of the surgical segment of the spine, leading to quick and wide applications in the clinical treatment of degenerative lumbar diseases with good clinical efficacy. The present article reviews this surgical technique from the aspects of technological development, anatomical basis, clinical application, complications, and prospects.