Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

Objective:To determine incidence of seasonal influenza virus infection in the community and to analyze the factors influencing seasonal influenza virus infection.Methods:This study recruited residents aged 6-59 years to build a cohort in 15 villages/streets in Macheng city in November 2019. Meanwhile, a cross-sectional baseline survey was conducted immediately to collect sera, information on demographics and child protection knowledge, behaviors, as well as attitudes using a questionnaire from the participants enrolled in the cohort (i.e., before the influenza epidemic season). In July 2020, a cross-sectional follow-up survey was conducted to collect sera once again (i.e., after the influenza season). Paired sera from the two cross-sectional surveys were tested for influenza virus-specific antibodies by hemagglutination inhibition (HI) test or micro-neutralization (MN) test using a circulating representative strain of each subtype/lineage of influenza virus as the test antigen. The infections with influenza virus subtype/lineage was confirmed if there was a four-fold or more increase in titers of antibodies against circulating representative strain of the subtype/lineage of influenza virus. Factors influencing infection with influenza A (H3N2) and B/Victoria viruses were analyzed using univariable and multivariable logistic regression.Results:In November 2019, 800 study participants were enrolled in the cohort, including 340 children aged 6-17 years and 460 adults aged 18-59 years; 605 study participants (including 224 children and 381 adults) were followed up in July 2020 and their paired sera were obtained before and after the influenza season. 25.3% (153/605) of the participants were confirmed to be infected with at least one subtype/lineage of seasonal influenza virus by HI and MN tests. The overall incidence of influenza viruses of all subtypes/lineages in children was 44.2% (95% CI: 37.6%-50.8%) which was significantly higher than the incidence of 14.1% in adults (95% CI: 10.7%-17.7%). Children had the highest incidence of influenza A (H3N2) virus infection, followed by B/Victoria. MN or HI antibody titers in A (H3N2)[ OR=0.88 (95% CI: 0.84-0.93)] and B/Victoria[ OR=0.97 (95% CI: 0.95-0.99)] before the influenza season were significantly associated with whether children were infected with that subtype/lineage of influenza virus. Conclusions:The residents aged 6-59 years in Macheng city had a substantial incidence of seasonal influenza virus infection during the influenza season from winter 2019 to spring 2020. Notably, almost half of children aged 6-17 years have been infected with seasonal influenza virus. Higher titers of HI/MN antibodies against seasonal influenza virus before the influenza season would be likely to reduce the risk of infection with influenza A (H3N2) and B/Victoria.

Objective To investigate the effect of preoperative dexmedetomidine(DEX)combined with fascia iliac compartment block(FICB)analgesia on perioperative sleep quality and delirium in elderly patients with hip fracture.Methods A total of 90 elderly patients who received total hip replacement(THA)for hip fracture in our hospital from January 2021 to June 2023 were selectively included,and all patients were randomly divided into control group(n=30),FICB group(n=30)and combination group(n=30).Patients in control group were prepared according to routine surgical procedures before surgery.Patients in combination group and FICB group were given continuous ultrasus-guided iliofascial space block and analgesia two days before surgery after admission.Patients in combination group were given dexmedetomidine nose drops on the night before surgery,the day after surgery and the night after surgery.Visual analogue pain(VAS)scores were recorded at admission(Tl),30 minutes after nasal drops(T2),immediately after entry to the operating table(T3),and at the position of intraspinal anesthesia(T4).Hamilton Anxiety(HAM-A)score and Athens Insomnia Scale(AIS)score were recorded 1 day before surgery,1 day after surgery and 1 day after surgery.Adverse reactions and postoperative delirium(POD)were recorded one week after surgery.Results There were no significant differences in age,sex,body mass index(BMI),fracture type,anesthesia duration,operation time,blood loss and adverse reactions(except daytime sleepiness)among all groups(P＞0.05).The VAS scores of T2,T3 and T4 in the combination group were significantly lower than those in the other two groups.HAM-A and AIS scores were significantly lower than those of the other two groups(P＜0.05).The incidence and duration of postoperative delirium were significantly lower than those in the other two groups(P＜0.05).Conclusion Prospective randomized controlled trials show that FICB combined with DEX can relieve pain,improve perioperative sleep quality and relieve postoperative delirium in patients with THA.

Objective To investigate the value of CT radiomics combined with CT and preoperative pathological features for predicting postoperative early recurrence(ER)of local advanced esophageal squamous cell carcinoma(LAESCC).Methods Data of 334 patients with LAESCC were retrospectively analyzed.The patients were divided into training set(n=234)and verification set(n=100)at the ratio of 7:3 and were followed up to observe ER(recurrence within 12 months after surgery)or not.Univariate and multivariate logistic regression were used to analyze clinical,CT and preoperative pathological features of LAESCC in patients with or without ER in training set.The independent risk factors of ER were screened,and a CT-preoperative pathology model was constructed.Based on venous phase CT in training set,the radiomics features of lesions were extracted and screened to establish radiomics model,and finally a combined model was established based on radiomics model and the independent risk factors.Receiver operating characteristic(ROC)curves were drawn,and the area under the curve(AUC)was calculated to evaluate the diagnostic efficacy of each model.Results Among 334 cases,168 were found with but 166 without ER.In training set,117 cases were found with while the rest 117 without ER,while in verification set,51 were found with but 49 without ER.The length of lesions,cT stage and cN stage shown on CT and tumor differentiation degree displayed with preoperative pathology were all independent risk factors for ER of LAESCC(all P＜0.05).The AUC of CT-preoperative pathology model in training set and validation set was 0.759 and 0.783,respectively.Ten best radiomics features of LAESCC were selected,and AUC of the established radiomics model in training set and validation set was 0.770 and 0.730,respectively.The AUC of combined model in training and validation set was 0.838 and 0.826,respectively.The AUC of CT radiomics combined with CT and preoperative pathological features in training set was higher than that of CT-preoperative pathologymodel and radiomics model(both P＜0.01).Conclusion CT radiomics combined with CT and preoperative pathological features could effectively predict postoperative ER of LAESCC.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To summarize the endoscopic and clinical diagnosis and treatment of 4 cases of gastric fundus adenocarcinoma.Method A retrospective analysis was conducted on the clinical data of four cases of gastric fundus adenocarcinoma from July 2021 to December 2023.Result All the 4 cases of gastric fundus adenocarcinoma were completely removed by endoscopic submucosal dissection(ESD),with good postoperative recovery,no surgical complications,and no recurrence or metastasis during follow-up.Conclusion ESD treatment for gastric fundus adenocarcinoma is safe,reliable,and can completely remove the lesion.

Objective To optimize the conditions and improve the efficiency for the differentiation of pluripotent stem cells(PSCs)into cerebral organoids.Methods Based on the induction differentiation system for inducing hu-man embryonic stem cells(hESCs)H9 towards cerebral organoids,a combination of small molecule compounds was added to the developmental stage of neural progenitor cells in the early stage of cerebral organoid differentia-tion,and the efficiency of neural progenitor cell formation,apoptosis and differentiation into neurons in cerebral or-ganoids in the differentiation stage were observed through morphology,the expression of marker genes was detected by RT-qPCR and the effect of small molecule compound combination on cerebral organoids was comprehensively evaluated.Results At the critical stage of neural progenitor cell development(1 d-14 d)of cerebral organoids,dorsomorphine,A83-01,GSK-3β inhibitor CHIR99021 and SMAD inhibitor SB-431542 were successively added to the medium.It could significantly increase the expression of marker genes in the neural progenitor cell stage,promote the formation of specific neural tube-like structures and reduce apoptosis in the central region of cerebral organoids.Conclusions By using the combination of four small molecule compounds,the formation efficiency in early cerebral organoids can be significantly improved,apoptosis in cerebral organoids can be reduced,neuronal formation can be promoted,and tissue structure heterogeneity in the culture process can be reduced.

BACKGROUND:Osteonecrosis of the femoral head is a common orthopedic disease,and hip preservation surgery with bone grafting is commonly used in the early stage,in which autologous bone and allograft bone are commonly used as bone grafting materials.However,autologous bone transplantation is highly traumatic and bone supply is limited,and allograft bone is rich in sources,but there are serious risks of immune rejection and absorption.In recent years,the tissue engineering technique based on mesenchymal stem cells is a new method for the treatment of femoral head necrosis,which is gradually widely used after basic experiments and clinical application. OBJECTIVE:To review the application and prospect of tissue engineering in the treatment of osteonecrosis of the femoral head to provide a new choice for the clinical treatment of osteonecrosis of the femoral head. METHODS:The PubMed database and CNKI database from 2013 to 2023 were searched by the first author with Chinese and English search terms"tissue engineering,mesenchymal stem cells,biological scaffolds,cytokines,osteonecrosis of the femoral head,bone graft,hip preservation".The articles on the treatment of osteonecrosis of the femoral head with tissue engineering technology were selected,and 55 representative articles were included for review after the initial screening of all articles according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)With the continuous development of biotechnology and materials science,great progress has been made in the treatment of osteonecrosis of the femoral head by bone tissue engineering,such as the application of gene-modified mesenchymal stem cells to repair osteonecrosis,the combination of gene recombination technology and surface modification technology with bone tissue engineering in the treatment of osteonecrosis of the femoral head.(2)When applied to the necrotic femoral head,tissue engineering technology can promote the regeneration of necrotic bone tissue and the repair of the vascular system,provide biomechanical stability for the necrotic area,and use bioactive factors to accelerate the repair of seed cells to complete the regeneration of new bone in necrotic area.(3)However,most of these studies are still in the animal experiment stage,and there are still many unsolved problems and challenges in bone tissue engineering research.With the rapid development of nanotechnology,tissue engineering and clinical medicine,biomimetic replacement bone grafting materials with perfect performance are expected to come into being.(4)In the future,bone tissue engineering for osteonecrosis of the femoral head is expected to be a satisfactory treatment for patients with hip preservation.

OBJECTIVE:Percutaneous sacroiliac screw internal fixation has become the main surgical procedure for the treatment of posterior pelvic ring fractures;however,the unassisted closure operation requires high operator experience and repeated fluoroscopy increases the radiation hazard for patients and medical personnel.This article compares the clinical efficacy of robot-assisted versus unassisted percutaneous sacroiliac screw placement for posterior pelvic ring fractures by meta-analysis. METHODS:Computer searches of CNKI,WanFang,VIP,CBM,PubMed,Embase,Cochrane Library and ClinicalTrials.gov were conducted from the time of database inception to December 2022.The literature on the clinical efficacy of robot-assisted versus freehand percutaneous sacroiliac screw placement in the treatment of posterior pelvic ring fractures was collected in and outside China.The data were independently screened and extracted by two investigators according to the inclusion and exclusion criteria,respectively.The quality of randomized controlled trials was evaluated using Cochrane risk assessment criteria.The quality of included cohort studies was assessed using the Newcastle-Ottawa Scale.Meta-analysis was performed using RevMan 5.4 software for inclusion metrics.Outcome metrics included operative time,intraoperative bleeding,fluoroscopy time,fluoroscopy frequency,number of holes drilled,Majeed postoperative function score,the excellent and good rates of Matta fracture reduction,the excellent and good rates of Gras screw position,fracture healing time and complications. RESULTS:(1)A total of 13 publications were included,2 were randomized controlled trials both referring to randomized methods,11 non-randomized controlled studies were evaluated for quality of literature according to the Newcastle-Ottawa Scale,1 scored 8,9 scored 7;and 1 scored 6;the quality of literature was good.A total of 748 patients were included,including 430 in the robot-assisted group and 318 in the freehand group.(2)The results of the meta-analysis showed that the operative time(MD=-28.30,95%CI:-40.20 to-16.40),intraoperative bleeding(MD=-6.36,95%CI:-10.06 to-2.66),intraoperative fluoroscopy time(MD=-12.13,95%CI:-19.54 to-4.72),intraoperative fluoroscopy frequency(MD=-17.39,95%CI:-29.00 to-5.78),number of intraoperative needle drillings(SMD=-9.50,95%CI:-14.27 to-4.73)and the excellent and good rates of Gras screw position(OR=8.65,95%Cl:3.26-22.92)in the robot-assisted group were significantly better than those in the freehand group(P<0.05).(3)In the robot-assisted group,the overall postoperative complication rate was significantly reduced(OR=0.10,95%Cl:0.02-0.48,P<0.05).(4)No significant difference was detected in fracture healing time(MD=-0.08,95%CI:-0.21,0.06),the excellent and good rates of Matta fracture repositioning rate(OR=2.06,95%Cl:0.97-4.39),and Majeed functional score(MD=0.91,95%CI:-0.31-2.13)between both groups(P>0.05). CONCLUSION:Compared with freehand sacroiliac joint nailing,robotic assistance shortens the operative time,reduces intraoperative bleeding,decreases radiation damage to patients and medical staff,improves the excellent and good rate of screw position,and reduces the overall incidence of postoperative complications in patients,but there was no significant improvement in fracture reduction quality,fracture healing time,and postoperative function.In the future,more large-sample,multicenter,and high-quality randomized controlled trials are still needed to verify.