BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Objective To systematically evaluate the predictive models for re-admission in patients with heart failure (HF) in China. Methods Studies related to the risk prediction model for HF patient re-admission published in The Cochrane Library, PubMed, EMbase, CNKI, and other databases were searched from their inception to April 30, 2024. The prediction model risk of bias assessment tool was used to assess the risk of bias and applicability of the included literature, relevant data were extracted to evaluate the model quality. Results Nineteen studies were included, involving a total of 38 predictive models for HF patient re-admission. Comorbidities such as diabetes, N-terminal pro B-type natriuretic peptide/brain natriuretic peptide, chronic renal insufficiency, left ventricular ejection fraction, New York Heart Association cardiac function classification, and medication adherence were identified as primary predictors. The area under the receiver operating characteristic curve ranged from 0.547 to 0.962. Thirteen studies conducted internal validation, one study conducted external validation, and five studies performed both internal and external validation. Seventeen studies evaluated model calibration, while five studies assessed clinical feasibility. The presentation of the models was primarily in the form of nomograms. All studies had a high overall risk of bias. Conclusion Most predictive models for HF patient re-admission in China demonstrate good discrimination and calibration. However, the overall research quality is suboptimal. There is a need to externally validate and calibrate existing models and develop more stable and clinically applicable predictive models to assess the risk of HF patient re-admission and identify relevant patients for early intervention.

Objective To assess the situation and influencing factors of occupational burnout among the staff at the Center for Disease Control and Prevention (CDC) in Sichuan Province. Methods A total of 1 038 CDC staff members in Sichuan Province were selected as the study subjects using the stratified random sampling method. Occupational burnout of the staff was assessed using the Maslach Burnout Inventory General Survey via an online questionnaire. Results The detection rate of occupational burnout was 42.3% (439/1 038). Binary logistic regression analysis result showed that, after controlling for confounding factors such as education level and alcohol consumption, CDC staffs aged at 20-<31, 31-<41, and 41-<51 years were at higher risk of occupational burnout compared with those ≥51 years (all P<0.05). CDC staffs with 5-<10 or ≥10 years of service had higher occupational burnout risk compared with those with <5 years (both P<0.05). CDC staffs with poor or fair health status, irregular diet, and poor sleep quality had higher risk of occupational burnout compared with those healthy, have regular diet, and good sleep quality (all P<0.05). The risk of occupational burnout increased with higher overtime frequency (all P<0.05). Conclusion Occupational burnout among CDC staffs in Sichuan Province is relatively high. Age, years of service, health status, diet, sleep quality, and overtime frequency are key influencing factors.

Objective To investigate the effects of ganoderma lucidum polysaccharide peptide(GLPP)on renal function and oxidative damage in diabetic nephropathy mice and its mechanism.Methods C57 mice were randomly divided into normal group,model group,positive control group(10.0 mg·kg-1 losartan),experimental-L group(50 mg·kg-1 GLPP),experimental-M group(100 mg·kg-1 GLPP),experimental-H group(200 mg·kg-1 GLPP)and GLPP+Losartan group(200 mg·kg-1 GLPP+10.0 mg·kg-1 losartan).Each group had 10 mice.After 8 weeks of continuous gastric administration,blood glucose was detected;renal function and lipid metabolism related indexes were detected by biochemical analyzer;serum inflammatory factor expression was detected by enzyme linked immunosorbent assay(ELISA);protein expression was detected by Western blot;oxidative damage related indexes were detected by kit method;apoptosis was detected by Tunel method.Results The fasting blood glucose of mice in normal group,model group,positive control group,experimental-H group and GLPP+Losartan group were(4.69±0.16),(20.31±2.04),(10.22±0.98),(10.26±0.96)and(7.76±0.43)mmol·L-1;serum creatinine(Scr)level were(25.48±2.33),(68.34±4.78),(32.93±3.25),(36.37±2.36)and(28.30±1.19)μmol·L-1,respectively;malonaldehyde(MDA)content were(2.05±0.22),(6.71±0.57),(2.69±0.27),(3.21±0.32)and(2.19±0.11)nmol·L-1,respectively;Tunel positive cell rates were(3.39±0.27)％,(26.75±1.24)％,(6.81±0.71)％,(8.05±0.80)％,(5.33±0.33)％,respectively;nuclear factor kappa B(NF-κB p65)protein expression levels were 0.31±0.05,1.07±0.08,0.40±0.03,0.47±0.04 and 0.35±0.03,respectively.The model group compared with the normal group for the above indicators,the experimental-H group compared with the model group for the above indicators,and the GLPP+Losartan group was compared with the experimental-H group for the above indicators,all differences were statistically significant in statistics(all P＜0.05).Conclusion Ganoderma lucidum polysaccharide peptide may regulate Toll-like receptor 4/NF-κB pathway to inhibit apoptosis and inflammatory response,and improve oxidative damage in diabetic nephropathy mice.

Opioid analgesics are currently known as the best analgesics. However， toxicity and side effects such as constipation， tolerance and addiction severely limit their clinical application. With the in-depth understanding of the signal transduction mechanism of opioid receptors and the continuous advancement of drug design technology， researchers have managed to develop many promising new methods to get low-toxic and more efficient opioid analgesics， which are different from the traditional morphine skeleton structure modifications. This article focuses on three new research strategies of G-protein biased activation，“ one drug-multiple targets” and peripheral activation. The basic principles of relative separation of analgesic activity and adverse drug reaction by each strategy are introduced， and the latest research progress of representative drugs is briefly reviewed. Among them， the recently approved novel opioid analgesics oliceridine and tegileridine are G-protein biased μ-opioid receptor agonists， Cebranopadol is a typical “one drug-multiple targets” analgesic， and NFEPP is a representative drug of peripheral opioid receptor agonists. The above several strategies complement each other and provide reference for the development of new opioid analgesic drugs.

Objective:To explore the expression pattern of pyroptosis-related genes(PRGs)in hepatocellular carcinoma(HCC),and analyze the relationship between its expression and tumor prog-nosis and immune microenvironment.Methods:TCGA database was used to analyze the genetic changes and expression patterns of PRGs in primary HCC cells,and cluster analysis was used to i-dentify the pyrogenic subtypes of HCC.To compare the difference of prognosis and immune mi-croenvironment among HCC pyrodeath subtypes.Scorch death score quantified the comprehensive expression of PRGs in each sample,and analyzed the correlation between scorch death score and each immune score.Results:Two pyroptosis-associated subtypes of primary HCC were identi-fied,and the expression pattern of PRGs is closely related to the prognosis of cancer patients and the tumor microenvironment.The subtype with high expression of PRGs had a poor prognosis,and functional enrichment analysis found that some tumor-promoting pathways and PD-1 checkpoint pathways were significantly enriched in this subtype.And various cells and immune checkpoints re-lated to immunosuppression were also enriched in this subtype.By constructing PYROPTO-SIS_score to quantify the comprehensive expression of pyroptosis-related genes in each sample,it was found that PYROPTOSIS_score was significantly positively correlated with tumor-infiltrating macrophages,myeloid-derived suppressor cells,and Treg cells.Conclusion:These results sug-gest that pyroptosis may play a tumor-promoting as well as immunosuppressive role in HCC,pro-viding new insights into the assessment of tumor patient prognosis and the immune microenviron-ment.

Objective To investigate the mutation types of colorectal neuroendocrine tumors(NETs)and better un-derstand the pathogenesis of colorectal nets.Methods Patients undergoing colorectal NETs surgery were recruited,colorectal NETs and corresponding adjacent cancerous tissues were collected,and whole genome sequencing(WGS)was performed and further deeply analyzed.Results WGS sequencing showed that the mutation types of colorectal NETs included single nucleotide mutations,insertion and deletion mutations(InDel,less than 50 bp in length),copy number variations(CNV),and large structural variations(SV,more than 50 bp in length),such as insertion(INS),deletion(DEL),intra chromosomal translocation(ITX),inter chromosomal translocation(CTX)and inversion(INV).Conclusions A large number of somatic mutations occur in colorectal NETs,especially chro-mosome translocation

Objective To investigate the clinical efficacy of transjugular intrahepatic portosystemic shunt(TIPS)combined with indwelling catheter-directed thrombolysis for the treatment of portal vein thrombosis(PVT).Methods The clinical efficacy of 307 patients with portal hypertension complicated by PVT,who received successful TIPS combined with indwelling catheter-directed thrombolysis at the Affiliated Beijing Shijitan Hospital of Capital Medical University of China between January 2016 and December 2019,were retrospectively analyzed.Before and after TIPS,the inferior vena cava pressure(IVCP)and portal vein pressure(PVP)were measured,and the pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis portal pressure gradient(PPG,PPG=PVP-IVCP)was separately calculated.Reexamination of portal venography DSA was performed to determine the degree of PVT disappearance and whether the shunt was unobstructed.All patients were followed up for one year.Results The pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis mean PPG was(24.50±6.91)mmHg,(18.51±5.11)mmHg,and(10.17±3.97)mmHg,respectively.The post-thrombolysis mean PPG was strikingly lower than the pre-thrombolysis values,the differences were statistically significant(P＜0.001).Among the 307 patients,complete disappearance of PVT was observed in 221(72.3%),remarkable reduction of PVT in 86(27.7%),and no invalid result was seen.The patients having complete patency of the shunt flow accounted for 85.7%of the 307 patients(261/307),and the patients having partial patency of the shunt flow accounted for 14.3%of the 307 patients(46/307).Forty-two patients developed complications,and no death occurred.All patients were followed up for one year,and the main clinical symptoms were improved or completely disappeared.Among the 307 patients,an increase in thrombus volume was found in 17(5.5%)when compared to their postoperative values,which returned to the first-time postoperative level after local treatment of the thrombus via the TIPS shunt combined with catheter-directed thrombolysis.Within one year after TIPS and thrombolysis,overt hepatic encephalopathy(OHE)occurred in 54 patients(17.6%,54/307).One patient died of hepatic failure 9 months after TIPS,another patient died of cerebral hemorrhage 11 months after TIPS,and all the remaining patients were alive.Conclusion For patients with portal hypertension complicated by PVT,TIPS combined with indwelling catheter-directed thrombolysis is clinically safe and effective.The standardized,systematic management of the whole therapeutic process should be strengthened.(J Intervent Radiol,2024,32:22-27)

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:Combined retrograde tracing with optogenetic methods,we are investigating the functional role of dorsal raphe nucleus(DRN)GABAergic neurons projecting to lateral habenula(LHb)terminals in anxiety-like behaviors.Methods:The specific retrograde tracing virus AAVretro-Ef1α-DIO-mCherry was injected into the LHb of Vgat-Cre mice.After the viral expression,Multi-brain slides scanning microscope imaging scan and observe the up-stream distribution of GABAergic neural projection in LHb.By retrograde tracing,opto-activated virus AAV2/9-Ef1a-DIO-ChR2-mCherry(ChR2 group)and control virus AAV2/9-Ef1a-DIO-mCherry(mCherry group)were injected into the DRN of Vgat-cre mice respectively.Three weeks after virus expression,DRNGABA neurons and the DRNCABA-LHb neural terminals were activated by optogenetic to observe their role in anxiety-like behaviors.Results:According to the results of retrograde tracing,the midbrain DRN is one of the major GABAergic neural projection brain areas in the LHb nucleus.Optogenetic stimulation of DRNGABA neurons,compared with the mCherry group,the ChR2 group showed sig-nificantly longer total moving distance,central area moving time and distance in the open field test(OFT);In the ele-vated plus maze(EPM),the open arm moving time and distance was significantly increased.When DRN GABA-LHb neural terminals were stimulated,compared with the mCherry group,the ChR2 group showed a significantly longer cen-tral zone moving time,distance and total moving distance in the OFT.During the elevated plus maze(EPM),the open arm moving time was significantly increased.Conclusion:The specific activation of the DRNGABA neuron as well as the DRNGABA-LHb neural projections showed that both significantly improved anxiety-like behaviors in mice.This provides new ideas and evidence for the treatment of anxiety,depression and other psychiatric disorders.