Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

OBJECTIVE: To explore the effectiveness and feasibility of two osteotomy guides in medial open wedge high tibial osteotomy (MOWHTO). METHODS: Clinical data of 103 patients who underwent routine MOWHTO surgery between January 2020 and December 2022 were collected for retrospective analysis. The patients were divided into two groups based on the method of osteotomy guide plate. The control group of 51 patients received traditional osteotomy guide plate technique, including 17 males and 34 females, aged from 48 to 68 years old with an average of(57.93±4.82) years old, with a disease duration ranged from 1 to 8 years with an average of (4.89±1.49) years. The observation group of 52 patients received personalized osteotomy guide plate technique, including 23 males and 29 females, aged from 48 to 69 with an average of (58.22±5.10) years, with a disease duration ranged from 1 to 9 years with an average of(5.10±1.55) years. The perioperative indicators, complications, and knee joint recovery rate were statistically analyzed for both groups, as well as the preoperative and postoperative coagulation function, fibrinogen (FIB), D-dimer (D-D), gait parameters (step frequency, step length, step speed), biomechanical indicators, weight bearing line (WBL), medial proximal tibial angle (MPTA), joint line conergence angle (JLCA), and anterior cruciate ligament (ACL) function (body width, tibial anterior displacement). RESULTS: All patients were followed up for 6 months. The intraoperative blood loss, operation time, and number of fluoroscopic views in the observation group were (358.58±93.76) ml, (84.42±8.17) min, and (2.00±0.44) times, respectively, which were all less than those in the control group (465.55±105.38) ml, (96.53±10.51) min, and (6.31±0.58) times (P<0.05). Three days after surgery, the FIB and D-D levels in the observation group were (4.21±0.48) g·L^-1 and (204.47±35.59) μg·L^-1, respectively, which were both lower than those in the control group (5.56±0.57) g·L^-1 and (311.12±42.23) μg·L^-1 (P<0.05). Three months after surgery, the step frequency, step length, and step speed in the observation group were (1.89±0.23) steps·s^-1, (0.57±0.15) m, and (0.99±0.11) m·s^-1, respectively, which were all higher than those in the control group (1.80±0.18) steps·s^-1, (0.50±0.14) m, and (0.95±0.09) m·s^-1 (P<0.05). Three months after surgery, the WBL and MPTA in the observation group were (45.53±4.41)% and (87.03±8.15)°, respectively, which were both higher than those in the control group (38.38±4.36)% and (83.68±8.50)°, and the JLCA was (2.36±0.24)°, which was lower than that in the control group (2.61±0.33)° (P<0.05). The ACL body width during internal fixation removal was (5.60±0.51) mm, which was greater than that in the control group (5.08±0.56) mm, and the tibial migration was (5.70±0.42) mm, which was less than that in the control group (6.33±0.48) mm (P<0.05). There was no significant difference in the incidence of complications between the two groups (P>0.05). Six months after surgery, there was no significant difference in the recovery rate of knee joint between the two groups (P>0.05). CONCLUSION The application of personalized osteotomy guide technique in MOWHTO can help improve knee biomechanics and ACL function, and has less effect on coagulation function and no increase in complications.
Humans ; Male ; Female ; Osteotomy/methods* ; Middle Aged ; Tibia/physiopathology* ; Aged ; Biomechanical Phenomena ; Retrospective Studies ; Osteoarthritis, Knee/physiopathology*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

As the population is aging rapidly,the incidence of Alzheimer's disease(AD)is increasing year by year.The World Health Organization stresses that early prevention plays a key role in reducing the incidence of AD.Subjective cognitive decline(SCD)is an early window of AD development,and timely intervention can effectively slow down the progression of the disease or prevent it from developing into dementia,thus reducing the burden on the society.White matter hyperintensity(WMH)can effectively reflect white matter changes and provide strong evidence to identify SCD.In this paper,we review the recent research progress in WMH and SCD,reveal the problems in the current research on WMH,explain the correlation between WMH and SCD in terms of physiopathology and cognitive function,and put forward several suggestions for the future research.
Humans ; White Matter/pathology* ; Cognitive Dysfunction/pathology* ; Alzheimer Disease/pathology* ; Magnetic Resonance Imaging

Objective To understand the change in distribution and antimicrobial resistance of bacteria isolated from blood specimens of Hunan Province,and provide for the initial diagnosis and treatment of clinical bloodstream infection(BSI).Methods Data reported from member units of Hunan Province Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacterial antimicrobial resistance surveillance method was imple-mented according to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS).Bacteria from blood specimens and bacterial antimicrobial susceptibility testing results were analyzed by WHONET 5.6 soft-ware and SPSS 27.0 software.Results A total of 207 054 bacterial strains were isolated from blood specimens from member units in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021,including 107 135(51.7％)Gram-positive bacteria and 99 919(48.3％)Gram-negative bacteria.There was no change in the top 6 pathogenic bacteria from 2012 to 2021,with Escherichia coli(n=51 537,24.9％)ranking first,followed by Staphylococcus epidermidis(n=29 115,14.1％),Staphylococcus aureus(n=17 402,8.4％),Klebsiella pneu-moniae(17 325,8.4％),Pseudomonas aeruginosa(n=4 010,1.9％)and Acinetobacter baumannii(n=3 598,1.7％).The detection rate of methicillin-resistant Staphylococcus aureus(MRSA)decreased from 30.3％in 2015 to 20.7％in 2021,while the detection rate of methicillin-resistant coagulase-negative Staphylococcus(MRCNS)showed an upward trend year by year(57.9％-66.8％).No Staphylococcus was found to be resistant to vancomy-cin,linezolid,and teicoplanin.Among Gram-negative bacteria,constituent ratios of Escherichia coli and Klebsiella pneumoniae were 43.9％-53.9％and 14.2％-19.5％,respectively,both showing an upward trend(both P＜0.001).Constituent ratios of Pseudomonas aeruginosa and Acinetobacter baumannii were 3.6％-5.1％and 3.0％-4.5％,respectively,both showing a downward trend year by year(both P＜0.001).From 2012 to 2021,resistance rates of Escherichia coli to imipenem and ertapenem were 1.0％-2.0％and 0.6％-1.1％,respectively;presenting a downward trend(P＜0.001).The resistant rates of Klebsiella pneumoniae to meropenem and ertapenem were 7.4％-13.7％and 4.8％-6.4％,respectively,presenting a downward trend(both P＜0.001).The resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem antibiotics were 7.1％-15.6％and 34.7％-45.7％,respectively.The trend of resistance to carbapenem antibiotics was relatively stable,but has de-creased compared with 2012-2016.The resistance rates of Escherichia coli to the third-generation cephalosporins from 2012 to 2021 were 41.0％-65.4％,showing a downward trend year by year.Conclusion The constituent ra-tio of Gram-negative bacillus from blood specimens in Hunan Province has been increasing year by year,while the detection rate of carbapenem-resistant Gram-negative bacillus remained relatively stable in the past 5 years,and the detection rate of coagulase-negative Staphylococcus has shown a downward trend.

Objective To investigate changes in the distribution and antimicrobial resistance of bacteria isolated from cerebrospinal fluid(CSF)specimens in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021 were collected according to China Antimicrobial Resistance Surveillance Sys-tem(CARSS)technical scheme.Data of bacteria isolated from CSF specimens and antimicrobial susceptibility tes-ting results were analyzed with WHONET 5.6 and SPSS 20.0 software.Results A total of 11 837 bacterial strains were isolated from CSF specimens from member units of Hunan Province Antimicrobial Resistance Surveillance Sys-tem from 2012 to 2021.The top 5 strains were coagulase-negative Staphylococcus(n=6 397,54.0％),Acineto-bacter baumannii(n=764,6.5％),Staphylococcus aureus(n=606,5.1％),Enterococcus faecium(n=465,3.9％),and Escherichia coli(n=447,3.8％).The detection rates of methicillin-resistant coagulase-negative Staphyloco-ccus(MRCNS)and methicillin-resistant Staphylococcus aureus(MRSA)were 58.9％-66.3％and 34.4％-62.1％,respectively.No Staphylococcus spp.were found to be resistant to vancomycin,linezolid,and teicoplanin.The de-tection rate of Enterococcus faecium was higher than that of Enterococcus faecalis,and the resistance rates of En-terococcus f aecium to penicillin,ampicillin,high concentration streptomycin and levofloxacin were all higher than those of Enterococcus faecalis(all P=0.001).Resistance rate of Streptococcus pneumoniae to penicillin was 85.0％,at a high level.Resistance rate of Escherichia coli to ceftriaxone was＞60％,while resistance rates to enzyme inhibitors and carbapenem antibiotics were low.Resistance rate of Klebsiella pneumoniae to ceftriaxone was＞60％,to en-zyme inhibitors piperacillin/tazobactam and cefoperazone/sulbactam was＞30％,to carbapenem imipenem and me-ropenem was about 30％.Resistance rates of Acinetobacter baumannii to most tested antimicrobial agents were＞60％,to imipenem and meropenem were 59.0％-79.4％,to polymyxin B was low.Conclusion Among the bac-teria isolated from CSF specimens,coagulase-negative Staphylococcus accounts for the largest proportion,and the overall resistance of pathogenic bacteria is relatively serious.Bacterial antimicrobial resistance surveillance is very important for the effective treatment of central nerve system infection.

Objective To investigate the distribution and antimicrobial susceptibility of clinically isolated bacteria from intensive care units(ICUs)in hospitals of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods According to China Antimicrobial Resistance Surveillance System,data of clinically isolated bacterial strains and antimicrobial susceptibility testing results of bacteria from ICUs reported by all member units of Hunan Province Antimicrobial Resistance Surveillance System were analyzed with WHONET 2022 software.Results From 2012 to 2021,the total number of bacteria isolated from ICUs of member units of the Hunan Province Antimi-crobial Resistance Surveillance System was 5 777-22 369,with Gram-negative bacteria accounting for 76.1％-78.0％annually.Staphylococcus aureus ranked first among isolated Gram-positive bacteria each year.The top 5 bacteria among Gram-negative bacteria were Acinetobacter baumannii,Klebsiella pneumoniae,Escherichia coli,Pseudo-monas aeruginosa,and Stenotrophomonas maltophilia.Detection rate of methicillin-resistant Staphylococcus aureus showed a downward trend year by year.No Staphylococcus spp.were found to be resistant to vancomycin,teico-planin and linezolid.Detection rates of vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Entero-coccus faecium were 0.6-1.1％and 0.6％-2.2％,respectively.Resistance rates of Escherichia coli and Kleb-siella pneumoniae to imipenem were 3.1％-5.7％and 7.7％-20.9％,respectively.Resistance rates of Pseudo-monasaeruginosa and Acinetobacter baumannii to imipenem were 24.6％-40.1％and 76.1％-80.9％,respective-ly.Detection rates of carbapenem-resistant Pseudomonas aeruginosa declined year by year.Acinetobacter baumannii maintained high susceptibility to polymyxin B,with resistance rate＜10％.Conclusion Antimicrobial resistance of bacteria from ICUs is serious.Carbapenem-resistant Enterobacteriales has an upward trend after 2019.It is nece-ssary to strengthen the surveillance of bacterial resistance and carry out multidisciplinary collaboration.

Objective To understand the antimicrobial resistance of clinically isolated Enterococcus spp.in Hunan Province.Methods Surveillance data of Enterococcus spp.resistance from member units of Hunan Provincial Anti-microbial Resistance Surveillance System from 2012 to 2021 were collected.Data were cleaned according to a unified method,and WHONET 5.6 software was adopted for statistical analysis.Results From 2012 to 2021,a total of 110 652 non-repetitive Enterococcus spp.strains were included in the analysis,mainly Enterococcus faecalis and Enterococcus faecium,accounting for 46.9％(n=37 774)and 45.9％(n=36 968),respectively,followed by En-terococcus avium(2.5％,n=1 982),Enterococcus gallinarum(1.8％,n=1 428),and Enterococcus casseliflavus(1.5％,n=1 185).The main specimen sources of Enterococcus spp.was urine(51.8％,n=57 350),followed by secretions(9.6％,n=10 660)and bile(8.5％,n=9 377).From 2012 to 2021,the resistance rates of Enteroco-ccus faecalis to ampicillin,teicoplanin,and vancomycin were 5.5％-12.0％,1.3％-2.0％,and 0.6％-1.4％,respectively.The resistance rates of Enterococcus faecium to ampicillin,teicoplanin,and vancomycin were 69.2％-85.0％,1.5％-2.8％,and 0.7％-2.5％,respectively.Except for linezolid and minocycline,the resistance rates of Enterococcus faecium to tested antimicrobial agents were all higher than those of Enterococcus faecalis.The re-sistance rates of Enterococcus faecalis and Enterococcus faecium to vancomycin decreased from 1.4％and 2.1％in 2012 to 0.6％and 0.7％in 2021,respectively,presenting a decreased trend.Conclusion Clinically isolated En-terococcus spp.maintain high antimicrobial susceptibility to vancomycin and teicoplanin.Resistance rates of Entero-coccus faecalis and Enterococcus faecium to vancomycin present decreased trends.