Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To investigate the distribution and clinical significance of amniotic fluid karyotype results in 2 725 cases from southern Anhui.Methods:The karyotypes of amniotic fluid from 2 725 cases of second-trimester pregnant women treated in our hospital from Jan 2017 to Dec 2023 were collected.The annual abnormal detection rate and overall abnormal rate were analyzed.Meanwhile,the abnormal detection rate was compared among 8 groups of different clinical indication including adverse pregnancy history,advanced maternal age(≥35 years),high risk of Down syndrome screening,high risk of non-invasive prenatal testing(NIPT),nuchal translucency thickness(NT)≥2.5 mm,abnormal ultrasound findings,two or more concurrent positive indications,and others.The abnormal detection rate was calculated within high risk of Down syndrome screening and NIPT.Results:Significant differences in annual abnormal rates were observed from 2017 to 2023(χ2=19.705,P=0.003).Among 2 725 cases,233(8.55%)showed abnormal karyotypes.Among them,abnormal autosomal number was the most prevalent(4.41%,120/2 725),with inversion being the most common chromosome structural abnormality.Significant differences in abnormal rates were noted among the eight clinical indication groups(χ2=438.516,P＜0.01).No statistical difference was found in abnormal detection rates among the three high-risk subgroups of Down syndrome screening(χ2=0.323,P=0.851),while significant differences were observed within the high-risk subgroups of NIPT(χ2=100.901,P＜0.01).Polymorphisms were detected in 65 cases(2.38%).Conclusions:Chromosomal numerical and structural abnormalities have been detected in southern Anhui over the past seven years,with variations across subgroups.Karyotype analysis effectively detects second-trimester fetal chromosomal abnormalities,aiding in the prevention of birth defects and worthing clinical application.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

ObjectiveTo investigate the effect of the nitroglycerin-controlled low central venous pressure （CLCVP） technique on brain metabolic markers and cerebral blood oxygen saturation in patients undergoing laparoscopic hepatectomy for liver cancer， and to reduce the risk of neurological complications. MethodsA total of 105 patients who underwent elective laparoscopic hepatectomy for liver cancer in Haikou Hospital Affiliated to Xiangya Hospital of Central South University from April 2020 to May 2023 were enrolled and randomly divided into CLCVP group with 54 patients and non-CLCVP group with 51 patients. The patients in the CLCVP group were treated with the nitroglycerin CLCVP technique during surgery， while those in the non-CLCVP group were given conventional surgical treatment. The two groups were compared in terms of the following indicators： perioperative indicators； hemodynamic parameters and cerebral oxygen metabolism before anesthesia induction （T0）， at 5 minutes after anesthesia induction （T1）， at 5 minutes after the beginning of liver parenchyma dissection （T2）， at 5 minutes after the end of hepatectomy （T3）， and immediately after the end of surgery （T4）； the changes in liver function parameters after surgery； the incidence rate of adverse reactions. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the analysis of variance with repeated measures was used for comparison between multiple time points. ResultsCompared with the non-CLCVP group， the CLCVP group had significantly lower intraoperative blood loss and intraoperative fluid infusion volume （t=5.408 and 7.220， both P<0.05）， while there were no significant differences between the two groups in time of operation， anesthesia time， extubation time， resuscitation time and intraoperative urine volume （all P>0.05）. Compared with the data at T0， both groups had significant reductions in mean arterial pressure， heart rate， and central venous pressure during surgery （all P<0.05）， and compared with the non-CLCVP group， the CLCVP group had significantly lower mean arterial pressure and central venous pressure （P<0.05） and a significantly higher heart rate （P<0.05） at T2 and T3. Compared with the data at T0， both groups had a significant reduction in Ca-jvDO₂ at T2‍ ‍—‍ ‍T4 time points （all P<0.05）， while there was no significant difference in Ca-jvDO₂ between the two groups at each time point （all P>0.05）. Compared with the data at T0， the CLCVP group had a significant reduction in rSO₂ at T2‍ ‍—‍ ‍T4 time points （all P<0.05）， and the CLCVP group had a significantly lower level of rSO₂ than the non-CLCVP group at T2‍ ‍—‍ ‍T3 time points （both P<0.05）； there were no significant changes in CERO₂ and Djv-aBL in either group at each time point （all P>0.05）. At 3 and 7 days after surgery， both groups had significant increases in the liver function parameters of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， and total bilirubin （TBil） （all P<0.05）， and the CLCVP group had significantly lower levels of AST and ALT than the non-CLCVP group （all P<0.05）； there was no significant difference in TBil between the two groups at each time point （all P>0.05）. There was no significant difference in the incidence rate of perioperative complications between the two groups （χ²=0.729， P=0.394）. ConclusionThe application of the nitroglycerin CLCVP technique in laparoscopic hepatectomy for liver cancer can reduce the amount of intraoperative blood loss in patients， but it is necessary to further enhance the monitoring of cerebral blood oxygen saturation during surgery， so as to reduce the risk of neurological complications as much as possible.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To extract and evaluate the relevant evidence to improve the family discharge preparation of premature infants with bronchopulmonary dysplasia, so as to provide evidence-based basis for clinical formulation of scientific and effective discharge plans.Methods:All the evidence on the family discharge readiness of premature infants with bronchopulmonary dysplasia was collected from Chinese and English databases or websites, and the quality of various studies was evaluated. JBI′s evidence grading and recommendation level system (2014 edition) was used to extract and summarize the evidence.Results:A total of 21 articles were included, and 24 pieces of evidence were summarized, which were divided into seven themes: pre-discharge planning, environmental preparedness, parent education and training, support systems, feeding and nutrition, respiratory management, and discharge follow-up.Conclusions:For preterm infants with bronchopulmonary dysplasia, discharge readiness should be improved in terms of standardizing discharge criteria and implementing a discharge plan; improving family care preparation to ensure discharge support; strengthening health management and implementing a personalized plan; and continuing high-quality follow-up to ensure long-term health.

Objective:To extract and evaluate the relevant evidence to improve the family discharge preparation of premature infants with bronchopulmonary dysplasia, so as to provide evidence-based basis for clinical formulation of scientific and effective discharge plans.Methods:All the evidence on the family discharge readiness of premature infants with bronchopulmonary dysplasia was collected from Chinese and English databases or websites, and the quality of various studies was evaluated. JBI′s evidence grading and recommendation level system (2014 edition) was used to extract and summarize the evidence.Results:A total of 21 articles were included, and 24 pieces of evidence were summarized, which were divided into seven themes: pre-discharge planning, environmental preparedness, parent education and training, support systems, feeding and nutrition, respiratory management, and discharge follow-up.Conclusions:For preterm infants with bronchopulmonary dysplasia, discharge readiness should be improved in terms of standardizing discharge criteria and implementing a discharge plan; improving family care preparation to ensure discharge support; strengthening health management and implementing a personalized plan; and continuing high-quality follow-up to ensure long-term health.

Objective:To investigate the distribution and clinical significance of amniotic fluid karyotype results in 2 725 cases from southern Anhui.Methods:The karyotypes of amniotic fluid from 2 725 cases of second-trimester pregnant women treated in our hospital from Jan 2017 to Dec 2023 were collected.The annual abnormal detection rate and overall abnormal rate were analyzed.Meanwhile,the abnormal detection rate was compared among 8 groups of different clinical indication including adverse pregnancy history,advanced maternal age(≥35 years),high risk of Down syndrome screening,high risk of non-invasive prenatal testing(NIPT),nuchal translucency thickness(NT)≥2.5 mm,abnormal ultrasound findings,two or more concurrent positive indications,and others.The abnormal detection rate was calculated within high risk of Down syndrome screening and NIPT.Results:Significant differences in annual abnormal rates were observed from 2017 to 2023(χ2=19.705,P=0.003).Among 2 725 cases,233(8.55%)showed abnormal karyotypes.Among them,abnormal autosomal number was the most prevalent(4.41%,120/2 725),with inversion being the most common chromosome structural abnormality.Significant differences in abnormal rates were noted among the eight clinical indication groups(χ2=438.516,P＜0.01).No statistical difference was found in abnormal detection rates among the three high-risk subgroups of Down syndrome screening(χ2=0.323,P=0.851),while significant differences were observed within the high-risk subgroups of NIPT(χ2=100.901,P＜0.01).Polymorphisms were detected in 65 cases(2.38%).Conclusions:Chromosomal numerical and structural abnormalities have been detected in southern Anhui over the past seven years,with variations across subgroups.Karyotype analysis effectively detects second-trimester fetal chromosomal abnormalities,aiding in the prevention of birth defects and worthing clinical application.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.