Objective To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g-1;the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL-1;the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g-1;the relative expression levels of HIF-1 α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P＜0.05,P＜0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

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 explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g-1;the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL-1;the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g-1;the relative expression levels of HIF-1 α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P＜0.05,P＜0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

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.

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.

Objective To investigate the effect of Farrerol on the myocardial injury induced by doxorubicin(Dox)in rats with dilated cardiomyopathy(DCM).Methods SD rats were given intraperitoneal injection of 2.5 mg·kg-1 Dox to establish the DCM model.The rats were randomly divided into normal group(given the same amount of 0.9％NaCl by gavage),model group(establish the DCM model),experimental-L group(given 12.5 mg·kg-1·d-1 farrerol by gavage),experimental-H group(given 50 mg·kg-1·d-1 farrerol by by gavage),combine group(given 50 mg·kg-1·d-1 farrerol+1.5 mg·kg-1·d-1 C26 by gavage).Cardiac function was detected after drug intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of 11,12-EET and 14,15-EET,the products of epoxyeicosatrienoic acids(EETs)in myocardial tissue.Western blot was used to detect the protein expression of cytochrome P450 cyclooxygenase 2J2(CYP2J2)in myocardial tissue.Results The left ventricular end diastolic diameter(LVEDD)of normal group,model group,experimental-L,-H groups and combine group were(5.44±0.15),(6.23±0.36),(6.14±0.58),(5.66±0.22)and(6.16±0.35)mm;the left ventricular ejection fraction(LVEF)were(83.36±2.05)％,(59.66±5.93)％,(56.63±3.20)％,(74.67±3.33)％and(61.95±5.38)％;the creatine kinase(CK)levels were(346.10±49.51),(874.50±85.52),(860.30±46.38),(371.20±50.83)and(789.44±86.48)U·L-1;the apoptosis rates of cardiomyocytes were(2.34±0.91)％,(20.11±3.85)％,(18.94±1.65)％,(10.64±1.23)％and(17.56±2.02)％;the11,12-EET levels were(28.79±4.21),(9.69±3.43),(10.71±3.89),(21.85±5.46)and(12.94±4.60)pg·mg-1;the 14,15-EET levels were(33.12±3.47),(12.75±4.34),(13.27±7.20),(25.18±6.21)and(16.25±2.08)pg·mg-1;the CYP2J2 protein expression levels were 1.20±0.08,0.19±0.04,0.19±0.05,0.85±0.05 and 0.33±0.05,respectively.The differences of above indicators were statistically significant between the model group and the normal group,between the experimental-H group and the model group,as well as between the combine group and the experimental-H group(all P＜0.01).Conclusion Farrerol can improve Dox-induced myocardial injury in DCM rats,and its mechanism may be related to the activation of the CYP2J2/EETs pathway.

Objective To investigate the effect of Farrerol on the myocardial injury induced by doxorubicin(Dox)in rats with dilated cardiomyopathy(DCM).Methods SD rats were given intraperitoneal injection of 2.5 mg·kg-1 Dox to establish the DCM model.The rats were randomly divided into normal group(given the same amount of 0.9％NaCl by gavage),model group(establish the DCM model),experimental-L group(given 12.5 mg·kg-1·d-1 farrerol by gavage),experimental-H group(given 50 mg·kg-1·d-1 farrerol by by gavage),combine group(given 50 mg·kg-1·d-1 farrerol+1.5 mg·kg-1·d-1 C26 by gavage).Cardiac function was detected after drug intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of 11,12-EET and 14,15-EET,the products of epoxyeicosatrienoic acids(EETs)in myocardial tissue.Western blot was used to detect the protein expression of cytochrome P450 cyclooxygenase 2J2(CYP2J2)in myocardial tissue.Results The left ventricular end diastolic diameter(LVEDD)of normal group,model group,experimental-L,-H groups and combine group were(5.44±0.15),(6.23±0.36),(6.14±0.58),(5.66±0.22)and(6.16±0.35)mm;the left ventricular ejection fraction(LVEF)were(83.36±2.05)％,(59.66±5.93)％,(56.63±3.20)％,(74.67±3.33)％and(61.95±5.38)％;the creatine kinase(CK)levels were(346.10±49.51),(874.50±85.52),(860.30±46.38),(371.20±50.83)and(789.44±86.48)U·L-1;the apoptosis rates of cardiomyocytes were(2.34±0.91)％,(20.11±3.85)％,(18.94±1.65)％,(10.64±1.23)％and(17.56±2.02)％;the11,12-EET levels were(28.79±4.21),(9.69±3.43),(10.71±3.89),(21.85±5.46)and(12.94±4.60)pg·mg-1;the 14,15-EET levels were(33.12±3.47),(12.75±4.34),(13.27±7.20),(25.18±6.21)and(16.25±2.08)pg·mg-1;the CYP2J2 protein expression levels were 1.20±0.08,0.19±0.04,0.19±0.05,0.85±0.05 and 0.33±0.05,respectively.The differences of above indicators were statistically significant between the model group and the normal group,between the experimental-H group and the model group,as well as between the combine group and the experimental-H group(all P＜0.01).Conclusion Farrerol can improve Dox-induced myocardial injury in DCM rats,and its mechanism may be related to the activation of the CYP2J2/EETs pathway.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.