ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective:Investigation of the relationship between variant angina pectoris syncope and coronary artery spastic targeted location, arrhythmias, and coronary artery stenostic lesion.Methods:This study combined retrospective and prospective registry approaches. Data were sourced from the case database of Henan province "Multicenter Clinical Observation Study of Variant Angina Pectoris". A total of 507 patients with variant angina pectoris who had complete records from June 1980 to December 2022 were consecutively enrolled. Select patients among them who experienced syncope, and analyze the target vessel sites of coronary artery spasm, arrhythmias during variant angina pectoris attacks, and the degree of stenosis in coronary artery lesions.Results:Among 507 variant angina pectoris patients, 88 experienced syncope. Age was (53.9±9.7) years and 66 patients (75.0%) were male. Forty patients (45.5%, 40/88) were aged 50-59 years. The incidence of syncope in variant angina pectoris caused by left anterior descending artery (LAD) spasm, right coronary artery (RCA) spasm, and multivessel coronary artery spasm was 7.4% (15/202), 22.7% (42/185), and 23.6% (25/106), respectively. The latter two were significantly higher than those in the LAD group ( P all<0.05). Among 77 patients with variant angina pectoris syncope, definitive electrocardiogram recordings were available during syncope episodes. All patients exhibited arrhythmias during syncope: 34 cases involved tachyarrhythmias and 43 cases involved bradyarrhythmias. The incidence of rapid arrhythmias in patients with LAD, RCA, and multi-vessel spasm syncope was 72.7% (8/11), 24.3% (9/37), and 54.2% (13/24), respectively, with P<0.05 for the first two. Bradyarrhythmias occurred in 27.3% (3/11) of LAD, 75.7% (28/37) of RCA, and 45.8% (11/24) of multivessel coronary artery spasm syncope cases, with the first two showing P<0.05. Coronary angiography analysis of 56 syncope patients revealed target vessel locations and stenosis severity: 12 patients had LAD lesions and 41 had RCA lesions, stenosis ≥50% occurred in 66.7% (8/12) and 43.9% (18/41) of these lesions, respectively ( P>0.05). Conclusions:Variant angina pectoris syncope predominantly affects middle-aged males. Bradyarrhythmias triggered by RCA spasm are a common cause, while the incidence of syncope shows no significant correlation with the degree of coronary artery stenostic lesion, whether in the LAD or the RCA.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. 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 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:Investigation of the relationship between variant angina pectoris syncope and coronary artery spastic targeted location, arrhythmias, and coronary artery stenostic lesion.Methods:This study combined retrospective and prospective registry approaches. Data were sourced from the case database of Henan province "Multicenter Clinical Observation Study of Variant Angina Pectoris". A total of 507 patients with variant angina pectoris who had complete records from June 1980 to December 2022 were consecutively enrolled. Select patients among them who experienced syncope, and analyze the target vessel sites of coronary artery spasm, arrhythmias during variant angina pectoris attacks, and the degree of stenosis in coronary artery lesions.Results:Among 507 variant angina pectoris patients, 88 experienced syncope. Age was (53.9±9.7) years and 66 patients (75.0%) were male. Forty patients (45.5%, 40/88) were aged 50-59 years. The incidence of syncope in variant angina pectoris caused by left anterior descending artery (LAD) spasm, right coronary artery (RCA) spasm, and multivessel coronary artery spasm was 7.4% (15/202), 22.7% (42/185), and 23.6% (25/106), respectively. The latter two were significantly higher than those in the LAD group ( P all<0.05). Among 77 patients with variant angina pectoris syncope, definitive electrocardiogram recordings were available during syncope episodes. All patients exhibited arrhythmias during syncope: 34 cases involved tachyarrhythmias and 43 cases involved bradyarrhythmias. The incidence of rapid arrhythmias in patients with LAD, RCA, and multi-vessel spasm syncope was 72.7% (8/11), 24.3% (9/37), and 54.2% (13/24), respectively, with P<0.05 for the first two. Bradyarrhythmias occurred in 27.3% (3/11) of LAD, 75.7% (28/37) of RCA, and 45.8% (11/24) of multivessel coronary artery spasm syncope cases, with the first two showing P<0.05. Coronary angiography analysis of 56 syncope patients revealed target vessel locations and stenosis severity: 12 patients had LAD lesions and 41 had RCA lesions, stenosis ≥50% occurred in 66.7% (8/12) and 43.9% (18/41) of these lesions, respectively ( P>0.05). Conclusions:Variant angina pectoris syncope predominantly affects middle-aged males. Bradyarrhythmias triggered by RCA spasm are a common cause, while the incidence of syncope shows no significant correlation with the degree of coronary artery stenostic lesion, whether in the LAD or the RCA.

Objective: To evaluate the mutation rates of homologous recombination repair (HRR) genes and the impact of these mutations on the clinical characteristics of metastatic endometrial cancer (EC). Methods: Somatic DNA from 895 patients with metastatic EC in the Memorial Sloan Kettering-Metastatic Events and Tropisms cohort was assessed for mutations in 10 HRR genes (BRCA1, BRCA2, ATM, BARD1, BRIP1, PALB2, RAD51C, RAD51D, CHEK2, and CDK12).The correlation between the mutation status of HRR genes and the clinical characteristics of patients with metastatic EC was evaluated. Results: Somatic mutations in HRR genes were detected in 106 (11.8%) patients with metastatic EC. Compared with nonmutation carriers, a greater proportion of carriers had endometrioid carcinoma (76.4% vs. 50.3%, p<0.001). Regarding the TCGA classification, the proportions of the POLE-ultramutated (POLEmut) and mismatch repair-deficient (dMMR) subtypes were significantly greater among mutation carriers than noncarriers (20.8% vs.0.4%, p<0.001; 34.9% vs. 11.9%, p<0.001, respectively). The carriers had a significantly lower frequency of TP53 mutations than noncarriers (25.5% vs. 54.1%, p<0.001). Fewer mutation carriers than noncarriers had intra-abdominal and lung metastases (41.5% vs.54.2%, p=0.014; 19.8% vs. 30.3%, p=0.026, respectively). The mutation status of HRR genes did not significantly affect the overall survival of patients with metastatic EC. Conclusion Somatic HRR mutations are detected in 11.8% of metastatic EC. Compared with noncarriers, HRR mutation carriers in metastatic EC have higher proportions of endometrioid carcinoma, POLEmut, and dMMR subtypes, and unique metastatic patterns.However, the prognoses are similar regardless of HRR status.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To compare the clinical efficacy between microscopic varicocelectomy and laparoscopic varicocelectomy in the treatment of varicocele(VC)with male infertility.Methods:A total of 307 patients who were diagnosed with VC complicated with male infertility and admitted to the Affiliated Hospital of Qingdao University from October 2018 to October 2022 were recruited for retrospective analysis.The patients were divided into the microscopic group(180 cases)and laparoscopic group(127 cases)according to the surgery method.The pre-and postoperative clinical data of these two groups were analyzed,including the degree of dilatation and reflux time of internal spermatic vein,hemodynamic parameters of testicular capsular artery,proportion of progressive motility spermato-zoa(PR),concentration of spermatozoa,proportion of normal morphology sperm,the pregnancy outcome of spouses and the incidence of complications related with surgery within 2 years postoperatively.Results:All the surgeries for the 307 patients in this study were successful.There was no significant difference in operation time,hospitalization time and management expenses between the microscop-ic group and the laparoscopic group(P＞0.05).Compared to the patients in laparoscopic group,the patients in the microscopic group received a better improvement in venous diameter,reflux time of spermatic veins and hemodynamic parameters of testicular capsular ar-tery(P＜0.05).Moreover,the semen analysis showed that the PR,spermatozoa concentration and proportion of normal morphology sperm in the microscopic group were also obviously increased than those in the laparoscopic group(P＜0.05).During the 2-year fol-low-up period,the conception rate of spouses in the microscopic group was 67.2％,while only 47.2％in the laparoscopic group,in which the difference was statistically significant(P＜0.05).Besides,the time-to-pregnancy(TTP)within 2 years postoperatively in the microscopic group was significantly shorter than that in the laparoscopic group(P＜0.05).Meanwhile,the incidence of adverse pregnancy outcomes in the microscopic group was also significantly lower than that in the laparoscopic group(P＜0.05).It is worth mentioned that the spontaneous conception rate of spouses with successful pregnancy in the microscopic group was also significantly higher than that in the laparoscopic group(P＜0.05).Severe complication such as testicular atrophy,bleeding and infection did not appear in both of two groups.However,the incidences of testicular hydrocele and recurrence of VC postoperatively in the laparoscopic group were significantly higher than those in the microscopic group(P＜0.05).Conclusion:Both microscopic varicocelectomy and laparoscopic varicocelectomy can be applied to the management of VC combined with male infertility.But microscopic varicocelectomy showed better clinical efficacy in improving the testicular hemodynamic parameters,semen quality,pregnancy outcome and postopera-tive complications,which is worthy of further clinical applications.

Objective To investigate the value of whole lung CT radiomics combined with clinical and conventional CT features for differentiating non-tuberculous mycobacterial pulmonary disease(NTM-PD)and pulmonary tuberculosis(PTB).Methods Fifty-three NTM-PD(NTM-PD group)and 111 PTB(PTB group)patients diagnosed by mycobacteria culture were retrospectively collected.The patients were divided into training set(n=115,including 37 cases of NTM-PD and 78 cases of PTB)and test set(n=49,including 16 cases of NTM-PD and 33 cases of PTB)at the ratio of 7∶3.Patients'clinical and pulmonary CT manifestations of lesions were analyzed using univariate and multivariate logistic regression,and the independent impact factors for differentiating NTM-PD and PTB lesions were screened.The best radiomics features were extracted and screened based on whole lung CT.Based on independent impact factors,the best radiomics features and their combination,clinical-CT,radiomics and combined models were constructed with random forest,and the differential efficacy of each model was evaluated.Results Patients'age(OR=0.264),gender(OR=0.956),immunoglobulin G(OR=3.416),C reactive protein(OR=3.418)and bronchiectasis shown on CT(OR=0.285)were all independent impact factors for differentiating NTM-PD and PTB.Twelve best radiomics features were screened based on whole lung ROI.The AUC of combined model in training set and test set was 0.915 and 0.901,respectively,both higher than that of clinical model(AUC=0.832,0.801,Z=1.340,3.710,both P＜0.05)and radiomics model(AUC=0.877,0.821,Z=-2.520,-5.240,both P＜0.05).Conclusion Whole lung CT radiomics combined with clinical and conventional CT features could effectively distinguish NTM-PD and PTB.

Objective:To explore the effectiveness and safety of different anticoagulation strategies during continuous blood purification (CBP) treatment,providing a reference for anticoagulation strategies in critically ill children undergoing CBP.Methods:A retrospective study was conducted,including children admitted to the PICU of Children's Hospital of Fudan University from January 2019 to December 2024.According to the anticoagulation methods used during CBP treatment,patients were divided into the sodium citrate group and the heparin group.CBP was performed using continuous venovenous hemofiltration or continuous venovenous hemodialysis filtration mode,with a blood flow rate of 3-5 mL/(kg·min),replacement fluid rate of 30-50 mL/(kg·h),and dialysis fluid rate of 20-30 mL/(kg·h).The filter lifespan,28-day all-cause mortality,total length of hospital stay,PICU stay duration,adverse events,and associated costs were compared between the two groups.Results:A total of 221 children were included (105 in the sodium citrate group and 116 in the heparin group),with a cumulative use of 666 filters (284 in the sodium citrate group and 382 in the heparin group).(1) There were no statistically significant differences in general data,including age,sex ratio,underlying diseases,the ratio and duration of invasive mechanical ventilation,vasopressor scores at baseline,and indications for CBP between the two groups (all P>0.05).(2) The filter lifespan was 20(14,32) hours for the sodium citrate group and 21(13,35) hours for the heparin group,with no statistically significant difference between the two groups ( P>0.05); the proportion of accidental downstroke was 2.8% and 6.5%,respectively,with a statistically significant difference ( P=0.029); among the 221 children,86 died,with 38 deaths (35.2%) in the sodium citrate group and 49 deaths (38.9%) in the heparin group,showing no statistically significant difference.(3) The sodium citrate group had a higher incidence of metabolic alkalosis,hypocalcemia,and sodium citrate accumulation (44.4% vs. 1.6%,32.7% vs 9.4%,7.7% vs 0,all P<0.01); the heparin group had a greater proportion of bleeding (6.0% vs. 2.9%) and was more likely to develop heparin-induced thrombocytopenia (10.2% vs. 0, P<0.01).(4) The total hospitalization costs for the sodium citrate group were significantly higher than for the heparin group (200 327 yuan vs. 152 077 yuan, P=0.05); costs related to the use of anticoagulants and monitoring indicators during CBP treatment were also higher in the sodium citrate group (2 479 yuan vs. 682 yuan, P<0.01). Conclusions:Sodium citrate is a safe and effective anticoagulation method for critically ill children undergoing CBP,which can reduce the risk of filter clotting compared to systemic heparin anticoagulation.