Objective:To investigate the clinicopathological features, immunohistochemical characteristics, and differential diagnosis of low-grade adenosquamous carcinoma of the breast arising from benign sclerosing lesions.Methods:Twelve cases of low-grade adenosquamous carcinoma arising from benign sclerosing lesions of the breast were collected, which were diagnosed from January 2010 to December 2023 at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital. Their clinical manifestations, histopathological morphology, and immunohistochemical characteristics were analyzed and related literatures were reviewed.Results:All the 12 patients were females with a median age of 42 years (21-60 years). Five of the 12 cases had coexisting complex sclerosing lesions, 5 with sclerosing adenosis, 1 with sclerosing intraductal papilloma, and 1 with ductal adenoma. Microscopically, low-grade adenosquamous carcinoma grew infiltratively in multinodular and sclerosing lesions. The carcinomatous component was characterized by small irregular glandular structures, tubular formations, solid nests, clusters, or a single tumor cell. The epithelium showed varying degrees of squamous differentiation. The carcinoma was surrounded by fibroadenomatoid and desmoplastic lesions. The invasive neoplastic component typically infiltrated normal breast structures, and might infiltrate nerves and adipose tissue. There were lymphocytic aggregates commonly seen at the periphery. By immunohistochemistry, the tumor cells of all 12 cases showed diffuse and strong immunopositivity for CK5/6; negative expression of ER, PR and HER2; and variable expression of myoepithelial markers such as SMA, calponin, SMMHC and others. There was varied staining pattern of tumor cells for p63. CK8/18 (or CK7) was variably positive or negative. The proliferative index measured by Ki-67 was low.Conclusions:Low-grade adenosquamous carcinoma of the breast is a rare variant, which is found to coexist with other benign sclerosing lesions and can be easily missed and/or misdiagnosed. Their invasive growth pattern, presence of sweat duct-like structures and immunophenotypic profile are key features for appropriate diagnosis.

Objective:To investigate the clinicopathological features, immunohistochemical characteristics, and differential diagnosis of low-grade adenosquamous carcinoma of the breast arising from benign sclerosing lesions.Methods:Twelve cases of low-grade adenosquamous carcinoma arising from benign sclerosing lesions of the breast were collected, which were diagnosed from January 2010 to December 2023 at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital. Their clinical manifestations, histopathological morphology, and immunohistochemical characteristics were analyzed and related literatures were reviewed.Results:All the 12 patients were females with a median age of 42 years (21-60 years). Five of the 12 cases had coexisting complex sclerosing lesions, 5 with sclerosing adenosis, 1 with sclerosing intraductal papilloma, and 1 with ductal adenoma. Microscopically, low-grade adenosquamous carcinoma grew infiltratively in multinodular and sclerosing lesions. The carcinomatous component was characterized by small irregular glandular structures, tubular formations, solid nests, clusters, or a single tumor cell. The epithelium showed varying degrees of squamous differentiation. The carcinoma was surrounded by fibroadenomatoid and desmoplastic lesions. The invasive neoplastic component typically infiltrated normal breast structures, and might infiltrate nerves and adipose tissue. There were lymphocytic aggregates commonly seen at the periphery. By immunohistochemistry, the tumor cells of all 12 cases showed diffuse and strong immunopositivity for CK5/6; negative expression of ER, PR and HER2; and variable expression of myoepithelial markers such as SMA, calponin, SMMHC and others. There was varied staining pattern of tumor cells for p63. CK8/18 (or CK7) was variably positive or negative. The proliferative index measured by Ki-67 was low.Conclusions:Low-grade adenosquamous carcinoma of the breast is a rare variant, which is found to coexist with other benign sclerosing lesions and can be easily missed and/or misdiagnosed. Their invasive growth pattern, presence of sweat duct-like structures and immunophenotypic profile are key features for appropriate diagnosis.

Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

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:To compare the consistency of microarray chemiluminescent protein chip and immunoblotting in the autoantibody spectrum of patients and the diagnostic efficacy of systemic lupus erythematosus(SLE), and to explore the correlation between the detection results of protein microarray and clinical indicators and lymphocyte subsets.Methods:Serum autoantibodies in 649 samples collected between December 2023 and December 2024 in Nanjing Drum Tower Hospital were analyzed using the microarray chemiluminescent protein chip method, with 401 samples simultaneously tested by immunoblotting. Kappa coefficient assessed inter-method consistency. Diagnostic performance was compared via ROC curves. Spearman correlation analysis evaluated relationships between autoantibody levels and SLEDAI-2000 scores, clinical parameters, and lymphocyte subsets.Results:The two methods demonstrated good consistency across 14 antinuclear antibodies, with optimal agreement for anti-SSA/Ro ( Kappa=0.845, P<0.001), anti-SSB ( Kappa=0.825, P<0.001), and anti-CENP B ( Kappa=0.851, P<0.001). The protein chip method significantly improved SLE diagnostic efficacy, particularly for anti-dsDNA (AUC difference=0.291, P<0.001) and anti-Sm antibodies (AUC difference=0.295, P<0.001). Combined detection of anti-SSA/Ro and anti-nRNP/Sm antibodies achieved superior diagnostic performance (AUC=0.927). Anti-dsDNA, anti-histone, and anti-nucleosome antibodies positively correlated with SLEDAI-2000 ( r=0.408, 0410, 0.384, all P<0.001), complement ( P<0.001), and 24-hour urinary protein ( r=0.374, 0.387, 0.301, all P<0.001). Immunological analysis showed that the proportion of NK cells was generally negatively correlated with antinuclear antibodies such as anti-dsDNA ( r=-0.352, P<0.001) and anti-Sm ( r=-0.328, P<0.001) antibodies. Meanwhile, the proportion of CD8 + T cells was positively correlated with anti-nRNP/Sm ( r=0.229, P=0.002) and anti-Sm antibodies ( r=0.211, P=0.005). The proportion of CD4 + T cells was negatively correlated with anti-SSA/Ro ( r=-0.239, P<0.001), while the proportion of B cells was positively correlated with anti-dSDNA antibody ( r=0.300, P<0.001). Conclusion:The protein chip method showed strong consistency with immunoblotting for detecting 14 autoantibodies but demonstrated superior SLE diagnostic efficacy. The combined use of multiple detection methods can enhance the reliability of clinical diagnosis.

Objective:To develop and validate a clinical prediction model for assessing the risk of postoperative pulmonary complications (PPCs) in elderly patients undergoing surgery with general anesthesia.Methods:This prospective observational study enrolled patients aged ≥65 years who underwent general anesthesia with mechanical ventilation duration >3 hours across six tertiary hospitals between December 2022 and August 2023. Based on follow-up outcomes (until discharge or postoperative day 7), patients were categorized into a non-PPCs group and a PPCs group. Detailed records included baseline patient characteristics, preoperative comorbidities, surgical information (type, duration), and bedside lung ultrasound scores (LUS) assessed within 24 hours postoperatively using a standardized 12-zone protocol. Predictor selection was performed using LASSO regression. Significant predictors identified were incorporated into a multivariate logistic regression analysis to build the prediction model, visualized as a nomogram. Internal validation was conducted via bootstrap resampling (1 000 repetitions). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) for discrimination, calibration curves for calibration accuracy, and decision curve analysis (DCA) for clinical utility.Results:A total of 130 eligible elderly surgical patients were included. PPCs occurred in 17 patients (incidence rate: 13.1%). Multivariate analysis identified LUS ( OR=1.248, 95% CI: 1.099-1.417, P=0.001) and elective surgery type ( OR=0.206, 95% CI: 0.043-0.988, P=0.048) as independent predictors of PPCs. The nomogram model demonstrated an AUC of 0.867 (95% CI: 0.775-0.959) upon initial testing. Internal validation confirmed good discrimination (AUC=0.863, 95% CI: 0.778-0.972). Calibration curves indicated excellent agreement between predicted probabilities and observed outcomes. Decision curve analysis demonstrated significant clinical net benefit across a wide range of threshold probabilities (0.03-0.89). Conclusions:The clinical prediction model, developed using early postoperative LUS scores and surgical type, effectively predicts the risk of postoperative pulmonary complications in elderly patients following surgery under general anesthesia. The model exhibits strong discrimination, calibration, and clinical utility, providing clinicians with a reliable tool for individualized risk assessment to support clinical decision-making and potentially reduce PPC incidence.

The expert consensus on the clinical treatment of herpes zoster with fire needling was developed, and the commonly used fire needling treatment scheme verified by clinical research was selected to form a standardized diagnosis and treatment scheme for acute herpes zoster and postherpetic neuralgia (PHN), so as to answer the core problems in clinical application. The consensus focuses on patients with herpes zoster, and forms recommendations for 9 key clinical issues, covering simple fire needling and TCM comprehensive therapy based on fire needling, including fire needling combined with cupping, fire needling combined with Chinese herb, fire needling combined with cupping and Chinese herb, fire needling combined with filiform needling, fire needling combined with moxibustion, and provides specific recommendations and operational guidelines for various therapies.
Humans ; Herpes Zoster/therapy* ; Acupuncture Therapy/instrumentation* ; Consensus ; Clinical Protocols

Objective To develop an ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method to simultaneously determine 10 main components, including berberine, phellodendrine, specnuezhenide, mangiferin, loganin, paeoniflorin, geniposide, baicalin, and acteoside in Compound Dihuang oral solution. Methods An UPLC-MS/MS method was established with an ACQUITY UPLC BEH-C18 （2.1 mm×100 mm, 1.7 μm）column and mobile phase of 0.1% formic water（A）-methanol solution（B） in a gradient elution manner. The flow rate of mobile phase was 0.2 ml/min.The temperature of column was 30℃. The injection volume was 2 μl. The MS detection was in MRM mode. Results 10 components in Compound Dihuang oral solution had a good linear relationship within their concentration range,and the precision, repeatability, stability and recovery met the requirements. The contents of berberine, phellodendrine, specnuezhenide, mangiferin, loganin, paeoniflorin, geniposide, baicalin, and acteoside in 7 batches of samples were （89.7-95.6） μg/ml, （164.0-177.7） μg/ml, （540.0-610.0） μg/ml, （408.7-429.0） μg/ml, （726.0-825.0） μg/ml, （503.7-572.0） μg/ml, （1380.0-1540.0） μg/ml, （2596.7-2896.7) μg/ml, （4866.7-5520.0) μg/ml, （61.8-67.2) μg/ml, respectively. Conclusion The established method was easy to be repeated and operated. The contents of 10 components in Compound Dihuang oral solution could be determined quickly and accurately, which provided a reference for the quality control of hospital preparation.