Objective:To quantitatively evaluate the effects of left bundle branch block（LBBB）on left ventricular structure，function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography（SPECT），and to investigate the relationship between myocardial work，myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy（LBBB-CM）.Methods:Fourteen male beagle dogs were selected，and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram（ECG），transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs（normal control group）matched by age and weight. The correlation between myocardial perfusion（percentage of regional tracer uptake）and myocardial work parameters，myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline，the left ventricular end-diastolic volume of 12 months after the ablation increased［（20.78 ± 5.32）ml vs（26.71 ± 7.94）ml， P = 0.003］，left ventricular ejection fraction decreased［（59.17 ± 5.67）% vs（47.69 ± 5.45）%， P<0.001］；left ventricular global/segmental longitudinal strain，global/segmental constructive work and global/segmental work efficiency decreased（all P<0.05），left ventricular global/segmental wasted work increased（all P<0.001）. Heterogenous perfusion defect was observed in LBBB dogs by SPECT，compared with lateral wall segments，the percentage of regional tracer uptake of septum was decreased（all P<0.05）. Gross anatomical and myocardial pathological changes were manifested as cardiomegaly，flaky or focal grayish thickening of endocardium，cardiomyocyte degeneration and fibrosis. Compared with normal control group，the collagen fiber volume fraction（CVF）in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased（all P<0.05）. Percentage of regional tracer uptake was positively correlated with segmental myocardial work（SMW）and segmental myocardial efficiency（SWE）（ r s = 0.49，0.31；both P<0.001），and negatively correlated with CVF and segmental wasted work（SWW）（ r s = -0.51，-0.49；both P<0.001）. Conclusions:Isolated LBBB is not benign，which can result in left ventricular remodeling，decreased cardiac constructive function，abnormal myocardial perfusion，endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion，as non-invasive examination，can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.

Objective:To quantitatively evaluate the effects of left bundle branch block（LBBB）on left ventricular structure，function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography（SPECT），and to investigate the relationship between myocardial work，myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy（LBBB-CM）.Methods:Fourteen male beagle dogs were selected，and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram（ECG），transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs（normal control group）matched by age and weight. The correlation between myocardial perfusion（percentage of regional tracer uptake）and myocardial work parameters，myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline，the left ventricular end-diastolic volume of 12 months after the ablation increased［（20.78 ± 5.32）ml vs（26.71 ± 7.94）ml， P = 0.003］，left ventricular ejection fraction decreased［（59.17 ± 5.67）% vs（47.69 ± 5.45）%， P<0.001］；left ventricular global/segmental longitudinal strain，global/segmental constructive work and global/segmental work efficiency decreased（all P<0.05），left ventricular global/segmental wasted work increased（all P<0.001）. Heterogenous perfusion defect was observed in LBBB dogs by SPECT，compared with lateral wall segments，the percentage of regional tracer uptake of septum was decreased（all P<0.05）. Gross anatomical and myocardial pathological changes were manifested as cardiomegaly，flaky or focal grayish thickening of endocardium，cardiomyocyte degeneration and fibrosis. Compared with normal control group，the collagen fiber volume fraction（CVF）in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased（all P<0.05）. Percentage of regional tracer uptake was positively correlated with segmental myocardial work（SMW）and segmental myocardial efficiency（SWE）（ r s = 0.49，0.31；both P<0.001），and negatively correlated with CVF and segmental wasted work（SWW）（ r s = -0.51，-0.49；both P<0.001）. Conclusions:Isolated LBBB is not benign，which can result in left ventricular remodeling，decreased cardiac constructive function，abnormal myocardial perfusion，endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion，as non-invasive examination，can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.

Objective To evaluate the pharmacokinetics and safety of dapoxetine hydrochloride tablets in healthy Chinese subjects,and to assess the impact of food on dapoxetine pharmacokinetics.Methods A single-center,open-lable,two-period,randomized parallel study was conducted.A total of 22 healthy adult male subjects were enrolled and administered a single 30 mg oral dose of dapoxetine hydrochloride tablets,both under fasting and fed condition.Venous blood samples were collected at different time points,and dapoxetine concentrations in human plasma were measured using liquid chromatography tandem mass spectrometry(LC-MS/MS).Pharmacokinetic parameters were calculated using Phoenix WinNonlin 6.3 software,and statistical analysis was conducted with SPSS 19.0 software.Results The main pharmacokinetic parameters after oral administration of dapoxetine hydrochloride tablets in fasting and fed were as follows:Cmax were(230.71±88.91)and(216.27±58.32)ng·mL-1;AUC0-t were(1 054.99±442.11)and(1 292.56±534.49)ng·h·mL-1;AUC0-∞ were(1 175.03±510.58)and(1 447.42±656.25)ng·h·mL-1;tmax were(1.23±0.59)and(2.40±0.90)h;t1/2 were(15.95±6.13)and(16.21±6.34)h.Comparisons between the fasting and fed states,showed statistically significant differences in AUC0-t,AUC0-∞ and tmax(all P＜0.05),but not in Cmax and t1/2(all P＞0.05).The incidence of adverse events was 31.82％in the fasting state and 22.73％in the fed state,with no significant difference(P＞0.05).Conclusion Dapoxetine hydrochloride tablets were rapidly absorbed and eliminated in both fasting and fed states,with good safety;food slowed the absorption rate of dapoxetine and increaseed its overall exposure.

Objective To explore the clinical value of red blood cell volume distribution width coefficient of variation(RDW-CV),serum interleukin-11(IL-11)and interleukin-31(IL-31)in the diagnosis of interstitial lung disease(ILD).Methods Prospectively selected 46 ILD patients admitted to the Department of Respiratory and Critical Care Medicine,the Affiliated Hospital of Chengde Medical University from November 2022 to October 2023 were set as ILD group,40 patients with community-acquired pneumonia(CAP)as CAP group,and 35 healthy examiners as control group.The ILD group was further divided into idiopathic interstitial pneumonia(IIP)subgroup(n=30)and connective tissue disease-related ILD(CTD-ILD)subgroup(n=16)based on clinical diagnosis.General and clinical data of each group were recorded,and RDW-CV and serum IL-11 and IL-31 levels were detected in each group.The ILD group was tested for alveolar arterial oxygen pressure difference(AaDO2)and arterial blood oxygen pressure(PaO2),and calculated the oxygenation index(OI).The correlation between the levels of RDW-CV,IL-11 and IL-31 and the severity of ILD were analyzed to explore the value of the above indicators in the clinical diagnosis of ILD and the differential diagnosis of different types of ILD.Results Compared with control group,there was no statistically significant difference in general information such as age,gender,smoking history,and complications between the ILD and CAP groups(P>0.05);RDW-CV,absolute values of neutrophil count(NEUT),and serum IL-11 and IL-31 levels in ILD group were significantly increased(P<0.05).Compared with CAP group,the levels of RDW-CV and serum IL-11,IL-31 in ILD group were increased,while the level of serum C-reactive protein(CRP)was decreased,with statistically significant differences(P<0.05).Correlation analysis results showed that RDW-CV and serum IL-31 in ILD patients were negatively correlated with OI(P<0.05),and positively correlated with AaDO2(P<0.05).The area under the ROC curves(AUC)of RDW-CV and serum IL-11,IL-31 single and combined applications for diagnosing ILD were 0.770,0.666,0.646,and 0.854,respectively(P<0.05).The AUC of serum IL-11 for differential diagnosis of CTD-ILD and IIP was 0.727(95%CI 0.580-0.874),with sensitivity of 62.5%and specificity of 73.3%(P<0.05).Conclusions RDW-CV and serum IL-31 have certain value in assessing the severity of ILD.RDW-CV and serum IL-11 and IL-31 have certain value in the diagnosis of ILD.Serum IL-11 has certain value in the differential diagnosis between CTD-ILD and IIP.

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.

Objective To investigate the amplitude-integrated electroencephalography(aEEG)monitoring results of hospitalized neonates in plateau areas.Methods A retrospective analysis was conducted on 5 945 neonates who were admitted to the Department of Neonatology,Kunming Children's Hospital,and received aEEG monitoring from January 2020 to December 2022.According to the aEEG monitoring results,they were divided into a normal aEEG group and an abnormal aEEG group.The incidence rate of aEEG abnormalities was analyzed in neonates with various systemic diseases,as well as the manifestations of aEEG abnormalities and the consistency between aEEG abnormalities and clinical abnormalities.Results Among the 5 945 neonates,the aEEG abnormality rate was 19.28%(1 146/5 945),with an abnormality rate of 29.58%(906/3 063)in critically ill neonates and 8.33%(240/2 882)in non-critically ill neonates(P<0.05).The children with inherited metabolic diseases showed the highest aEEG abnormality rate of 60.77%(79/130),followed by those with central nervous system disorders[42.22%(76/180)]and preterm infants[35.53%(108/304)].Compared with the normal aEEG group,the abnormal aEEG group had significantly lower age and gestational age,as well as a significantly lower birth weight of preterm infants(P<0.05).Among the 1 146 neonates with aEEG abnormalities,the main types of aEEG abnormalities were sleep cycle disorders in 597 neonates(52.09%),background activity abnormalities in 294 neonates(25.65%),and epileptiform activity in 255 neonates(22.25%),and there were 902 neonates(78.71%)with abnormal clinical manifestations.The sensitivity and specificity of aEEG monitoring for brain function abnormalities were 33.51%and 92.50%,respectively.Conclusions In plateau areas,there is a relatively high rate of aEEG abnormalities among hospitalized neonates,particularly in critically ill neonates and those with smaller gestational ages and younger ages,suggesting a high risk of brain injury.Therefore,routine aEEG monitoring for the hospitalized neonates can help with the early detection of brain function abnormalities,the decision-making in treatment,and the formulation of brain protection strategies.

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

Objective To assess the levels of peripheral blood markers including carbohydrate antigen 15-3(CA15-3),carbohydrate antigen 125(CA125),carcinoembryonic antigen(CEA),cytokeratin-18(CK18),and neutrophil-to-lymphocyte count ratio(NLR)in breast cancer patients,investigate their correlation with clinico-pathological characteristics,and evaluate the impact of neoadjuvant chemotherapy.Methods The clinical data of 187 patients with breast cancer who underwent neoadjuvant chemotherapy at our hospital between January 2020 and December 2023 were retrospectively analyzed.Based on the evaluation criteria for solid tumor response after 8 cycles of chemotherapy,the patients were divided into two groups:an effective group(n=84)and an ineffective group(n=103).The levels of CA15-3,CA125,CEA,CK18,and NLR in the peripheral blood of breast cancer patients before neoadjuvant chemotherapy were measured.Furthermore,a comparison was made between the levels of CA15-3,CA125,CEA,CK18,and NLR in the peripheral blood among breast cancer patients with different clinicopathological characteristics.Additionally,a comparison was conducted between the levels of CA15-3,CA125,CEA,CK18,and NLR in the peripheral blood as well as clinical data between the effective group and in-effective group.Univariate and multivariate logistic regression analyses were employed to examine the factors influ-encing the ineffectiveness of neoadjuvant chemotherapy in breast cancer patients.Additionally,a receiver operating characteristic(ROC)curve was constructed to assess the predictive efficacy of peripheral blood markers including CA15-3,CA125,CEA,CK18,and NLR on the response to neoadjuvant chemotherapy in breast cancer patients.Results The levels of CA15-3,CA125,CEA,CK18,and NLR in the peripheral blood of breast cancer patients with T3～T4 stage,N1～N3 stage,and human epidermal growth factor receptor-2(HER-2)positivity were signifi-cantly elevated compared to those in breast cancer patients with T2 stage,N0 stage,and HER-2 negativity(P＜0.05).The levels of CA15-3,CA125,CEA,CK18,and NLR in the peripheral blood were found to be higher in the ineffective group than in the effective group(P＜0.05).Moreover,a higher proportion of patients in the inef-fective group exhibited T3～T4 stage tumors along with N1～N3 lymph node involvement.Additionally observed were histological grade of low differentiation as well as positive progesterone receptor and estrogen receptor expression.Furthermore high expression of tumor proliferation antigen was more prevalent among patients classified under the ineffective group.(P＜0.05).Elevated peripheral blood CA15-3,CA125,CEA,CK18 and NLR levels,T3～T4 stage,N1～N3 stage,low differentiation,and ER positive were identified as significant risk factors for neoadjuvant chemotherapy in breast cancer patients(P＜0.05).The predictive performance of peripheral blood CA15-3,CA125,CEA,CK18 and NLR in assessing the efficacy of neoadjuvant chemotherapy yielded a sensitivity of 96.43%,specificity of 82.52%,and an area under the curve(AUC)value of 0.956.Furthermore,combined pre-diction demonstrated higher sensitivity and AUC compared to individual predictors(P＜0.05),while maintaining similar specificity levels.Conclusions The levels of CA15-3,CA125,CEA,CK18 and NLR in peripheral blood are closely associated with the clinicopathological characteristics of breast cancer patients and can impact the effi-cacy of neoadjuvant chemotherapy.These biomarkers have potential for predicting response to neoadjuvant chemo-therapy in breast cancer patients,with improved accuracy when used in combination.

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 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.