Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To study the effect of stachydrine on cardiomyocyte damage induced by high glucose(HG)and its regulation of Hippo-Yes-associated protein(YAP)signaling pathway.Methods Rat myocardial cells H9C2 were stimulated by HG with 30 mmol/L glucose to establish the myocardial cell injury model,and then treated with 0.05,0.10,0.15,0.20 mmol/L of stachydrine and their activities were detected by CCK-8 method,and the action concentration of stachycarine was screened.Then H9C2 was grouped into control(ctrl)group,HG group,low concentration stachydrine group,high concentration stachydrine group,and high concentration stachydrine+Hippo-YAP signaling pathway inhibitor(TDI-011536)group.Except for the ctrl group cultured with 5 mmol/L glucose,the other 4 groups were cultured with 30 mmol/L glucose,and the low and high concentration stachydrine groups were cultured with 0.05 and 0.10 mmol/L threonine for 24h,respectively.The high concentration stachydrine+TDI-011536 group were cultured with 0.10 mmol/L stachydrine and 3.00 μmol/L TDI-011536 for 24h.CCK-8 method was applied to detect cell proliferation.Flow cytometry was applied to detect apoptosis.ELISA were applied to detect the level of malondialdehyde(MDA)and superoxide dismutase(SOD).Western blot was applied to detect the level of phosphorylated YAP(p-YAP),YAP,proliferating cell nuclear antigen(PCNA),and B-cell lymphoma-2(Bcl-2)proteins.Results Compared with ctrl group,the survival rate of H9C2 cells induced by HG was significantly increased by 0.05,0.10,0.15,0.20 mmol/L stachydrine treatment,and the differences were statistically significant(t=8.32～29.67,all P<0.01).The 50%inhibitory concentration(IC50)value of stachydrine was about 0.09 mmol/L,and the concentrations of 0.05 mmol/L and 0.10 mmol/L close to and lower than IC50 were selected as the concentrations of hydrostachyine for subsequent experiments.Compared with the ctrl group,the survival rate in HG group was significantly decreased(t=44.32,P<0.01).Compared with HG group,the cell survival rate of low concentration stachydrine group and high concentration stachydrine group was significantly increased(t=10.06,21.66,all P<0.01).Compared with the high concentration stachydrine group,the cell survival rate in the high-concentration stachydrine+TDI-011536 group was significantly decreased(t=9.54,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,the apoptosis rate of HG group was significantly increased(t=36.74,P<0.01).Compared with HG group,the apoptosis rate of low concentration stachydrine group and high concentration stachydrine group was significantly decreased(t=11.04,26.78,all P<0.01).Compared with the high concentration threonine group,the apoptosis rate of the high concentration stachydrine+TDI-011536 group was significantly increased(t=9.96,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,SOD level in HG group was significantly decreased,MDA levels were significantly increased(t=18.85,29.12,all P<0.01).Compared with HG group,SOD level were significantly increased in low concentration stachydrine groups and high concentration stachydrine groups(t=6.59,9.86,all P<0.01),MDA level were significantly decreased(t=13.45,23.36,all P<0.01).Compared with the high concentration stachydrine group,the SOD level in the high concentration hydrostatin+TDI-011536 group was significantly decreased.MDA levels were significantly increased,and the differences were statistically significant(t=5.30,6.98,all P<0.01),respectively.Compared with ctrl group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly decreased,and the level of YAP protein was significantly increased(t=15.36～45.00,all P<0.01).Compared with HG group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly increased in low concentration stachydrine group and high concentration stachydrine group,the level of YAP protein levels were significantly decreased(t=5.51～25.15,all P<0.01).Compared with the high concentration stachydrine group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein in the high concentration hydrothreonine+TDI-011536 group were significantly decreased,the level of YAP protein significantly increased,the differences were statistically significant(t=4.27～11.25,all P<0.05).Conclusion Stachydrine may inhibit oxidative stress and apoptosis by activating Hippo-YAP signaling pathway,thereby ameliorating HG-induced myocardial cell damage.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To study the effect of stachydrine on cardiomyocyte damage induced by high glucose(HG)and its regulation of Hippo-Yes-associated protein(YAP)signaling pathway.Methods Rat myocardial cells H9C2 were stimulated by HG with 30 mmol/L glucose to establish the myocardial cell injury model,and then treated with 0.05,0.10,0.15,0.20 mmol/L of stachydrine and their activities were detected by CCK-8 method,and the action concentration of stachycarine was screened.Then H9C2 was grouped into control(ctrl)group,HG group,low concentration stachydrine group,high concentration stachydrine group,and high concentration stachydrine+Hippo-YAP signaling pathway inhibitor(TDI-011536)group.Except for the ctrl group cultured with 5 mmol/L glucose,the other 4 groups were cultured with 30 mmol/L glucose,and the low and high concentration stachydrine groups were cultured with 0.05 and 0.10 mmol/L threonine for 24h,respectively.The high concentration stachydrine+TDI-011536 group were cultured with 0.10 mmol/L stachydrine and 3.00 μmol/L TDI-011536 for 24h.CCK-8 method was applied to detect cell proliferation.Flow cytometry was applied to detect apoptosis.ELISA were applied to detect the level of malondialdehyde(MDA)and superoxide dismutase(SOD).Western blot was applied to detect the level of phosphorylated YAP(p-YAP),YAP,proliferating cell nuclear antigen(PCNA),and B-cell lymphoma-2(Bcl-2)proteins.Results Compared with ctrl group,the survival rate of H9C2 cells induced by HG was significantly increased by 0.05,0.10,0.15,0.20 mmol/L stachydrine treatment,and the differences were statistically significant(t=8.32～29.67,all P<0.01).The 50%inhibitory concentration(IC50)value of stachydrine was about 0.09 mmol/L,and the concentrations of 0.05 mmol/L and 0.10 mmol/L close to and lower than IC50 were selected as the concentrations of hydrostachyine for subsequent experiments.Compared with the ctrl group,the survival rate in HG group was significantly decreased(t=44.32,P<0.01).Compared with HG group,the cell survival rate of low concentration stachydrine group and high concentration stachydrine group was significantly increased(t=10.06,21.66,all P<0.01).Compared with the high concentration stachydrine group,the cell survival rate in the high-concentration stachydrine+TDI-011536 group was significantly decreased(t=9.54,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,the apoptosis rate of HG group was significantly increased(t=36.74,P<0.01).Compared with HG group,the apoptosis rate of low concentration stachydrine group and high concentration stachydrine group was significantly decreased(t=11.04,26.78,all P<0.01).Compared with the high concentration threonine group,the apoptosis rate of the high concentration stachydrine+TDI-011536 group was significantly increased(t=9.96,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,SOD level in HG group was significantly decreased,MDA levels were significantly increased(t=18.85,29.12,all P<0.01).Compared with HG group,SOD level were significantly increased in low concentration stachydrine groups and high concentration stachydrine groups(t=6.59,9.86,all P<0.01),MDA level were significantly decreased(t=13.45,23.36,all P<0.01).Compared with the high concentration stachydrine group,the SOD level in the high concentration hydrostatin+TDI-011536 group was significantly decreased.MDA levels were significantly increased,and the differences were statistically significant(t=5.30,6.98,all P<0.01),respectively.Compared with ctrl group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly decreased,and the level of YAP protein was significantly increased(t=15.36～45.00,all P<0.01).Compared with HG group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly increased in low concentration stachydrine group and high concentration stachydrine group,the level of YAP protein levels were significantly decreased(t=5.51～25.15,all P<0.01).Compared with the high concentration stachydrine group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein in the high concentration hydrothreonine+TDI-011536 group were significantly decreased,the level of YAP protein significantly increased,the differences were statistically significant(t=4.27～11.25,all P<0.05).Conclusion Stachydrine may inhibit oxidative stress and apoptosis by activating Hippo-YAP signaling pathway,thereby ameliorating HG-induced myocardial cell damage.

[Objective] To analyze the influence of the cycle length of hepatitis B surface antigen (HBsAg) double reagent positive samples collected from voluntary blood donors in Guangzhou on the detection results. [Methods] A total of 127 044 blood samples from voluntary blood donors at Guangzhou Blood Center from August 10 to December 9, 2023 were selected. Two ELISA reagents were used for HBsAg detection, and samples with HBsAg double reagent positive and S/CO values<10 were tested continuously for 7 days to observe the changes in their S/CO values. [Results] A total of 505 HBsAg double reagent positive samples were detected, of which 52 had S/CO values less than 10. After 7 consecutive days of uninterrupted testing, the S/CO values of Wantai (median 5 decreased to 3) and Xinchuang (median 5 decreased to 3) showed an overall downward trend, and the HBsAg missed detection rate showed an upward trend (from 0 on the first day to 1/10 000 on the seventh day). A total of 13 cases had negative double reagent test results within the 7-day testing cycle. [Conclusion] With the extension of the detection cycle, the S/CO value of HBsAg detection shows a downward trend, and the missed detection rate of HBsAg shows an upward trend. Samples used for HBsAg detection should be tested promptly after sampling to improve the quality of blood testing.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

Purpose: In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence. Materials and Methods: This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression. Results: Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence. Conclusion Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

Objective:To investigate genetic characteristics of human rhinovirus (HRV) in adult inpatients with pneumonia in autumn and winter in Bengbu, Anhui province, 2021.Methods:The pharyngeal swabs of inpatients with pneumonia in Bengbu were collected for the detection of 14 common respiratory pathogens by Real-time PCR during September to December 2021. VP4/VP2 coding regions of HRV positive samples were amplified by nested PCR and phylogenetic tree was constructed using MEGA7.0.Results:A total of 146 samples were collected from inpatients with pneumonia; 35.62% (52/146) samples were positive with at least one pathogen. The four viruses with high detection rate were HRV, adenovirus, human coronavirus OC43 and influenza B virus. HRV positive samples accounted for 44.23% (23/52) of the positive samples, among which 9 cases (39.13%, 9/23) co-infected with HRV. Phylogenetic analysis found that HRV infection were dominated by HRV-A and HRV-B groups. The analysis based on clinical syndrome found that the white blood cells count and the proportion neutrophils of patients with HRV co-infection were higher that of HRV single infection. The proportion of patients with hypertension, diabetes, mechanical ventilation and poor prognosis in the HRV co-infection group were higher than that of HRV single infection group ( P<0.05). Conclusions:HRV is the predominant pathogen among the adult inpatients with pneumonia in Bengbu. HRV-A and HRV-B groups are common. Patients accompanied by hypertension, diabetes were easily co-infected with HRV. Patients coinfeted with HRV are more likely to be mechanical ventilation and poor prognosis.

【Objective】 To explore the correlation between serological screening of human T-lymphotropic virus antibodies (anti HTLV) and Western blot(WB) confirmatory tests among blood donors, so as to explore the infection status of HTLV Ⅰ/Ⅱ in Guangzhou. 【Methods】 The anti HTLV Ⅰ/Ⅱ enzyme-linked immunosorbent assay(ELISA) kit was used to screen voluntary blood donors from Guangzhou Blood Center from July 2016 to August 2022. WB was used to confirm 395 reactive blood samples by ELISA. The correlation between the S/CO values of anti HTLV Ⅰ/Ⅱ ELISA reagents and the confirmatory test was analyzed using ROC curves. 【Results】 The results showed that 25 out of 395 initially screened reactive blood donor samples were confirmed as HTLV positive by WB, while 16 were uncertain. ROC curve analysis showed a correlation between the S/CO values by ELISA and the confirmatory test results: the S/CO value at the highest Youden index was 3.789, which was the optimal threshold. The S/CO value had a certain correlation with the predicted positive rate of confirmatory results (P<0.05): the larger the S/CO value, the higher the predicted positive value. The overall prevalence of HTLV in Guangzhou is relatively low. 【Conclusion】 The prevalence of HTLV among blood donors in Guangzhou is low.Since the false positive rate of HTLV Ⅰ/Ⅱ antibody by ELISA serological screening is high, the confirmatory testing is particularly important.