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.

ObjectiveTo investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury （DILI）， and to establish a nomogram prediction model for validation. MethodsA retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022， and according to their clinical outcome， they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model， and calibration curve， receiver operating characteristic （ROC） curve， and decision curve analysis （DCA） were used to perform internal validation. ResultsThe univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI， platelet count， cholinesterase， albumin， prothrombin time activity， IgM， and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI （odds ratio ［OR］=0.072， 95% confidence interval ［CI］： 0.022‍ ‍—‍ ‍0.213， P<0.001）， clinical classification （OR=0.463， 95%CI： 0.213‍ ‍—‍ ‍0.926， P=0.039）， alanine aminotransferase （OR=0.999， 95%CI： 0.998‍ ‍—‍ ‍1.000， P=0.025）， prothrombin time activity （OR=0.973， 95%CI： 0.952‍ ‍—‍ ‍0.993， P=0.011）， and IgM （OR=1.456， 95%CI： 1.082‍ ‍—‍ ‍2.021， P=0.015） were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established， and after validation， the calibration curve was close to the reference curve. The area under the ROC curve was 0.829， and the DCA curve showed that the model had good net clinical benefit. ConclusionThe nomogram prediction model established in this study has good clinical calibration， discriminative ability， and application value in evaluating the clinical outcome of patients with DILI.

AIM:To explore the synergistic sensitization effect of human umbilical cord mesenchymal stem cell culture supernatant(hUMSC-CM)combined with temozolomide(TMZ)on various glioma cell lines,and to elucidate the underlying mechanisms.METHODS:The hUMSC-CM was harvested using two different serum deprivation tech-niques at 24 and 48 h,and was converted into freeze-dried powder,which was then given to rat malignant glioma cell line RG-2,human astrocytoma cell line U251 and human glioblastoma cell line LN-428 at 5 concentrations(0,1,3,6 and 9 g/L).The effectiveness and sensitivity of hUMSC-CM for inhibiting growth of glioma cells at 24,48 and 72 h were as-sessed using CCK-8 assay.Hematoxylin-eosin(HE)staining combined with CCK-8 assay was employed to evaluate the chemotherapy sensitivity of glioma cells after 48 h of treatment with TMZ at 6 concentrations(0,25,50,100,200 and 400 μmol/L).Two concentrations(3 and 9 g/L)of hUMSC-CM and 3 concentrations(50,100 and 200 μmol/L)of TMZ were chosen for concurrent treatment of glioma cells to assess the proliferation and pathological alterations.TUNEL staining was utilized to detect apoptosis.Flow cytometry was utilized to analyze cell cycle modifications.The expression alterations of apoptosis-inducing proteins,cleaved caspase-3,cleaved caspase-8 and cleaved PARP1,as well as autophagy-inducing proteins beclin-1 and LC3,were examined using Western blot to investigate the synergistic sensitization mechanism of hUMSC-CM combined with TMZ in vitro.RESULTS:The susceptibility of glioma cell lines to hUMSC-CM and TMZ varied,with RG-2 showing the highest sensitivity,followed by U251,and then LN-428.The inhibitory effect of hUMSC-CM(3 and 9 g/L)and TMZ(50,100 and 200 μmol/L)combined treatment on glioma cells was significantly greater than that that of single-agent treatments(P＜0.05),demonstrating a dose-and concentration-dependent enhancement.Notably,the combination of 9 g/L hUMSC-CM(C9)with 50 μmol/L TMZ(T50)effectively suppressed glioma cell growth.CCK-8 as-say indicated a significant reduction of cell viability in C9+T50 group compared with either C9 or T50 alone(P＜0.05).HE staining and TUNEL staining revealed pronounced morphological changes and significant apoptotic features in glioma cells treated with C9+T50.Flow cytometric analysis confirmed that C9+T50 induced cell cycle arrest in glioma cells.Fur-thermore,compared with control group,the levels of cleaved caspase-3,cleaved caspase-8,cleaved PARP1,beclin-1,and LC3-Ⅱ/LC3-Ⅰ were significantly elevated in the C9+T50-treated glioma cells(P＜0.01).CONCLUSION:(1)The concomitant administration of hUMSC-CM and TMZ exerts a broad inhibitory effect on glioma cells,with a synergistic sen-sitization observed across different cell lines.(2)The enhancement of glioma cell sensitivity to TMZ by hUMSC-CM may be attributed to the modulation of caspase-8/caspase-3/PARP1 signaling pathway and the induction of both apoptosis and autophagy in glioma cells.

ObjectiveTo evaluate the effect of the therapy of dispelling stasis， removing toxin， and promoting urination （modified Linggui Zhugantang combined with Xuebijing injection） on the prognosis of sepsis-induced cardiomyopathy （SICM）. MethodA total of 96 patients were randomly assigned into an observation group and a control group， with 48 patients in each group. The patients in the control group received sepsis bundle， and those in the observation group additionally received the therapy of dispelling stasis， removing toxin， and promoting urination （intravenous drip of Xuebijing injection and oral administration of modified Linggui Zhugantang）. The course of treatment in both groups was 7 days. The disease and prognosis indicators ［28-day mortality， intensive care unit （ICU） length of stay， major adverse cardiac events （MACE）， acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ）， sequential organ failure assessment （SOFA） score， and mortality in emergency department sepsis （MEDS） score］， cardiac function indicators ［left ventricular ejection fraction （LVEF）， E/A ratio of peak velocity blood flow from left ventricular relaxation in early diastole （the E wave） to peak velocity flow in late diastole caused by atrial contraction （the A wave）， E/e′ ratio of mitral peak velocity of early filling （E） to early diastolic mitral annular velocity （e′）， and afterload-corrected cardiac performance （ACP）］， myocardial injury markers ［high-sensitivity cardiac troponin T （hs-cTnT）， N-terminal pro-brain natriuretic peptide （NT-proBNP）， heart-type fatty acid-binding protein （H-FABP）， and high mobility group box-1 （HMGB-1）］， hemodynamic indicators ［extravascular lung water index （EVLWI）， global end-diastolic volume index （GEDVI）， cardiac index （CI）， and systemic vascular resistance index （SVRI）］， and TCM syndrome scores were assessed and compared between the two groups. ResultThe 28-day mortality and the incidence of MACE in the observation group were slightly lower than those in the control group. The ICU length of stay in the observation group was shorter than that in the control group （P<0.05）. After treatment， APACHE Ⅱ， SOFA， MEDS， syndrome score of stasis-caused internal obstruction， E/e′ ratio， hs-cTnT， NT-proBNP， H-FABP， and HMGB1 decreased compared with those before treatment （P<0.05）， while LVEF， E/A ratio， and ACP increased （P<0.05）. Moreover， the changes were more significant in the observation group （P<0.05）. On days 3， 5， and 7 after treatment， the EVLWI and SVRI in the observation group were lower than those in the control group （P<0.05）， while CI showed an opposite trend （P<0.05）. The observation group had higher GEDVI than the control group on days 3 and 5 after treatment （P<0.05）. ConclusionOn the basis of conventional bundle therapy， modified Linggui Zhugantang combined with Xuebijing injection with the effect of dispelling stasis， removing toxin， and promoting urination can inhibit the generation of myocardial injury markers and improve hemodynamics to shorten the length of ICU stay， mitigate the TCM syndrome， and reduce the risk of death， thereby improving the prognosis of SICM.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

Objective:To evaluate the left ventricular diastolic function and pulmonary congestion in patients with acute myocardial infarction (AMI) with preserved left ventricular ejection fraction (LVEF) by cardiopulmonary ultrasound (CPUS), and to explore the value of CPUS in predicting the occurrence of heart failure with preserved ejection fraction (HFpEF) in AMI patients with preserved LVEF during hospitalization.Methods:A total of eighty-four patients with AMI with preserved LVEF (≥50%) who received optimal emergency reperfusion therapy on admission at Beijing Chaoyang Hospital Affiliated to Capital Medical University from August 2021 to March 2022 were enrolled. All patients completed comprehensive cardiopulmonary ultrasonography within 12 hours after reperfusion therapy and LVEF, left atrial maximum volume(LAV), peak flow velocity of tricuspid valve regurgitation (V TR), peak flow velocity of mitral valve in early diastole (E), peak velocity of mitral valve annulus on septal side and left ventricular lateral side in early diastole and other conventional echocardiography parameters were obtained, and then the left atrial volume index (LAVI), the mean peak velocity of the mitral valve annulus on the septal side and left ventricular lateral side in early diastole (e′) and E/e′ were calculated; lung ultrasound parameters(the number of B lines) were obtained; the left ventricular global long-axis strain (GLS) was obtained using speckle tracking imaging (STE). The predictive power of CPUS parameters for HFpEF during hospitalization in AMI patients with preserved LVEF were analyzed. Results:①The incidence of HFpEF during hospitalization was 40.4% (34/84). ②The number of B lines and LAVI were independently correlated with the occurrence of HFpEF during hospitalization( P<0.05). ③The ROC curve analysis showed that the area under the curve (AUC) of the number of B lines and LAVI for predicting the occurrence of HFpEF during hospitalization were 0.766 and 0.690, respectively. The number of B lines combined with LAVI had the best predictive performance in predicting the occurrence of HFpEF during hospitalization, with the largest AUC of 0.903, which was significantly better than the number of B lines and LAVI ( P<0.05). Conclusions:The number of B lines combined with LAVI can effectively predict the occurrence of HFpEF during hospitalization in AMI patients with preserved LVEF, which is helpful to further improve the clinical management of AMI patients at risk of HFpEF.

The administration of nanoparticles (NPs) first faces the challenges of evading renal filtration and clearance of reticuloendothelial system (RES). After that, NPs infiltrate through the expanded endothelial space and penetrated the dense stroma of tumor microenvironment to tumor cells. As long as possible to prolong the time of NPs remaining in tumor tissue, NPs release active agent and induce pharmacological action. This review provides a comprehensive summary of the physical and chemical properties of NPs and the influence of various biological factors in tumor microenvironment, and discusses how to improve the final efficacy through adjusting the characteristics and structure of NPs. Perspectives and future directions are also provided.

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

Objective:To discuss the clinical and electrophysiological characteristics of propriospinal myoclonus (PSM).Methods:The clinical and electrophysiological characteristics of four patients diagnosed as PSM in the Electroencephalography Monitoring Center, Department of Neurology, Xijing Hospital, the Air Force Military Medical University from April 2018 to July 2019 were studied. All patients were accorded with diagnostic criteria of PSM that international classification of sleep disorders-3 edition recommended and were followed up.Results:There were three males and one female in the four patients. The age of onset was ranged from 43 to 55 years. The course was from eight months to three years, and the follow-up time was from three months to one year. The clinical features of the four patients were characteristically paroxysmal tic or shaking of the neck, trunk or limbs, with short duration and great frequency. All patients accepted 24-hour video electroencephalography monitoring. No epileptic discharge was recorded during the monitoring. The burst activity of deltoid, quadriceps or rectus abdominis muscle was monitored by surface electromyography at the onset of myoclonus. All patients were treated with clonazepam. Three patients had an obvious curative effect and one patient had no effect.Conclusions:The clinical manifestation of PSM is similar to seizures. There is no epileptic discharge, and only the burst activity of muscles is monitored at the onset. Most patients have significant effect on clonazepam.

OBJECTIVE: To evaluate the expression of thymidylate synthase (TS) in myoepithelial cells (MECs) of salivary adenoid tissues and explore its clinical significance. METHODS: Immunohistochemical staining EnVision method was used to detect the expression of TS, P63, Calponin, CK5/6 and S-100 in 32 salivary gland specimens, including 10 non-neoplastic and salivary inflammation specimens, 11 mixed tumor specimens, 5 basal cell carcinoma specimens and 6 adenoid cyst carcinoma specimens. The specificity and sensitivity of TS as a specific molecular marker of salivary muscle epithelial cells were evaluated in comparison with P63, Calponin, CK5/6 and S-100. RESULTS: The expression pattern of TS in all the salivary gland tissue specimens was identical with that of p63. TS and P63 both showed strong immunohistochemical expressions in MECs of salivary adenoid tissue specimens. Calponin, CK5/6, and S-100 showed cytoplasmic/membranous expressions in the MECs. In addition, TS exhibited weak or moderate cytoplasmic expression in a few salivary gland epithelial cells, cancer cells and scattered stromal cells, with negative expression in the cell nuclei. The expression of TS in the MECs of all the salivary adenoid specimens was highly consistent with those of P63, Calponin, CK5/6 and S-100 (>0.05) Except for CK5/6 expression in Salivary inflammation and Salivary gland specimens. Kappa>0.75. The specificity and sensitivity of TS as a molecular marker of MECs were both 100%. CONCLUSIONS TS is a new specific marker of MECs for differential diagnosis of salivary gland tumors.
Adenoids ; Biomarkers, Tumor ; Carcinoma, Adenoid Cystic ; Epithelial Cells ; Humans ; Salivary Gland Neoplasms ; Thymidylate Synthase