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 evaluate the effect of invasive arterial blood pressure (IBP) monitoring on the prognosis of patients with sepsis.Methods:Patients with sepsis from the MIMIC-Ⅳ database were collected and divided into IBP and non-invasive blood pressure monitoring (NIBP) groups according to whether IBP monitoring was performed. Baseline variables that were considered clinically relevant or showed a univariate relationship with the outcome were entered into a multivariate logistic regression model as covariates.Propensity score matching(PSM) and inverse probability of treatment weighing(IPTW) were used to adjust confounders to ensure the robustness of findings.Subgroup analysis were conducted to evaluate the effect of differences in IBP onset and duration on outcome.Results:The 28-day mortality is lower in IBP group compared with NIBP group( OR=0.54, 95% CI 0.46-0.62, P<0.001), the conclusion maintain robust after PSM and IPTW.Then we conducted a series of logistic regression regarding to different initial IBP time(<24 h,24 h-48 h,>48 h) and the initial IBP time within 24 h showed the same results compared to primary outcoms( OR=0.42, 95% CI: 0.36-0.49, P<0.001). IBP duration varied (≤1day, ≤2days, ≤3days, ≤4days, >4days) all showed a statistically significant association with decreased 28-day mortality in the IBP group. Conclusions:IBP is associated with decreased 28-day mortality in patients with sepsis, and the optimal time of IBP is within 24 hours.

Objective:To investigate the urine output threshold of acute kidney injury in patients with acute pancreatitis(AP) and to guide early fluid therapy.Methods:The clinical data of AP patients from Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ) were collected. The 24-h urine output rate [24-h urine output·kg-1·24-h-1, 24-UR mL/ (kg·h) ] and 48-h urine output rate [48-h urine output·kg-1·48-h-1, 48-UR mL/ (kg·h) ] were calculated, and according to the occurrence of acute kidney injury within 7 days (7-AKI), AP patients were divided into the 7-AKI group and non-7-AKI group. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of 24-UR and 48-UR on 7-AKI in AP patients. 24-UR and 48-UR were grouped according to the optimal cut-off value obtained from the ROC curve. Logistic regression was used to analyze the risk factors of 7-AKI, and Kaplan-Meier (KM) survival curve was drawn to analyze the effect of 24-UR and 48-UR on in-hospital mortality of AP patients.Results:A total of 713 AP patients were included, ROC curve analysis showed that the area under the ROC curve (AUC) of 24-UR in predicting 7-AKI in AP patients was 0.76. Based on the maximum Youden index, the cut-off value of 24-UR was 0.795 mL/ (kg·h) , and the AUC of 48-UR was 0.78 and the cut-off value of 48-UR was 0.975 mL/ (kg·h) . Logistic regression analysis showed that 24-UR≤0.795 mL/ (kg·h) was an independent risk factor for 7-AKI compared with 24-UR>0.795 mL/ (kg·h) ( OR: 4.22, 95% CI:1.50-11.85, P=0.006). Similarly, compared with 48-UR>0.975 mL/ (kg·h) , 48-UR0.975 mL/ (kg·h) was an independent risk factor for 7-AKI ( OR: 3.75, 95% CI: 1.45-9.72, P=0.007). The KM survival curve showed that the cumulative in-hospital survival rate in the high 24-UR group was higher than that in the low 24-UR group. Conclusions:24-UR can be used to guide early fluid therapy in AP patients.

Osteosarcoma needs to continuously induce angiogenesis to satisfy its own nutritional supply in the process of development. Therefore, the inhibition of osteosarcoma cell-induced angiogenesis as a target has become a research hot in recent years. Currently, vascular inhibitors targeting mRNA-encoded protein have been applied in clinic, but the efficacy is poor. Non-coding RNA (ncRNA) is a type of RNA molecules that do not participate in protein coding. ncRNA can regulate the angiogenesis of osteosarcoma by regulating the secretion of vascular factors such as vascular endothelial growth factor, angiogenin-2 and hypoxia-inducible factor 1 or the interaction between ncRNAs. This article reviews the role of ncRNA in the angiogenesis of osteosarcoma to provide references for clinical targeted therapy strategies for osteosarcoma.

Objective:To observe the expression of miR-30c-5p and Toll-like receptor 4(TLR4) in colon cancer tissues and cells, and to explore their relationship with clinicopathological features.Methods:As a prospective study, 30 cases of colon cancer surgical specimens and matched normal tissue samples were selected from the Cancer Hospital of China Medical University from May 2016 to may 2017.The expression of miR-30c-5p mRNA was detected by quantitative real-time polymerase chain reaction(qRT-PCR), and the expression of TLR4 Protein was detected by western blot (WC). The expression differences of miR-30c-5p mRNA and TLR4 protein in different TNM stages, differentiation degrees and diameters were observed.The correlation between the expression of miR-30c-5p and TLR4 Protein was analyzed by Pearson Rank method.Results:The expression of miR-30c-5p was lower in colon cancer tissues(0.311±0.147) than in adjacent normal colon tissues(0.881±0.266)( t=10.613, P<0.001). TLR4 protein was higher in colon cancer tissues(0.729±0.274) than in adjacent normal colon tissues(0.361±0.168)( t=6.310, P<0.001). Expression of miR-30c-5p was lower in colon cancer cell lines(0.394±0.045, 0.435±0.098, 0.533±0.092, 0.272±0.069) than in normal colon epithelial cell line(1.371±0.101)( t value were 6.744, 6.432, 6.865 and 6.201, respectively; P<0.001). The expression of TLR4 protein was higher in colon cancer cell lines(1.108±0.169, 1.035±0.177, 1.114±0.253, 1.116±0.157) than in normal colon epithelial tissues(0.358±0.094)( t value were 5.789, 4.799, 5.311 and 5.292, respectively; P<0.001). Pearson rank correlation showed that miR-30c-5p was negatively correlated with TLR4 protein expression( r=-0.487, 95% CI: -0.721--0.154, P<0.01). MiR-30c-5p was decreased with TNM stage increasing( F=31.406, P<0.001), pathological differentiation degree decreasing( F=9.960, P<0.001), tumor diameter increasing( F=10.267, P<0.001). TLR4 was increasing with TNM stage increasing( F=37.634, P<0.001). TLR4 increased with the decrease of tumor differentiation( F=38.027.35, P<0.001). TLR4 increased with tumor diameter ( F=20.717, P<0.001). Conclusion:The low expression of mir-30c-5p and high expression of TLR4 in colon cancer were correlated with TNM stage and tumor volume.

Objective:To investigate and compare the histologic characteristics of adenocarcinomas with mesonephric features located in different parts of the gynecologic tract.Methods:Two cases of mesonephric adenocarcinomas (MA) of the cervix and 5 cases of mesonephric-like adenocarcinomas (MLA) of the uterus and ovary were collected in Women′s Hospital, School of Medicine, Zhejiang University from January 2018 to October 2020. Hematoxylin-eosin staining, immunohistochemistry and KRAS mutation testing were performed together with review of literature.Results:MA of the cervix as well as MLA of the uterus and ovary had similar morphologic features, showing an admixture of glandular, tubular, papillary and solid growth patterns. However, both MA cases were located in cervical stroma, which demonstrated residual mesonephric ducts present at the periphery. All four uterine MLA cases extensively involved the endometrium and myometrium. The ovarian MLA case was associated with endometriosis. No residual mesonephric ducts were present in the MLA cases. Immunohistochemically, GATA3 was positive in all seven MA/MLA cases. TTF1 was expressed only in 4/5 MLA cases. ER and PR were negative and p53 was wild-type in all cases. KRAS mutation was detected in all five cases. During the 6-32 months of follow-up, one patient developed recurrence and the others were tumor-free.Conclusions:In the gynecologic tract, both MA in cervix and MLA in uterus and ovary have similar morphologic features, immunohistochemical expression and KRAS mutation. However, distinct from MA that originates from mesonephric remnant, MLA is closely related to Mullerian epithelium.

Objective:To investigate the correlation of miRNA-181b (miR-181b) and prognostic factors of myelodysplastic syndrome (MDS), to predict target gene and main biological functions of miR-181b, and to evaluate the risk prediction ability of miR-181b in MDS.Methods:The samples of 131 bone marrow in MDS patients who followed the criteria of World Health Organization (WHO) classification (2016) from the Blood Diseases Hospital, Chinese Academy of Medical Sciences between January 2019 and September 2019 were collected, and the clinical data including routine blood test results, related gene test results of blood diseases were retrospectively analyzed. The expression levels of miR-181b in all bone marrow samples were detected by using quantitative real-time polymerase chain reaction (qRT-PCR). According to the international prognostic scoring system (IPSS), WHO classification-based prognostic scoring system (WPSS) and revised IPSS (IPSS-R), the patients were divided into different groups by the risk grade, and the expression differences of miR-181b in different risk groups were compared, and the correlation between the expressions of miR-181b and partial prognostic factors, including white blood cell (WBC), hemoglobin (Hb), platelet (Plt), absolute neutrophil count(ANC), myeloblast and gene mutations was analyzed. Bioinformatics online tool TargetScan was used to make target gene prediction and the potential function of miR-181b.Results:The expression levels of miR-181b was increased with the increasing risk of IPSS, WPSS and IPSS-R, and there were statistically significant differences in miR-181b expression levels of different risk groups in different scoring systems (all P < 0.01). There was a positive correlation between the expression level of miR-181b and the scores of the three prognostic scoring systems (r was 0.437, 0.368, 0.327; all P = 0.001); miR-181b expression was positively correlated with the proportion of bone marrow myeloblasts ( r = 0.450, P < 0.01) and was negatively correlated with Plt ( r = -0.199, P = 0.024). And miR-18b was not associated with WBC, Hb, ANC, and related gene mutations of blood diseases (all P > 0.05). A total of 1 363 potential target genes of miR-181b were predicted by using bioinformatics, and biological processes of these target genes were mainly enriched in transcription regulation, RNA metabolism regulation. Among them, 22 target genes were related to the hematological malignancies, including RUNX1, ASXL2, NRAS, ATM and KRAS, which have been previously confirmed to be related to MDS. The relative expression level [the median ( P25, P75)] of miR-181b in patients who had those hematological malignancies related to miR-181b target gene mutation (32 cases) was 1.33(0.63, 1.60), which was higher than that in patients without mutation (99 cases) [0.85 (0.49, 1.38)], and the difference was statistically significant ( Z = 2.285, P = 0.022). Conclusions:miR-181b has a correlation with the risk grade of prognostic scoring systems in MDS, and it may be involved in the molecular biology pathogenesis of MDS.

Objective: To elucidate the clinicopathologic characteristics of atypical epithelioid trophoblastic lesions with cyst and fistula formation after cesarean section. Methods: The clinical and pathological data of 4 cases of post-cesarean atypical epithelioid trophoblastic lesions with cyst and fistula formation diagnosed at Women′s Hospital, School of Medicine, Zhejiang University during April 2007 to June 2018 were evaluated by hematoxylin and eosin stain and EnVision two-step immunohistochemical staining technique. Results: The age of the 4 patients ranged from 32 to 41 years, with a mean age of 36.5 years. Three patients recieved cystectomy and one underwent subtotal hysterectomy. Histologically, the lesions were well circumscribed and consisted of uniform cells of medium size, irregularly enlarged with hyperchromatic nuclei and 1 to 2 inconspicuous nucleoli embedded in abundant hyalinized matrix with fibrinoid material in the center. The cells exhibited immunohistochemical feature of chorionic-type intermediate trophoblastic cells (CK18+, p63+ and CD146-). All patients were alive without recurrence during follow-up of 1 to 40 months (mean=22 months). Conclusion Atypical epithelioid trophoblastic lesion with cyst and fistula formation after cesarean section has unique histological features, and its biological behavior and prognosis are still unclear, which need further exploration.

Objective To investigate the effect of flash glucose monitoring (FGM) on ambulatory glucose profile of only oral antidiabetic drugs treated patients with type 2 diabetes mellitus. Methods Twenty-eight type 2 diabetic mellitus patients with only oral antidiabetic drugs treatment from August 2017 to January 2018 were enrolled. All the patients were exposed to FGM for 14 d without changing the original treatment and encouraged to manage self-behavior by adjusting diet and activity based on the blood glucose data obtained from the real-time scanning. The changes in glucose profile during the FGM period were observed, including estimated glycated hemoglobin (HbA1c), standard deviation of blood glucose, variable coefficient of blood glucose, mean amplitude of glycemic excursions, time in range (blood glucose 3.9 to 10.0 mmol/L), area under the curve hyperglycemia (blood glucose> 10.0 mmol/L) and area under the curve hypoglycemia (blood glucose<3.9 mmol/L). The blood glucose levels on second day and thirteenth day were used as baseline and end point respectively. Results All of the 28 patients did not change their anti-diabetic drug therapy and there were no adverse events occurred. The estimated HbA1c was significantly lower than the baseline HbA1c: (6.90 ± 1.48)% vs. (7.57 ± 1.35)%, and there was statistical difference (P = 0.004). The standard deviation of blood glucose, variable coefficient of blood glucose, mean amplitude of glycemic excursions, area under the curve hyperglycemia and area under the curve hypoglycemia at end were significantly lower than those at baseline: (2.07 ± 0.86) mmol/L vs. (2.44 ± 0.86) mmol/L, 0.26 ± 0.11 vs. 0.30 ± 0.11, (5.32 ± 2.75) mmol/L vs. (6.76 ± 3.06) mmol/L, 265 (0, 1 310) vs. 351 (107, 2 177) and 0 (0, 0) vs. 0 (0, 19), the time in range at end was significantly higher than that at baseline: (1 069 ± 386) min vs. (921 ± 449) min, and there were statistical differences (P＜0.05 or＜0.01). The rate of scanning was (12.92 ± 4.87) times/d. Conclusions FGM could be applied by type 2 diabetic mellitus patients to make self-glycemic management without changing therapy, reduce the estimated HbA1c,and hypoglycemia, and improve the glucose fluctuations, which may result from real-time scanning to find abnormal glycemia and adjust daily behavior.

Objective To compare the effects of early passive motion(EPM)and delayed passive motion (DPM)on joint range of motion(ROM),joint function and recurrent tears after arthroscopic rotator cuff repair. Methods A total of 84 cases with middle or large rotator cuff injury were randomly divided into EPM group(43 cases)and DPM group(41 cases). EPM group began shoulder rehabilitation exercise on the first day post-opera-tion and DPM group began 6 weeks later. ROM,pain and function of shoulder joint were evaluated before and 3,6 and 12 months after operation. Results ASES score and UCLA score in EPM group were significantly higher than those in DPM group at 3 months postoperatively(P < 0.05). There was no significant difference in joint ROM,pain and functional between two groups at 6 months and 12 months postoperatively(P > 0.05). There was no statistically significant difference in recurrent tears between two groups at least 12 months follow-up. Conclusion There was no significant difference in functional outcomes,ROM and relative risks of recurrent tears between EPM and DPM in patients undergoing arthroscopic rotator cuff repairs. EPM is conducive to joint ROM and function rapid recovery postoperatively and does not increase the risks of recurrent tears.