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 study the effects of vision on human postural control and the connection mechanisms of the brain's functional network.Methods 15 healthy male adults were required to perform 30 s of balanced standing on both legs with eyes open and eyes closed.The center of pressure(COP)and electroencephalograph(EEG)were recorded during balance.The sample entropy(sample En)of the COP was calculated.The phase lag index(PLI)in θ-,α-,β-band of EEG was calculated to construct the brain functional networks,and the clustering coefficient(C),characteristic path length(L),and the criteria(σ)of the small-world network were calculated based on graph theory.Results During balanced standing on both legs,the SampleEn of the COPY with eyes closed was significantly higher than that with eyes open(P＜0.05).The mean value of PLI in the α-band under the eyes closed state was significantly higher than that under the eyes open state(P＜0.05).The C and σ values in the α-band under the eyes closed state were significantly higher than those under the eyes open state,and the L value was significantly lower than that under the eyes open state(P＜0.05).The frontal-central-parietal connectivity and the central-parietal connectivity strength in the α-band under the eyes closed state were significantly higher than those under the eyes open state(P＜0.05).The average PLI and C values in the α-band were moderately negatively correlated with the SampleEn of COPY (P＜0.05).The average PLI of the left prefrontal area,left parietal area,and left occipital area in the α-band under the eyes closed state had a moderate negative correlation with the SampleEn of COPY.The average PLI of the left central region and the right occipital area in the eyes-closed state was moderately negatively correlated with the SampleEn of COPY.Conclusions During the standing balance,when there is no visual input,the stability of body balance decreases,accompanied by enhanced brain network connectivity in α-band and the requirement for efficiency enhancement in information processing in the brain.The brain adopts different neural strategies when performing postural control under various visual conditions.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.
Mice ; Animals ; Neocortex/physiology* ; Mice, Transgenic ; Interneurons/physiology*

【Objective】 To analyze ABO system hemolytic disease of the fetus and newborn (HDFN) and its influencing factors in Obstetrics Department of our hospital. 【Methods】 The blood samples of 1 040 neonates and their mothers in the obstetric department of our hospital were retrospectively analyzed from September 2022 to January 2023, including ABO and RhD blood group of the neonates and mothers, as well as 3 tests of HDFN, Hb, total bilirubin (TBIL) and indirect bilirubin(IBIL) of the neonates. Relevant clinical data of the neonates and mothers were collected, including maternal and neonatal age, neonatal sex, maternal pregnancy history, gestational age and delivery mode, and their influences on ABO-HDFN were analyzed. 【Results】 Among 1 040 HDFN samples, 298 were ABO incompatibility, among which 113 were HDFN positive, with a positive rate of 37.9% (113/298); the positive rate of HDFN in neonates born to mothers with type O was significantly higher than that in neonates born to mothers with type A and B (71.4% vs 8.2%, P<0.05); the positive rate of HDFN in neonates with antigen-A incompatibility was significantly higher than that in neonates with antigen-B incompatibility (48.7%vs 26.7%, P<0.05), which was the highest in neonates with O-A incompatibility [83.6% (61/73)], followed by O-B incompatibility [58.2% (39/67)]. There was no significant difference in Hb and bilirubin among the other groups except for the difference of Hb between the O-A incompatibility HDFN positive group and the HDFN negative group [(145.0±16.0) vs(153.4±13.2), P<0.05)]. The levels of Hb, TBIL and IBIL in the "direct antiglobulin test+ indirect antiglobulin test+release test+" group were significantly different from those in the HDFN negative group[(144.9±21.6) vs (153.3±13.2), P <0.05; (36.9±11.8) vs (29.6±6.1), P<0.05; (30.6±12.7) vs (23.0±6.9), P<0.05, respectively]. Logistic regression analysis showed that maternal delivery frequency, mother-neonate incompatible antigen and maternal blood type were independent risk factors for HDFN. 【Conclusion】 ABO-HDFN occurred mainly in neonates born to O-type mothers, and the positive rate was the highest in neonates with O-A incompatibility. The severity of HDFN had little relationship with the mother-neonate blood type, but had relationship with the result of 3 tests of HDFN. Maternal delivery frequency, mother-neonate incompatible antigen and maternal blood type were independent risk factors for HDFN.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The ubiquitin-specific peptidase 25 (USP25) protein has been reported to participate in the development of several cancers. However, few studies have reported its association with HCC. In this study, we aimed to investigate the function and mechanism of USP25 in the progression of HCC. METHODS: We analyzed USP25 protein expression in HCC based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database cohorts. Then, we constructed USP25-overexpressing and USP25-knockdown HepG2, MHCC97H, and L-O2 cells. We detected the biological function of USP25 by performing a series of assays, such as Cell Counting Kit-8 (CCK-8), colony formation, transwell, and wound healing assays. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were performed to detect the interaction between USP25 and the Wnt/β-catenin signaling pathway. The relationship between USP25 and tripartite motif-containing 21 (TRIM21) was assessed through mass spectrometry and co-immunoprecipitation (Co-IP) analysis. Finally, we constructed a mouse liver cancer model with the USP25 gene deletion to verify in vivo role of USP25. RESULTS: USP25 was highly expressed in HCC tissue and HCC cell lines. Importantly, high expression of USP25 in tissues was closely related to a poor prognosis. USP25 knockdown markedly reduced the proliferation, migration, and invasion of HepG2 and MHCC97H cells, whereas USP25 overexpression led to the opposite effects. In addition, we demonstrated that USP25 interacts with TRIM21 to regulate the expression of proteins related to epithelial-mesenchymal transition (EMT; E-cadherin, N-cadherin, and Snail) and the Wnt/β-catenin pathway (β-catenin, Adenomatous polyposis coli, Axin2 and Glycogen synthase kinase 3 beta) and those of their downstream proteins (C-myc and Cyclin D1). Finally, we verified that knocking out USP25 inhibited tumor growth and distant metastasis in vivo . CONCLUSIONS In summary, our data showed that USP25 was overexpressed in HCC. USP25 promoted the proliferation, migration, invasion, and EMT of HCC cells by interacting with TRIM21 to activate the β-catenin signaling pathway.
Animals ; Mice ; beta Catenin/genetics* ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Epithelial-Mesenchymal Transition/genetics* ; Gene Expression Regulation, Neoplastic ; Liver Neoplasms/pathology* ; Ubiquitin Thiolesterase/metabolism* ; Wnt Signaling Pathway/genetics*

Cell therapy refers to an innovative approach, in which autologous or allogeneic stem cells or differentiated somatic cells are reinfused back into the body through venous blood circulation or tissue in situ colonization after in vitro dedifferentiation or induced differentiation, culture amplification and genetic modification to achieve the goal of treating diseases by repairing or reconstructing tissues and organs, or by activating immune responses. Cell therapy leads an important paradigm shift in medical biology and marks the arrival of a new era in the history of pharmacological intervention. Compared with traditional small molecule chemical drugs and biological products, living cells are a complex organic whole involved in the body fine regulatory network and have shown great advantages and potential in clinical treatment for some complex and intractable diseases. Currently, preclinical and clinical researches on multiple innovative therapeutic strategies based on stem and immune cells are being actively optimized and explored, and have achieved many impressive results. This article reviewed the significant articles published in the field of cell therapy in 2022 from the aspects of both basic research and clinical application, summarized recent advances and major breakthroughs in stem cell therapy and immune cell therapy for the treatment of human diseases, and analyzed the challenges, hopefully powering the rapid progress in this field.

Objective To explore the safer and more reasonable time of withdrawing nucleoside analogues antiviral therapy in women with chronic HBV infection during immune tolerance period. Methods The patients included in this study were 343 pregnant women with chronic HBV infection who received nucleoside antiviral therapy in Obstetrics and Gynecology Center of 302 Military Hospital of China. According to the time of withdrawing antiviral therapy after delivery, the patients were assigned to P0 group, i.e., withdrawal immediately after delivery, and the patients who stopped the drug 6 weeks after delivery were assigned to P6w group. The patients were compared between these two groups in terms of prevalence of ALT abnormality during pregnancy and postpartum, the peak value and occurrence time of postpartum ALT, and mother-to-child vertical transmission. Results The prevalence of postpartum ALT abnormality was 30.2％ in P0 group and 20.7％ in P6w group (χ2=4.129, P=0.046). Specifically, for the patients with abnormal liver function during pregnancy, the prevalence of postpartum ALT abnormality was 88.0％ and 39.4％ in the two groups respectively (χ2=14.043, P=0.001). While for the patients with normal liver function during pregnancy, the prevalence of postpartum ALT abnormality was 19.4％ and 16.6％ respectively (χ2=0.392, P=0.531). Mother-to-infant HBV transmission was blocked successfully in all the patients in spite of the time of withdrawing antiviral therapy. Conclusions For the pregnant women with chronic HBV infection who received oral nucleoside analogue antiviral agents to interrupt motherto-child transmission, the time of withdrawing antiviral agents did not show significant effect on the prevalence of postpartum liver function abnormality and rate of successful blocking mother-toinfant HBV transmission. However, for the patients with abnormal ALT during pregnancy, it is appropriate to continue the nucleoside analogue antiviral therapy after delivery.

Objective:To establish rat diabetes and eye disease models by injection of STZ and explore the therapeutic effect of panaxnotoginseng polysaccharides (PNP) on the diabetes and eye diseases of the model rats,and to clarify their mechanisms.Methods:Seventy SD male rats were randomly divided into blank control (n=10) and model groups (n=60), and the rats in model group were fed with high fat diet. 2 weeks later, the rats in model group were intraperitoneally injected with 35 mg·kg-1 STZ to establish the models.And 3 d later, the rats were treated with fasting and water deprivation for 12 h,the fasting blood glucose (FBG)was tested, and the models were assessed to be successful as the FBG>11.1 mmol·L-1.The rats with hyperglycemia were selected and divided into model, melbine(150 mg·kg-1), and low, middle and high doses (75,150 and 300 mg·kg-1) of PNP groups.After orally administration for 5 and 8 weeks, the FBG levels of rats were recorded.And 8 weeks later, the sugar tolerance, hepatic glycogen levels,serum glutathione(GSH) and nitric oxide(NO) levels of the rats were tested.The rat retinas were removed to analyze the expression levels of vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(iNOS) by using Q-PCR.The pathological changes of retinas were observed by HE staining method.Results:Compared with model group,the FBG level in middle dose of PNP group was decreased 5 weeks after treatment(P<0.05).Eight weeks later, compared with model group, the levels of FBG, sugar tolerance and hepatic glycogen in different doses of PNP groups were all decreased (P<0.05 or P<0.01).Compared with model group, the level of serum GSH in high dose of PNP group was remarkably increased(P<0.01), and the NO level was significantly decreased (P<0.05 or P<0.01).Compared with model group, the expression levels of VEGF and iNOS in high dose of PNP group were significantly decreased (P<0.05).The results of HE staining showed that the neurodeatrophia of the rats in low and middle doses of PNP groups were improved;and the vascular proliferation and neurodeatrophia of the rats in high dose of PNP group were significantly improved.Conclusion:PNP could decrease the blood sugar, increase the levels of GSH and NO, and up-regulate the gene expression levels of VEGF and iNOS, resulting the treatment of diabetes and its related retinopathy.

Objective:To establish the rat diabetic models by introperitoneal injection of streptozotocin (STZ) to observe the expressions of MMP-2 in retina tissue of the diabetic rats at different periods,and to clarify the effect of MMP-2 in the diabetic retiropathy (DR) of the diabetic rats.Methods:The femal SD rats were divded into normal control group (n=24),4-week model group (n=30),6-week model group (n=30) and 8-week model group (n=30).The rats in model groups were intraperitoneally injected with STZ for consecutive 5 d.The rats in normal control group were injected with sodium citrate solution at the same volume.The body weights and blood glucose levels of the rats in each group were measured at 4,6,and 8 weeks.The retina of each rat was removed;RT-PCR and Western blotting methods were used to detect the expression levels of MMP-2 mRNA and protein,and the immunohistochemistry was conducted to observe the morphology.Results:The body weights and blood glucose levels of the rats in each group had no differences (P＞0.05) before modeling.Three rats died in 4-week model group,5 rats died at 6 weeks and 7 rats died at 8 weeks.The body weights of the rats in model group were significantly lower than those in normal control group at the same time (P＜0.05 or P＜0.01),and the fasting blood glucose levels were signifieantly increased (P＜0.05 or P＜0.01).The expression levels of MMP-2 mRNA and protein in the retina tissue of the rats in model group were significantly higher than those in normal control group (P＜0.05).In normal control group,the retinal structure was clear and the cells were arranged in order,and the ganglion cells were arranged in a single layer;in model group,the retinal tissue structure was loose,the number of ganglion cells were significantly reduced,the inner nuclear layer and rod cell layer cell membrane outside were fuzzy.The MMP-2 positive cells were found to be brown yellow granules,especially in the cytoplasm of ganglion cells and vascular endothelial cells.The positive expression levels of MMP-2 in model group were higher than those in normal control group at 4,6,and 8 weeks.Conclusion:MMP-2 can express in the retina tissue of the diabetic rats.