Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

Isocitrate dehydrogenase 1 (IDH1) R132H is the most common mutated gene in grade II-III gliomas and oligodendrogliomas. Instead of activating telomerase (a reverse transcriptase which using RNA as a template to extend telomere length), the majority of IDH1^R132H mutant glioma maintain telomere length through an alternative mechanism that relies on homologous recombination (HR), which is known as alterative lengthening of telomere (ALT).The phenotype of ALT mechanism include: ALT associated promyelocytic leukemia protein (PML) bodies (APBs); extrachromosomal telomeric DNA repeats such as C- and T-loops; telomeric sister chromatid exchange (T-SCE), etc. The mechanism of ALT activation is not fully understood. Recent studies have shown that mutation IDH1 contributes to ALT phenotype in glioma cells in at least three key ways. Firstly, the IDH1^R132H mutation mediates RAP1 down-regulation leading to telomere dysfunction, thus ensuring persistent endogenous telomeric DNA damage, which is important for ALT activation. Spontaneous DNA damage at telomeres may provide a substrate for mutation break-induced replication (BIR)‑mediated ALT telomere lengthening, and it has been demonstrated that RAP1 inhibits telomeric repeat-containing RNA, transcribed from telomeric DNA repeat sequences (TERRA) transcription to down-regulate ALT telomere DNA replication stress and telomeric DNA damage, thereby inhibiting ALT telomere synthesis. Similarly, in ALT cells, knockdown of telomere-specific RNaseH1 nuclease triggers TERRA accumulation, which leads to increased replication pressure. Overexpression of RNaseH1, on the other hand, attenuates the recombination capacity of ALT telomeres, leading to telomere depletion, suggesting that RAP1 can regulate the level of replication pressure and thus ALT activity by controlling TERRA expression. Secondly, the IDH1^R132H also alters the preference of the telomere damage repair pathway by down-regulating XRCC1, which inhibits the alternative non-homologous end joining (A-NHEJ) pathway at telomeres and alters cellular preference for the HR pathway to promote ALT. Finally, the IDH1^R132H has a decreased affinity for isocitric acid and NADP+ and an increased affinity for α ketoglutarate (α‑KG) and NADPH, so that the mutant IDH1^R132H catalyzes the hydrogenation of α‑KG to produce 2-hydroxyglutarate (2-HG)in a NADPH-dependent manner. Because 2-HG is structurally similar to α‑KG, which maintains the trimethylation level of H3k9me3 by competitively inhibiting the activity of the α‑KG-dependent histone demethylase KDM4B, and recruits heterochromatin protein HP1α to heterochromatinize telomeres, and promote ALT phenotypes in cooperation with the inactivating of ATRX. In addition, it has been shown that APBs contain telomeric chromatin, which is essentially heterochromatin, and HP1α is directly involved in the formation of APBs. Based on these studies, this article reviews the mechanism of IDH1^R132H mediated telomere dysfunction and the preference of DNA repair pathway at telomeres in cooperate with ATRX loss to promote ALT, which may provide references for clinical targeted therapy of IDH1^R132H mutant glioma.

Aim To study the proliferation,invasion and migration ability of Quaking(QKI)in gastric cancer(GC)via elucidating the molecular mechanisms associated with QKI in the occurrence and development of GC through bioinformatics.Methods Differential expression analysis of QKI was performed across vari-ous human cancer samples by merging data from the TCGA and GTEx databases.The correlation was ana-lyzed between QKI protein expression and tumor muta-tion burden(TMB)score,microsatellite instability(MSI)score,and ESTIMATE score,and the correla-tion was also explored between QKI protein expression and overall survival(OS),disease free survival(DFS),and progression free survival(PFS).EMT related genes that could encode DECircRNAs were ob-tained through bioinformatics analysis to construct a QKI-EMT-circRNAs regulatory network.The differenti-ally expressed circRNAs and EMT related genes in TMK1 cells were verified.The proliferation,invasion and migration ability of the QKI was studied by using the knockdown system.Results QKI was differential-ly expressed in the vast majority of tumors and was closely related to TMB,MSI,and tumor microenviron-ment(TME);QKI emerged as a high-risk factor for predicting OS,DFS,and PFS in individuals with com-mon human cancers.QKI regulated the splicing of 6 EMT related gene transcripts to form eight circRNAs,all of which were significantly associated with the prog-nosis of gastric cancer patients.Cell experiments showed that compared to normal gastric epithelial cells,only hsa_ccirc_0004015,CALD1,and CDK14 were down-regulated in TMK1 cells.Knocking down QKI inhibited the proliferation,invasion and migration ability of TMK1 cells.Conclusion QKI exerts regu-latory control over the transcription of six EMT-related genes,resulting in the formation of circRNAs,thereby promoting the pathogenesis and progression of GC.QKI is highly expressed in TMK1 cells,and knock-down of QKI can inhibit the proliferation,invasion and migration ability of TMK1 cells.

Non-alcoholic fatty liver disease (NAFLD) is considered to be a manifestation of metabolic syndrome and has become one of the chronic diseases that endanger health around the world. There is still a lack of effective therapeutic drugs in clinical practice. Farnesoid X receptor (FXR) has been a popular target for NAFLD research in recent years. Fexaramine (Fex) is a potent and selective agonist of FXR, and its mechanism of action to improve NAFLD is unclear. Therefore, in this study, a mouse model of NAFLD was constructed using a high-fat, high-cholesterol diet and treated with Fex orally for 6 weeks. We evaluated the ameliorative effect of Fex on disorders of glucolipid metabolism in NAFLD mice, and preliminarily explored its potential mechanism of action. The animal experiments were approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval number: PZSHUTCM210913011). In this study, it was found that 100 mg·kg^-1 Fex significantly inhibited body weight gain, alleviated insulin resistance, improved liver injury and lipid accumulation in NAFLD mice. The effect of Fex on the expression of hepatic intestinal FXR and its target genes in NAFLD mice was further examined. Analysis of serum and hepatic bile acid profiles and expression related to hepatic lipid metabolism. It was found that Fex could stimulate intestinal FXR, promote fibroblast growth factor 15 (FGF15) secretion, inhibit the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), the rate-limiting enzyme of bile acid synthesis in liver, regulate bile acid synthesis by negative feedback, and improve the disorder of bile acid metabolism. At the same time, Fex reduces liver lipid synthesis and absorption, increases fatty acid oxidation, thus improving liver lipid metabolism. This study shows that Fex can improve NAFLD by activating intestinal FXR-FGF15 signal pathway and regulating liver lipid metabolism.

Electronic tongue is one kind of bionic detection technologies, which can objectively reflect the taste of drugs based on electrochemical principle. In this paper, the development histories of electronic tongue both of potential type and voltammetry type were introduced, including their detection principles and key innovation technologies. In order to comprehensively improve the understanding of electronic tongue, its technological progresses, such as the study of dedicated sensors or biosensors for specific tastes, and the development of miniaturized or hybrid devices, were also discussed in detail. And the challenges and countermeasures in the application of electronic tongue were analyzed to provide some suggestions for its further technology promotion.

BACKGROUND: All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. METHODS: ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. RESULTS: We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. CONCLUSIONS Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.

Objective:To explore the differences of fecal calprotectin (FC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) between colon and small intestinal Crohn′s disease, and their predictive values for disease activity and mucosal healing in patients with small intestinal Crohn′s disease.Methods:From January 2017 to January 2023, 64 patients with Crohn′s disease who underwent capsule endoscopy in the First Affiliated Hospital of Zhejiang Chinese Medical University were enrolled, among them 28 patients had only small intestinal lesions (small intestine group) and 36 patients had lesions involving both small intestine and colon or only colon involvement (ileocolon group). The FC, CRP, and ESR levels of the two groups were detected and compared 15 days before capsule endoscopy examination. Wilcoxon rank-sum test was used for statistical analysis. Receiver operating characteristic curve analysis was used to evaluate the predictive value of FC, CRP, and ESR for disease activity and mucosal healing in patients with small intestinal Crohn′s disease.Results:The FC, CRP, and ESR levels of the small intestine group during the active phase of the disease were 1 689.00 μg/g (727.75 μg/g, 1 800.00 μg/g), 5.67 mg/L (1.00 mg/L, 17.01 mg/L), and 4.50 mm/1 h (2.00 mm/1 h, 11.00 mm/1 h), respectively; while FC, CRP, and ESR levels during the mucosal healing phase were 112.00 μg/g (46.50 μg/g, 130.50 μg/g), 1.00 mg/L (1.00 mg/L, 1.62 mg/L), and 2.00 mm/1 h (2.00 mm/1 h, 5.50 mm/1 h), respectively. The FC, CRP, and ESR levels of the ileocolon group during the active phase of the disease were 1 800.00 μg/g (895.50 μg/g, 1 800.00 μg/g), 4.94 mg/L (3.10 mg/L, 14.80 mg/L), and 10.00 mm/1 h (2.00 mm/1 h, 27.75 mm/1 h), respectively, while FC, CRP, and ESR levels during the mucosal healing phase were 66.00 μg/g (32.50 μg/g, 97.50 μg/g), 1.00 mg/L (1.00 mg/L, 1.55 mg/L), and 2.00 mm/1 h (2.00 mm/1 h, 4.50 mm/1 h), respectively. There were no statistically significant differences in FC, CRP, and ESR between the small intestine group and the ileocolon group during the active phase of the disease and mucosal healing phase (all P> 0.05). In the small intestine group, the levels of FC and CRP of patients during the active phase of the disease were 1 173.00 μg/g (312.00 μg/g, 1 800.00 μg/g) and 2.10 mg/1 L (1.00 mg/L, 16.00 mg/L), which were both higher than those of patients during the mucosal healing phase (112.00 μg/g (46.50 μg/g, 130.50 μg/g) and 1.00 mg/L (1.00 mg/L, 1.62 mg/L)), and the differences were statistically significant ( Z=-4.35 and-2.67, P<0.001 and =0.008). In the small intestine group, the level of ESR of patients during the active phase of the disease was 4.00 mm/1 h (2.00 mm/1 h, 16.00 mm/1 h), and there was no significant difference compared with that of patients during the mucosal healing phase (2.00 mm/1 h (2.00 mm/1 h, 5.50 mm/1 h)) ( P>0.05). When the cut-off level of FC was 188.50 μg/g, the sensitivity, specificity, and area under the curve for predicting disease activity in patients with small intestinal Crohn′s disease was 93.3%, 100.0%, and 0.964, respectively. When the cut-off value of CRP was 3.12 mg/L, the sensitivity, specificity, and area under the curve for predicting disease activity in patients with small intestinal Crohn′s disease was 46.7%, 92.3%, and 0.744, respectively. When the cut-off level of ESR was 10.00 mm/1 h, the sensitivity, specificity, and area under the curve for predicting disease activity in patients with small intestinal Crohn′s disease was 33.3%, 100.0%, and 0.654, respectively. There were no statistically significant differences in the area under the curve between the combinations of FC and CRP, FC and ESR, FC, CRP and ESR, and FC alone for predicting disease activity in patients with small intestinal Crohn′s disease (0.964, 0.959, and 0.959 vs. 0.964, all P> 0.05). There was a statistically significant difference in the area under the curve between the combination of CRP and ESR and FC alone in predicting disease activity in patients with small intestinal Crohn′s disease (0.708 vs. 0.964, Z=-2.57, P=0.010). Conclusions:There are no statistically significant differences in FC, CRP, and ESR between colon and small intestinal Crohn′s disease. FC has a high predictive value for disease activity and mucosal healing in patients with small intestinal Crohn′s disease and has certain clinical application value.

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

The epidemic of COVID-19 has brought great challenges to the global public health prevention and control system combined with clinical diagnosis and treatment system, and it makes the development of effective antiviral drugs an important task in current pharmaceutical research. Traditional Chinese medicine (TCM) has played an important role in the prevention and control of COVID-19. Due to its numerous chemical components and various structural types, TCM becomes a natural library for searching for lead compounds against SARS-CoV-2. In this study, a novel dual-target surface plasmon resonance (SPR) biosensor was developed for S protein receptor binding domain (SRBD) and angiotensin converting enzyme 2 (ACE2) which are two key proteins in the process of SARS-CoV-2 invading cells according to characteristics of synergistic effects of multiple components and comprehensive regulation of multiple targets of TCM. The SPR biosensor was applied to screen and identify active components from six TCMs, and daidzin from Puerariae Lobatae Radix was identified to bind with SRBD and ACE2. The affinity constant (K_D) of daidzin and ACE2 was 5.18 μmol·L^-1 through the SPR affinity assay. Competitive ELISA assay showed that daidzin could inhibit the binding of SRBD and ACE2, and the inhibition rate of daidzin (20 μmol·L^-1) was 38.6%. Molecular docking experiments further confirmed that daidzin had the best binding near the binding region of SRBD-ACE2 complex. This study shows that the dual-target SPR screening system is accurate and efficient, and is particularly suitable for screening of complex drug systems and effective substances study of TCM. It provides a material basis for exploring the mechanism of TCM active constituents against SARS-CoV-2, and provides a source of lead compounds for the development of anti-SARS-CoV-2 drugs.