Objective To analyze the current status and quality of existing obstetrics and gynecology enhanced recovery after surgery(ERAS)guidelines/consensus,understand the evidence-based practices in this field,and provide a basis for clinical decision-making.Methods A systematic search of PubMed,CNKI,and other databases,as well as NGC,SIGN,and websites of anesthesia societies domestically and internationally was conducted to obtain relevant guidelines and consensus on ERAS for gynecological surgery.The search was conducted from inception to July 1,2023,and the AGREE Ⅱ and RIGHT tools were used to analyze the current status and quality of the included guidelines/consensus,as well as to conduct a summary of the recommendations.Results A total of 5 guidelines and 10 consensus statements were included.The publication years were from 2018 to 2023,originating from the United States,China,Canada,and the United Kingdom.In the 6 areas evaluated using AGREEⅡ,clarity(66.06％)scored highest,followed by scope and purpose(56.67％),involvement of stakeholders(42.02％),and editorial independence(37.64％)with scores above 30％.The scores for rigor of development(26.88％)and applicability(4.17％)were relatively low.The same items among different evaluators indicated good consistency.The results of the scores in each area were as follows:A-level 2,B-level 13,and no C-level.Two high-quality guidelines were selected.The average RIGHT reporting rate was 44.38％.Subgroup analysis showed that guidelines were higher than consensus statements in the areas of rigor of development and applicability(P＜0.05),and that using GRADE was higher than not using(P＜0.05).The areas of rigor of development and clarity were higher in foreign guidelines than domestic guidelines(P＜0.05),and using evidence grading tools was higher than not using(P＜0.05).The summary of the recommendations showed that the quality of the evidence supporting the recommendations was uneven,and some recommendations were not specific enough.Conclusion The quality of the 15 included ERAS guidelines/consensus in obstetrics and gynecology is uneven,and 2 of them can be used as high-quality guidelines for clinical reference.The quality of evidence-based guidelines in foreign countries is higher,and the use rate of GRADE in foreign guidelines is high,most of which can provide clear recommendation strength and evidence level.Chinese guidelines/consensus are of lower quality compared to overseas,and methodology and report quality need further improvement.Overall,it is still necessary to strengthen the formulation of methods and reporting standards,improve the quality of evidence,and refine specific recommendations.

Objective To investigate the application value of fractional exhaled nitric oxide (FeNO), alveolar nitric oxide (CaNO), and eosinophils (EOS) in the differential diagnosis of respiratory diseases in children aged 3 to 6 years in Lanzhou, Gansu Province. Methods A total of 360 children aged 3 to 6 years with confirmed asthma, allergic rhinitis, or lower respiratory tract infection were selected as research subjects. Spearman's rank correlation coefficient was used to evaluate the correlation between FeNO, CaNO and EOS. The diagnostic value of FeNO, CaNO, and EOS for the differential diagnosis of the three diseases was assessed through random forest models, receiver operating characteristic (ROC) curves, and multivariate Logistic regression analysis. Results The median valuesof FeNO and CaNO were higher in asthmatic children than in those with other diseases. The median value of EOS was the lowest in children with allergic rhinitis, and the median values of FeNO and CaNO were the lowest in children with lower respiratory tract infection. Correlation analysis showed a positive correlation between FeNO and CaNO (r=0.59, P < 0.05), a negative correlation between FeNO and EOS (r=-0.61, P < 0.05), and a negative correlation between CaNO and EOS (r=-0.63, P < 0.05). The random forest model indicated that FeNO had the highest importance in disease classification. ROC curve analysis revealed that FeNO, CaNO, and EOS had the highest diagnostic efficiency for lower respiratory tract infection among the three diseases (with areas under the curve of 0.86, 0.91, and 1.00, respectively). The area under the curve of the multivariate Logistic regression model for diagnosing asthma was 0.96, with a sensitivity of 0.902 and a specificity of 0.881. Conclusion FeNO, CaNO and EOS demonstrate good potential in the differential diagnosis of asthma, allergic rhinitis, and lower respiratory tract infection in children aged 3 to 6 years in Lanzhou. Furthermore, the multivariate Logistic regression model based on these three factors can effectively improve the diagnostic accuracy of asthma.

Sugar-sugar glycosyltransferases play important roles in constructing complex and bioactive saponins. Here, we characterized a series of UDP-glycosyltransferases responsible for biosynthesizing the branched sugar chain of bioactive steroidal saponins from a widely known medicinal plant Paris polyphylla var. yunnanensis. Among them, a 2'-O-rhamnosyltransferase and three 6'-O-glucosyltrasferases catalyzed a cascade of glycosylation to produce steroidal diglycosides and triglycosides, respectively. These UDP-glycosyltransferases showed astonishing substrate promiscuity, resulting in the generation of a panel of 24 terpenoid glycosides including 15 previously undescribed compounds. A mutant library containing 44 variants was constructed based on the identification of critical residues by molecular docking simulations and protein model alignments, and a mutant UGT91AH1^Y187A with increased catalytic efficiency was obtained. The steroidal saponins exhibited remarkable antifungal activity against four widespread strains of human pathogenic fungi attributed to ergosterol-dependent damage of fungal cell membranes, and 2'-O-rhamnosylation appeared to correlate with strong antifungal effects. The findings elucidated the biosynthetic machinery for their production of steroidal saponins and revealed their potential as new antifungal agents.

Purpose: Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis. Materials and Methods: RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis. Results: We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties. Conclusion Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

Multiple myeloma (MM) is still an incurable hematologic malignancy, which is eagerly to the discovery of novel therapeutic targets and methods. N-acetyltransferase 10 (NAT10) is the first reported regulator of mRNA acetylation that is activated in many cancers. However, the function of NAT10 in MM remains unclear. We found significant upregulation of NAT10 in MM patients compared to normal plasma cells, which was also highly correlated with MM poor outcome. Further enforced NAT10 expression promoted MM growth in vitro and in vivo, while knockdown of NAT10 reversed those effects. The correlation analysis of acetylated RNA immunoprecipitation sequencing (acRIP-seq) and ribosome profiling sequencing (Ribo-seq) combined with RIP-PCR tests identified centrosomal protein 170 (CEP170) as an important downstream target of NAT10. Interfering CEP170 expression in NAT10-OE cells attenuated the acceleration of cellular growth caused by elevated NAT10. Moreover, CEP170 overexpression promoted cellular proliferation and chromosomal instability (CIN) in MM. Intriguingly, remodelin, a selective NAT10 inhibitor, suppressed MM cellular growth, induced cellular apoptosis in vitro and prolonged the survival of 5TMM3VT mice in vivo. Collectively, our data indicate that NAT10 acetylates CEP1 70 mRNA to enhance CEP170 translation efficiency, which suggests that NAT10 may serve as a promising therapeutic target in MM.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Objective:To determine the risk factors, clinical characteristics and treatment prognosis, so as to provide reference for clinicians to diagnose, treat and prevent drug-induced liver injury (DILI).Methods:Data of 712 confirmed DILI cases were collected from the Second Affiliated Hospital of Kunming Medical University between 2013 to 2019. Among them, 498 cases were included in the study. All patients medical history, clinical manifestations and classification, laboratory parameters, disease severity, and mortality rate were collected. Statistical analysis was performed using t-test, Mann-Whitney U test/Pearson χ2 test/Fisher's exact test or Spearman's rank test. Results:Among the suspicious drugs causing DILI, single medication accounted for 89.56%, mainly including traditional Chinese medicine (56.43%), anti-tumor and immunomodulatory agents (8.03%), anti-infective drugs (4.42%), antipyretic and analgesic drugs (4.22%) %), etc., while combination medication accounted for 10.44%. The clinical classification was dominated with hepatocyte injury (63.05%), and there was a statistically significant difference in clinical classification among age groups ( P<0.001). Age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and total bile acid (TBA) had statistically significant difference among different suspicious drugs in DILI caused by different drug ( P<0.001, 0.003, 0.001, <0.001 and <0.001). Laboratory test results showed that there were statistically significant differences in ALT, AST, ALP, γ-glutamyltransferase (GGT), TBA, international normalized ratio (INR), and eosinophils ( P<0.001, <0.001, <0.001, 0.018, 0.003 and 0.019, respectively). Chronic hepatitis was more common in the 54 cases who completed histopathological examination of the liver biopsy. Fibrosis degree was higher in the Western medicine group than Chinese herbal medicine group ( P<0.05), and the difference was statistically significant ( P<0.05). 96.99% of DILI patients were cured or improved, and 3.01% of patients were uncured. Ordinal logistic regression analysis showed that GGT and INR were independent predictors of poor prognosis. Conclusions:Suspicious drugs for DILI are herbal/dietary supplements, anti-tumor and immunomodulatory, anti-infective, and antipyretic and analgesic. The most common clinical classification is hepatocyte injury. Most patients with DILI have a good prognosis after drug withdrawal and GGT and INR are independent predictors of poor prognosis.

ObjectiveTo investigate the association of the expression of the NK cell-activating receptor NKG2D, its ligand major histocompatibility complex class I chain-related gene A (MICA), and related cytokines ［interferon-γ (IFN-γ), interleukin-10 (IL-10), and interleukin-15 (IL-15)］ with intrahepatic inflammation in primary biliary cholangitis (PBC). MethodsLiver biopsy specimens were collected from 30 patients with PBC (PBC group), 15 patients with chronic hepatitis B (CHB group), and 10 patients with nonalcoholic fatty liver disease (NAFLD group), who were hospitalized in The Second Affiliated Hospital of Kunming Medical University from August 2014 to June 2015. The degree of liver inflammation (G) and fibrosis degree (S) of the liver specimens were determined, and immunohistochemistry was used to measure the expression of NKG2D, MICA, IFN-γ, IL-10, and IL-15 in liver tissue (the scores were determined based on the number of cells stained and the degree of staining to evaluate the expression of each marker). A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the t-test was used for comparison between two groups; a Spearman correlation analysis was used to investigate correlation. ResultsIn the PBC group, the expression of NKG2D increased with the degree of inflammation, and the patients with G3-4 inflammation had significantly higher expression than those with G1-2 inflammation (G1 vs G2 vs G3 vs G4: 1.4±0.05 vs 1.56±0.05 vs 1.86±0.11 vs 2.60±0.17, F=150.8, P＜0.05); the expression of NKG2D decreased with fibrosis degree (S3 vs S4: 2.30±0.17 vs 1.56±0.05, t=-1.52, P＜0.05). In the PBC group, there was no significant difference in MICA between G3 and G4 (0.11±0.01 vs 0.20±0.03, t=-2.20, P＞0.05) and between S3 and S4 (0.12±0.02 vs 0.18±0.03, t=-2.64, P＞0.05). In the PBC group, there was a significant difference in the expression of IL-15 between the patients with different degrees of inflammation (G1 vs G2 vs G3 vs G4: 0.70±0.10 vs 1.50±0.10 vs 1.93±0.11 vs 2.60±0.17, F=251.3, P＜0.05), while there was no significant difference between the patients with different fibrosis degrees (S3 vs S4: 2.00±0.05 vs 2.40±0.30, t=-1.62, P＞0.05). In the CHB group, there was a significant difference in the expression of IL-15 between the patients with different degrees of inflammation (G1 vs G2 vs G3: 0.73±0.15 vs 1.96±0.15 vs 2.50±0.17, F=150, P＜0.05) and between the patients with different fibrosis degrees (S1 vs S2 vs S3: 0.70±0.10 vs 21.96±0.15 vs 2.50±0.17, F=158.7, P＜0.05). In the PBC group, the expression of IL-10 was only observed in the patients with G1 inflammation (0.16±0.01), and in the CHB group, the expression of IL-10 was observed in the patients with G1 and G2 inflammation, with no significant difference (G1 vs G2: 0.19±0.01 vs 0.13±0.01, t=-1.522, P＞0.05). In the patients with PBC, the expression of IL-15 in liver tissue was positively correlated with the levels of alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) (r=0.241 and 0.407, P=0.014 and 0.045). ConclusionThe NK cell-activating receptor NKG2D affects the degree of intrahepatic inflammation in PBC, and the NKG2D ligand MICA is expressed in the advanced stage of PBC and can downregulate NKG2D. The expression of IL-15 increases with the degree of inflammation in PBC and is positively correlated with the levels of ALP and GGT, suggesting that the activation of NK cells and abnormal secretion of cytokines are involved in the development and progression of PBC and IL-15 may be used as an auxiliary index for the diagnosis of PBC.

Drug-induced liver injury (DILI) has a complex pathogenesis and obvious individual difference. Early diagnosis and treatment of DILI may achieve good prognosis, but due to a lack of specific clinical symptoms, most cases cannot be identified in the early stage. If no timely treatment is given, DILI may progress to irreversible liver failure with a high mortality rate, and there are no effective therapies for advanced DILI except liver transplantation. Therefore, early diagnosis and treatment are of great importance for patients with DILI. This article summarizes the recent research advances in DILI, including suspected drugs, risk factors, pathogenesis, pathological features, clinical types and manifestations, diagnostic criteria and evaluation, and network database, in order to provide a basis for early diagnosis, clinical typing, treatment guidance, and prognostic evaluation of DILI.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive destruction of the small intrahepatic bile ducts. Patients with PBC often have extrahepatic autoimmune diseases, which can involve multiple organs and systems including the gastrointestinal tract, lung, rheumatoid immune system, and endocrine system. This article summarizes the research advances in the disease spectrum, pathogenesis, treatment, and prognosis of PBC with extrahepatic autoimmune disease.