Objective To construct and validate a prediction model for urosepsis in patients after upper urinary tract stone surgery using various machine learning algorithms.Methods A total of 7 464 upper urinary tract stone patients who underwent surgery at the Sixth Affiliated Hospital of Guangxi Medical University from Jun.2018 to Jun.2023 were enrolled and randomly assigned to training(5 224 cases)or validation sets(2 240 cases)at a ratio of 7∶3.Among them,622(8.33%)cases developed urosepsis postoperatively.Six machine learning algorithms,including extreme gradient boosting(XGBoost),logistic regression,light gradient boosting machine(LightGBM),random forest(RF),adaptive boosting(AdaBoost),and gradient boosting decision tree(GBDT),were used to construct prediction models for postoperative urosepsis.The model's predictive ability and clinical benefits were evaluated using receiver operating characteristic(ROC)curves,Shapley additive explanation(SHAP)analysis,calibration curves,and decision curve analysis(DCA).Results The clinical features included body mass index(BMI),number of surgeries,heart rate,Barthel index,venous thrombo embolism(VTE)risk assessment,gender,American Society of Anesthesiologists(ASA)grade,urinary nitrite,and urinary leukocyte in the models.In the training set,the XGBoost,LightGBM,and RF models performed excellently,with area under curve(AUC)values of ROC curves reaching 1.00.In the validation set,the logistic regression model performed the best,with an AUC value of ROC curve of 0.76,showing good predictive stability and calibration.The AdaBoost and GBDT models followed with AUC values of 0.74 and 0.75,respectively,while the AUC values of the LightGBM,XGBoost,and RF models were 0.71,0.70,and 0.68.In terms of model interpretability,SHAP analysis showed the contribution of variables in a descending order as:heart rate,urinary leukocytes,gender,BMI,Barthel index,VTE risk assessment,urinary nitrite,number of surgeries,and ASA grade.Conclusion A logistic regression model for early risk prediction of postoperative urosepsis in upper urinary tract stone patients has been successfully constructed.This model has good predictive performance and calibration,and can effectively assist clinical diagnosis.

Objective To compare the efficacy of 2 L and 3 L polyethylene glycol(PEG)electrolyte solution for bowel preparation in a real-world setting.Methods A real-world,single-center cohort study was conducted on the individuals undergoing colonoscopy in Department of Gastroenterology of Chengdu Third People's Hospital between May and October 2023.Based on our inclusion and exclusion criteria,they were given 2 L(n=4 684)and 3 L(n=3 700)PEG electrolyte solution for bowel preparation.The primary outcome indicator was the adequacy of bowel preparation by Boston bowel preparation score(BBPS).Secondary outcome indicators included the BBPS score,polyp detection rate(PDR),tolerability,compliance,and incidence of adverse events.Results The adequacy rate of bowel preparation was 94.35％in the 3 L group,significantly higher than that of the 2 L group(91.29％,P＜0.001).The 3 L group obtained a higher BBPS score then the 2 L group(6.92±1.06 vs 6.81±1.14,P＜0.001).But there was no statistical difference in the PDR between the 2 groups(P=0.073).And the rate of PEG completion(P=0.810),administration of low residue diet as required(P=0.094)or use of dimethicone(P=0.072)were comparable between the 2 groups.However,the incidences of vomiting(4.5％vs 3.2％,P=0.002),abdominal discomfort(5.0％vs 3.9％,P=0.011)and sleep disturbance(18.0％vs 14.6％,P＜0.001)were obviously higher in the 3 L group than the 2 L group.Conclusion In a real-world setting,2 L PEG is a considerably safe and effective regimen for bowel preparation.

Objective:To explore the effects of Yishen Tonglong Granules (YSTLG) on cell proliferation and apoptosis in a nude mouse model of androgen independent prostate cancer subcutaneous transplantation based on non classical Wnt signaling pathway.Methods:The tumor-bearing nude mouse model was established using the human prostate cancer bone metastatic cell line PC-3. After successful modeling, the mice were equally divided into six groups using the random number table method: model group, Western medicine group, Chinese materia medica low-, medium-, and high-dosage groups, and Chinese materia medica-Western medicine combination group. Corresponding drug interventions were administered to each group. Following 28 consecutive days of drug administration, the nude mice were euthanized. Tumor tissues were harvested for pathological observation via HE staining. Cell proliferation was assessed by immunohistochemistry; apoptosis was detected using TUNEL assay; the expressions of non-canonical Wnt signaling pathway-related proteins (Wnt5a, Rac1, RhoA, NFATc1) were analyzed through Western blot and immunohistochemical methods.Results:THE staining results demonstrated that YSTLG could effectively ameliorate pathological alterations in tumor tissues. Compared with the model group, the Chinese materia medica low-, medium-, and high-dosage groups, as well as the Chinese materia medica-Western medicine combination group, exhibited reduced proliferation indices ( P<0.01), elevated apoptosis indices ( P<0.01), down-regulated protein expressions of Wnt5a, Rac1, RhoA, and NFATc1 ( P<0.01), and decreased optical density values of Wnt5a, Rac1, RhoA, and NFATc1 ( P<0.01). These effects displayed a dosage-dependent trend. The Chinese materia medica-Western medicine combination group achieved the most pronounced therapeutic outcomes. Conclusions:YSTLG may exert inhibitory effects on the proliferation of androgen-independent prostate cancer cells and promote apoptosis, possibly through suppression of the non-canonical Wnt signaling pathway. Furthermore, its combination with Wnt signaling inhibitors may exhibit synergistic therapeutic effects.

Objective To investigate the effects and mechanism of Yuyin Qianyang Tongluo Formula on cognitive function in Alzheimer's disease mice.Methods Transgenic negative mice were designated as the normal group,while APP/PS1 double transgenic mice were randomly divided into six groups(ni=6 per group):model group,low-dose Yuyin Qianyang Tongluo Formula group,medium-dose group,high-dose group,and positive drug group.The Yuyin Qianyang Tongluo Formula low-,medium-,high-dose groups correspondingly received intragastric administration of 0.75,1.5,and 3 g·kg-1·d-1,respectively.The positive drug group received 2 mg·kg-1·d-1 donepezil hydrochloride tablets,while the model and normal groups received equal volumes of saline.All groups were treated once daily for 8 weeks.Behavioral tests were conducted using the Morris water maze and Y-maze.Hippocampal β-amyloid(Aβ)1-42 level was measured by enzyme-linked immunosorbent assay(ELISA).Hippocampal CA1 and CA3 neurons were observed hematoxylin-eosin(HE)staining,and Nissl bodies were examined Nissl staining.Protein expression levels of Aβ transporter low-density lipoprotein receptor-related protein 1(LRP-1)and endoplasmic reticulum stress marker glucose-regulated protein 78(GRP78)were detected by Western Blot analysis.Results(1)Compared with the normal group,the model group showed significantly prolonged escape latency(P＜0.000 1),reduced platform crossings,decreased movement distance and time around the platform of Morris water maze test(P＜0.05 or P＜0.01),significantly lower spontaneous alternation percentage in Y-maze test(P＜0.05),and significantly elevated hippocampal Aβ1-42 level(P＜0.000 1).Compared with the model group,all Yuyin Qianyang Tongluo Formula dose groups and the positive drug group exhibited significantly shortened escape latency of Morris water maze test(P＜0.000 1).The high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed significantly increased platform crossings,movement distance and time around the platform of Morris water maze test(P＜0.05),significantly higher spontaneous alternation percentage in Y-maze test(P＜0.05).All Yuyin Qianyang Tongluo Formula dose groups and the positive drug group showed significantly reduced hippocampal Aβ1-42 level(P＜0.000 1).(2)Compared with the normal group,the model group exhibited disordered and deformed hippocampal neurons and Nissl bodies.Compared with the model group,all Yuyin Qianyang Tongluo Formula groups and positive drug group showed improved neuronal and Nissl body organization,with the improvement degree positively correlated with dosage.(3)Compared with the normal group,the model group showed decreased LRP1 level and increased GRP78 level,but there were no statistically significant differences(P＞0.05).Compared with the model group,the high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed increased LRP1 level,while all Yuyin Qianyang Tongluo Formula dose groups and positive drug group exhibited decreased GRP78 level,but there were no statistically significant differences(P＞0.05).Conclusion Yuyin Qianyang Tongluo Formula significantly improves cognitive and memory function in model mice in a dose-dependent manner,potentially through reducing Aβ aggregation in the brain via endoplasmic reticulum stress pathway.

BACKGROUND: Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. METHODS: Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. RESULTS: A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. CONCLUSION ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Circulating Tumor DNA/blood* ; High-Throughput Nucleotide Sequencing/methods* ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; Mutation/genetics* ; Aged ; Adult ; Aged, 80 and over

Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

ObjectiveTo retrospectively analyze the association between novel coronavirus (“SARS-CoV-2”) infection and clinical symptoms in inpatients with severe acute respiratory infection (SARI) in Pudong New Area, Shanghai, so as to provide evidence for improving clinical diagnostic ability. MethodsFrom January 13 to March 2, 2023, respiratory tract specimens of 456 inpatients with SARI were collected from 8 sentinel institutions, SARS-CoV-2 was detected by real-time fluorescence quantitative PCR. Whole genome sequencing and sequence analyses were performed to samples with a cycle threshold (Ct) value of <35. At the same time, demographic information, clinical characteristics and underlying disease condition of the cases were collected, and the association between age, symptoms and nucleic acid positive rates was evaluated by χ² test and Spearman correlation analysis. ResultsA total of 456 cases were included, the median (P₂₅, P₇₅) age was 70 (69, 85) years old, of which 200 cases were novel coronavirus nucleic acid positive for SARS-CoV-2, with a positive rate of 43.86%. The positive rate was the highest in the 80-year-old group (56.82%), and the positive rate increased significantly with age (r=0.15, P=0.002). The proportion of oppression in chest, sore throat and expectoration in novel coronavirus nucleic acid positive cases was significantly higher than that in negative cases (all P<0.05). The 33 viruses sequenced successfully were all Omicron subvariants, with BF.7 (51.52%) and BA.5.2 (42.42%) being the predominant ones. ConclusionA positive correlation was observed between advanced age and the risk of SARS-CoV-2 positivity in patients with SARI. The symptoms of expectoration, oppression in chest and sore throat are more common in positive cases, which can be used as a prompt indicator for key screening and clinical identification of elderly SARI cases.