Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC _{6 months} 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC _{1 year} 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Objective To observe the expression levels and related mechanisms of miR-34a and its inflammatory-related factors in broncho-alveolar lavage fluid of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods Totally 20 patients with acute exacerbation of COPD were recruited as the study group and 20 patients in stable period of COPD were recruited as control group.Bronchoalveolar lavage fluid was collected,A549 cell was cultured and AECOPD cell model was built for evaluating the effects of over-expression of miR-34a,inhibition of miR-34a,and silencing of HIF-1α in cells.ELISA assay was applied to detect the expression of inflammatory factors IL-6,IL-8,TNF-αand TGF-β in bronchoalveolar lavage fluid and cell supernatant.The expression of miR-34a and HIF-1 αwere measured by RT-qPCR,and Western blot was used to detect the expres-sion of HIF-1α.Results Compared with the control group,the expression of inflammatory factors,miR-34a,and HIF-1α in the AECOPD group were significantly elevated(P＜0.05).Over-expression of miR-34a led to further elevation of HIF-1α and inflammatory factor expression(P＜0.05).Inhibition of miR-34a resulted in a significant decrease of HIF-1α and inflammatory factors(P＜0.05).The expression of HIF-1α in the AECOPD group was significantly elevated(P＜0.05),and silencing HIF-1α significantly reduced the expression of inflam-matory factors(P＜0.05).The expression of miR-34a had no significant change.Conclusions miR-34a is in-volved in the inflammatory damage in patients with acute exacerbation of COPD by regulating HIF-1α.Interfering with the miR-34a/HIF-1α pathway alleviates inflammatory response,so it is a potential target in the treatment of acute exacerbation of COPD.

Objective:To evaluate the efficacy of long-pulsed 1 064-nm Nd:YAG laser combined with a topical emulsion containing Camellia reticulata and Radix Notoginseng in the treatment of melasma. Methods:A total of 80 patients with melasma were enrolled from Department of Dermatology, People′s Hospital of Ningxia Hui Autonomous Region from June 2019 to June 2020, and randomly and equally divided into control group and observation group by using a random number table: 40 patients in the control group were treated with long-pulsed 1 064-nm Nd:YAG laser once every 2 weeks for 6 sessions as a course of treatment; another 40 in the observation group were treated with the same laser therapy as the control group and a topical emulsion containing Camellia reticulata and Radix Notoginseng twice a day for 3 months as a course of treatment. Melasma area and severity index (MASI), clinical efficacy, patient satisfaction rate and safety were compared between the 2 groups before and/or after treatment. Results:After 4- and 8-week treatment, there was no significant difference in the MASI score between the observation group (14.57 ± 3.22 points, 10.00 ± 2.94 points, respectively) and control group (14.74 ± 3.11 points, 11.31 ± 3.00 points, respectively; both P>0.05). After 12-week treatment, the MASI score was significantly lower in the observation group (4.80 ± 2.78 points) than in the control group (7.07 ± 3.22 points, t = -3.38, P<0.01). After 3-month treatment, the response rate was significantly higher in the observation group (36 cases, 90%) than in the control group (31 cases, 77.5%; χ2 = 4.58, P < 0.001) ; however, there was no significant difference in the patient satisfaction rate between the observation group (87.5%) and control group (72.5%, χ2 = 7.26, P = 0.06). In addition, no significant difference in the occurrence of adverse reactions was observed between the observation group (5 cases, 12.5%) and control group (7 cases, 17.5%; P > 0.05) . Conclusion:Compared with the long-pulsed 1 064-nm Nd:YAG laser alone, the topical emulsion containing Camellia reticulata and Radix Notoginseng in combination with the long-pulsed 1 064-nm Nd:YAG laser is more effective for the treatment of melasma, with higher patient satisfaction and less adverse reactions.

Objective:To analyze the spatial distribution characteristics and spatial aggregation of the epidemic of severe fever with thrombocytopenia syndrome(SFTS) in Yantai City of Shandong Province, and to provide basis for formulating effective SFTS prevention and control measures.Methods:The epidemic data of SFTS confirmed cases in each township (street) in Yantai City, Shandong Province from 2015 to 2020 were collected from the "China Disease Prevention and Control Information System Infectious Disease Monitoring and Reporting System", and ArcGIS 10.2 software was used for spatial autocorrelation analysis.Results:From 2015 to 2020, a total of 839 SFTS cases were reported in Yantai City, including 124 deaths; with an average annual incidence rate of 2.14/100 000, and a total case fatality rate of 14.78%. Global spatial autocorrelation analysis showed that the distribution of SFTS cases in Yantai City from 2015 to 2020 showed a positive spatial correlation, with the highest spatial correlation in 2015 (Moran's I = 0.25, Z = 5.66, P < 0.001), and the lowest in 2018 (Moran's I = 0.16, Z = 3.69, P < 0.001). Local spatial autocorrelation and hotspot analysis showed that the epidemic areas of SFTS were mainly in some mountainous and hilly townships (streets) of Laizhou City, Penglai District, Qixia City, Zhaoyuan City, and Haiyang City. Conclusions:The distribution of SFTS epidemic in Yantai City has obvious regional clustering. Intervention measures such as publicity, education and monitoring should be strengthened in high-incidence areas to reduce the incidence of the disease.

Background/Aims: Acute-on-chronic liver failure (ACLF) is a catastrophic illness. Few studies investigated the prognostic value of vitamin D-binding protein (VDBP) for hepatitis B virus (HBV)-related ACLF (HBV-ACLF) resulted in conflicting results. Methods: Two prospective HBV-ACLF cohorts (n=287 and n=119) were enrolled to assess and validate the prognostic performance of VDBP. Results: VDBP levels in the non-survivors were significantly lower than in the survivors (P<0.001). Multivariate Cox regression demonstrated that VDBP was an independent prognostic factor for HBV-ACLF. The VDBP level at admission gradually decreased as the number of failed organs increased (P<0.001), and it was closely related to coagulation failure. The areas under the receiver operating characteristic curve (AUCs) of the Child-Pugh-VDBP and chronic liver failuresequential organ failure assessment (CLIF–SOFA)-VDBP scores were significantly higher than those of Child-Pugh (P<0.001) and CLIF-SOFA (P=0.0013). The AUCs of model for end-stage liver disease (MELD)-VDBP were significantly higher than those of MELD (P= 0.0384) only in the case of cirrhotic HBV-ACLF patients. Similar results were validated using an external multicenter HBV-ACLF cohort. By longitudinal observation, the VDBP levels gradually increased in survivors (P=0.026) and gradually decreased in non-survivors (P<0.001). Additionally, the VDBP levels were found to be significantly decreased in the deterioration group (P=0.012) and tended to be decreased in the fluctuation group (P=0.055). In contrast, they showed a significant increase in the improvement group (P=0.036). Conclusions The VDBP was a promising prognostic biomarker for HBV-ACLF. Sequential measurement of circulating VDBP shows value for the monitoring of ACLF progression.

Osteosarcoma is a highly malignant bone tumor that predominantly affects children and adolescents. Standard chemotherapy currently used is usually poor, with a lower survival rate of patients with recurrence or metastasis. And it is necessary to find precise targeted therapy drugs from a genic perspective. This paper reviews the progress of genome research on germline mutation and somatic mutation of osteosarcoma in recent years, summarizes mutations and pathways that are closely related to osteosarcoma and can reflect the characteristics of osteosarcoma in order to provide a hope for the next generation of molecular targeted therapy.

Objective To investigate the correlation between circulating uncoupling protein 2(UCP2) level and severity of coronary artery disease(including Gensini score and criminal vessel counts)in patients with stable coronary artery disease(SCAD),and to analyze the predictive value of circulating UCP2 and urine acid (UA)for SCAD. Methods Three hundred and thirty patients from June 2015 to June 2017 were enrolled. Two hundred and forty patients with SCAD(SCAD group),90 patients without coronary artery disease(control group) were diagnosed. The circulating UCP2 level was detected by enzyme linked immunosorbent assay (ELISA) sandwich method. Results The levels of circulating UCP2 and UA in SCAD group were higher than those in the control group(UCP2[1.60(0.67,4.60)ng/mL]vs.[0.42(0.28,0.59)ng/mL](P<0.01),UA[(365.74 ± 66.06) μmol/L] vs. [(268.11 ± 45.81)μmol/L],P < 0.01). Multivariate logistic regression analysis showed that UCP2 (OR = 1.010 ,95% CI :1.001 ~ 1.020 ,P = 0.025)and UA(OR = 1.039 ,95% CI :1.007 ~ 1.072 ,P < 0.05)were independently associated with SCAD. Correlation analysis showed that the circulating UCP2 level was positively correlated with Gensini score(r=0.780,P<0.01)and criminal vessel counts(r=0.543,P<0.01). The receiver operating characteristic curve(ROC)showed that the optimal cutoff point of the circulating UCP2 level predicting SCAD was 0.64 ng/mL,and the sensitivity was 0.833 and the specificity was 0.944. No significant difference was observed in area under the curve between circulating UCP2 and UA(ΔAUC). Conclusion The high circulating UCP2 level indicates more severe coronary lesions in patients with SCAD. Circulating UCP2 level may be a new indicator of predicting SCAD,equal to the traditional oxidative stress related indicator of serum UA.

Little is known about the effects of chronic alcohol intake on the outcome of acute kidney injury (AKI). Hence, we examined the effects of chronic alcohol intake on the development of renal fibrosis following AKI in an animal model of bilateral renal ischemia–reperfusion (IR) injury. We first found that chronic alcohol exposure exacerbated bilateral IR-induced renal fibrosis and renal function impairment. This phenomenon was associated with increased bilateral IR-induced extracellular matrix deposition and an increased myofibroblast population as well as increased bilateral IR-induced expression of fibrosis-related genes in the kidneys. To explore the mechanisms underlying this phenomenon, we showed that chronic alcohol exposure enhanced β-arrestin 2 (Arrb2) expression and Akt and glycogen synthase kinase-3 (GSK3)β activation in the kidneys. Importantly, pharmacological GSK3 inhibition alleviated bilateral IR-induced renal fibrosis and renal function impairment. Furthermore, we demonstrated that Arrb2(−/−) mice exhibited resistance to IR-induced renal fibrosis and renal function impairment following chronic alcohol exposure, and these effects were associated with attenuated GSK3β activation in the kidneys. Taken together, our results suggest that chronic alcohol exposure may potentiate AKI via β-arrestin 2/Akt/GSK3β-mediated signaling in the kidney.
Acute Kidney Injury* ; Animals ; Extracellular Matrix ; Fibrosis ; Glycogen Synthase Kinase 3* ; Glycogen Synthase Kinases* ; Glycogen Synthase* ; Glycogen* ; Kidney ; Mice* ; Models, Animal ; Myofibroblasts

Isolation and characterization of metabolites produced by endophytes are significant ways to search for novel natural active substances, proving that the endophytes are the unique resources of newer and more effective compounds. Many new compounds with antimicrobial activity from different endophytes have been isolated so far. These new compounds provide alternatives to fight against multi-drug resistance of microorganisms. This review outlined the major achievements and latest developments of endophytes, including the diversity of endophytes and antimicrobial activity of endophytes, as well as its development in China.