Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

OBJECTIVE: To construct a predictive model for the reduction in methadone maintenance treatment (MMT) and evaluate the effects of different interventions and other clinical factors on methadone reduction using Shapley additive explanations (SHAP). METHODS: Two clinical trials of acupuncture for methadone reduction in MMT patients were analyzed, and the baseline data, MMT related information, intervention measures, the data related to dose-reduction outcomes were collected. The predictive model was constructed by means of 6 machine learning algorithms including support vector machine (SVM), K-nearest neighbors (KNN), logistic regression (LR), Naive Bayes (NB), random forest (RF) and categorical-boosting (CatBoost), and 2 integration methods, blending-ensemble method (Blending) and Stacking-ensemble method (Stacking). SHAP was employed for the interpretability analysis of the optimal model. RESULTS: A total of 251 MMT patients were included, 128 cases in the acupuncture group and 123 cases in the non-acupuncture group. CatBoost and Stacking performed optimally in the test set. CatBoost obtained an accuracy of 0.780 0±0.060 8, a precision of 0.500 0±0.120 0, a recall of 0.818 2±0.140 2, F1 score of 0.620 7±0.114 0, and receiver operating characteristic-area under curve (ROC-AUC) of 0.857 8±0.140 2 for the subjects. In MMT patients with acupuncture as an adjunctive therapy, the top 5 important features for methadone reduction, included intervention measures, body mass index (BMI), the duration of MMT, the history of opioid use and occupation; and SHAP values were 1.25, 0.36, 0.21, 0.19 and 0.12, respectively. The SHAP feature dependence plot showed that BMI, MMT duration and the history of opioid use presented a nonlinear negative correlation with the reduction effect. CONCLUSION In acupuncture as adjunctive therapy for methadone reduction, the clinical factors should be considered comprehensively; and the interpretable predictive model provides a scientific basis for it, which is conducive to the improvement of clinical strategy of acupuncture for methadone reduction and the development of personalized reduction scheme.
Humans ; Methadone/therapeutic use* ; Acupuncture Therapy ; Adult ; Female ; Male ; Machine Learning ; Middle Aged ; Opiate Substitution Treatment ; Young Adult

Most of the current research on depression focuses on neuronal regulation,while the astrocytic mechanism of depression is far from explored.Astrocytes are the most numerous and widely distributed glial cells in the central nervous system.With a complex structural morphology,astrocytes play an important role in a variety of neuropsychiatric disorders by interacting with neuronal synapses,vasculature and other glial cells.Recent studies have shown that astrocytes may be involved in depression by regulating monoamine transmitters,glutamate cycle,synaptic plasticity,energy metabo-lism,and neuroinflammation.This review is intended to inspire new ideas for the treatment of depres-sion and the development of novel drugs based on astrocyte regulation.

Intracellular overexpression of cytoglobin (Cygb) has been shown to reduce extracellular matrix deposition and promote liver fibrosis recovery, but its mechanism is not yet clear. This study constructed and expressed a fusion protein (TAT-Cygb) of cell penetrating peptide TAT and Cygb, to investigate the effect of fusion protein TAT-Cygb on regulating hepatic stellate cells (HSCs) ferroptosis. Cultured human hepatic stellate cells line (LX2) were treated with TAT-Cygb and erastin in vitro, respectively. The effects of ferroptosis phenotype in LX2 cells induced by TAT-Cygb, including cell viability, cell morphology, iron ion (Fe²⁺) content, lipid peroxidation product levels, and antioxidant system indicators, were investigated using trypan blue staining, transmission electron microscopy, Prussian blue staining, and reagent kits detection. After co-treatment with TAT-Cygb and ferrostain-1, the levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) were measured by reagent kits. The protein expression levels of alpha smooth actin (α-SMA), collagen I and fibronectin were detected by Western blot, and the protein expression level of epidermal growth factor receptor (EGFR) and desmin relevant to fibrosis were observed by immunofluorescence. The results showed that TAT-Cygb could significantly reduce the viability of LX2 cells and trigger events relevant to ferroptosis, including promoting intracellular Fe²⁺ accumulation, and inducing mitochondrial morphological changes, and intensifying lipid peroxidation products accumulation, and decreasing the level of antioxidant indexes, which played a similar role as erastin; Fer-1 significantly weakened the increase in Fe²⁺, ROS, MDA, 4-HNE levels induced by TAT-Cygb, as well as the decrease in NADPH and GSH levels, while also weakening the TAT-Cygb-induced over-expression levels of α-SMA, collagen I and fibronectin, and TAT-Cygb-induced under-expression levels of EGFR and desmin. This cellular level study indicated that TAT-Cygb can induce ferroptosis of activated HSCs. This study revealed the potential mechanism of TAT-Cygb anti-liver fibrosis, and provided the experimental basis for further research on the molecular mechanism of TAT-Cygb realizing biological function by regulating the ferroptosis pathway.

Objective:To analyze the correlation between serum interleukin-6 (IL-6) and osteopontin (OPN) levels and bone metabolism markers in pregnant women with gestational diabetes mellitus.Methods:A total of 89 pregnant women with GDM who were admitted to Shanxi Children’s Hospital from Aug. 2020 to May. 2022 were selected as the observation group, and 85 normal pregnant women who underwent regular health examination were selected as the control group. Clinical data of the two groups were compared and GDM related factors were analyzed. Serum IL-6, OPN, bone metabolic markers β collagen special sequence (β-CTX), type I procollagen N-terminal propeptide (PINP), n-terminal mid-section osteocalcin (N-MID), fasting blood glucose (FBG) and fasting insulin (FINS) levels of the two groups were detected. Insulin resistance index (HOMA-IR) was calculated, and the relationship between serum IL-6, OPN and β-CTX, PINP and N-MID was analyzed.Results:The age, gestational times and pre-pregnancy BMI of the observation group were higher than those of the control group, and the family history of diabetes was more than that of the control group, with statistical significance between the two groups ( t=14.31, 31.46, 9.47, 10.33, P<0.05). Logistic regression analysis showed that the older the age and the more pregnancies, the higher the pre-pregnancy BMI. Independent risk factors for developing GDM were associated with a large family history of diabetes mellitus [ ( OR (95% CI) =1.569 (1.370-1798), 8.533 (5.067-14.367), 1.460 (1.301-1.639), 3.677 (1.611-8.396). P<0.05) ]; Serum levels of IL-6, OPN, FBG, FINS and HOMA-IR in observation group were higher than those in control group ( t=16.64, 24.76, 10.97, 11.01, 55.70, all P<0.05). The β-CTX of observation group was higher than that of control group, and the PINP and N-MID of observation group were lower than that of control group ( t=3.64, 12.19, 12.52, P<0.05). Spearman correlation analysis showed that serum IL-6 and OPN were positively correlated with β-CTX ( r=0.781, 0.746, P<0.05). Serum IL-6 and OPN were negatively correlated with PINP and N-MID ( r=-0.264, -0.305; -0.208, -305, P<0.05) . Conclusions:In pregnant women with GDM, serum IL-6 and OPN are positively correlated with β-CTX, and serum IL-6 and OPN are negatively correlated with PINP and N-MID, respectively. These indicators can be used as indicators of disease monitoring, and play an important role in protecting the health of pregnant women with GDM.

Objective:To analyze the correlation between serum interleukin-6 (IL-6) and osteopontin (OPN) levels and bone metabolism markers in pregnant women with gestational diabetes mellitus.Methods:A total of 89 pregnant women with GDM who were admitted to Shanxi Children’s Hospital from Aug. 2020 to May. 2022 were selected as the observation group, and 85 normal pregnant women who underwent regular health examination were selected as the control group. Clinical data of the two groups were compared and GDM related factors were analyzed. Serum IL-6, OPN, bone metabolic markers β collagen special sequence (β-CTX), type I procollagen N-terminal propeptide (PINP), n-terminal mid-section osteocalcin (N-MID), fasting blood glucose (FBG) and fasting insulin (FINS) levels of the two groups were detected. Insulin resistance index (HOMA-IR) was calculated, and the relationship between serum IL-6, OPN and β-CTX, PINP and N-MID was analyzed.Results:The age, gestational times and pre-pregnancy BMI of the observation group were higher than those of the control group, and the family history of diabetes was more than that of the control group, with statistical significance between the two groups ( t=14.31, 31.46, 9.47, 10.33, P<0.05). Logistic regression analysis showed that the older the age and the more pregnancies, the higher the pre-pregnancy BMI. Independent risk factors for developing GDM were associated with a large family history of diabetes mellitus [ ( OR (95% CI) =1.569 (1.370-1798), 8.533 (5.067-14.367), 1.460 (1.301-1.639), 3.677 (1.611-8.396). P<0.05) ]; Serum levels of IL-6, OPN, FBG, FINS and HOMA-IR in observation group were higher than those in control group ( t=16.64, 24.76, 10.97, 11.01, 55.70, all P<0.05). The β-CTX of observation group was higher than that of control group, and the PINP and N-MID of observation group were lower than that of control group ( t=3.64, 12.19, 12.52, P<0.05). Spearman correlation analysis showed that serum IL-6 and OPN were positively correlated with β-CTX ( r=0.781, 0.746, P<0.05). Serum IL-6 and OPN were negatively correlated with PINP and N-MID ( r=-0.264, -0.305; -0.208, -305, P<0.05) . Conclusions:In pregnant women with GDM, serum IL-6 and OPN are positively correlated with β-CTX, and serum IL-6 and OPN are negatively correlated with PINP and N-MID, respectively. These indicators can be used as indicators of disease monitoring, and play an important role in protecting the health of pregnant women with GDM.

Objective:To investigate the risk factors of diabetes mellitus complicated by pulmonary tuberculosis.Methods:The clinical data of 83 patients with diabetes mellitus complicated by pulmonary tuberculosis who received treatment in Taiyuan Fourth People's Hospital from March 2020 to March 2022 were collected. These patients were divided into sensitive group ( n = 45) and resistant group ( n = 38 ) according to the results of drug sensitivity test. Univariate and multivariate non-conditional logistic regression was performed to analyze the influential factors of drug resistance. Results:Univariate logistic regression results revealed that there were significant differences in blood CD4 +T lymphocyte count ( χ2 = 11.73, P = 0.001) and diabetic complications ( χ2 = 4.94, P = 0.026). Multivariate non-conditional logistic regression analysis was performed taking whether blood CD4 +T lymphocyte count was lower than the average level and whether patients with diabetes mellitus had complications as independent variables, and taking whether drug resistance was a dependent variable. The results showed that the OR (95% CI) value of the decreased blood CD4 +T lymphocyte count was 4.909 (1.926-12.514). It is a risk factor for drug resistance of diabetes mellitus complicated by pulmonary tuberculosis. Conclusion:The decrease of blood CD4 +T lymphocyte count is a risk factor of drug resistance in diabetes mellitus complicated by pulmonary tuberculosis, and it should be intervened early in the clinic.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective:To explore the clinical characteristics and treatment outcomes of different types of peritoneal dialysis-associated peritonitis (PDAP).Methods:The clinical data of PDAP patients admitted to the Second Hospital of Jilin University, Second Part of the First Hospital of Jilin University, Jilin Central Hospital and Jilin First Automobile Work General Hospital in Jilin province from 2013 to 2019 were reviewed. According to the type of PDAP, the patients were divided into relapsing group, recurrent group, repeat group and control group, and the baseline data, pathogens culture and treatment outcomes among the four groups were compared.Results:A total of 542 patients with PDAP were enrolled in the study, including 43 cases in relapsing group, 32 cases in recurrent group, 27 cases in repeat group and 440 cases in control group. The median follow-up time was 30.5 (16.0, 50.0) months. The rate of Gram-positive bacteria in repeat group was higher than that of control group (70.37% vs 42.95%, P=0.030); the rate of fungi in recurrence group was higher than that of control group (21.88% vs 3.86%, P=0.006). Compared with control group, relapsing group had a lower cure rate (67.44% vs 83.64%, P=0.048) and a higher relapse rate (23.26% vs 2.27%, P=0.002), and recurrent group had a higher catheter removal rate (28.13% vs 8.18%, P=0.012). Multivariate logistic regression showed that recurrence was an independent risk factor for catheter removal ( OR=5.137, 95% CI 2.105-12.539, P<0.001). The technical failure rates in relapsing group and recurrent group were both higher than those in control group (41.86% vs 17.05%, P=0.002; 46.88% vs 17.05%, P=0.002). Multivariate Cox regression showed that relapse and recurrence were both independent risk factors for technical failure ( HR=2.587, 95% CI 1.525-4.389, P<0.001; HR=3.571, 95% CI 2.022-6.306, P<0.001), and also were independent risk factors for composite endpoint ( HR=1.565, 95% CI 1.045-2.344, P=0.030; HR=2.004, 95% CI 1.269-3.164, P=0.003). Conclusion:Compared with common PDAP, the therapeutic effects and prognosis of relapsing and recurrent PDAP are worse.