ObjectiveTo identify the direct target proteins for the anti-obesity effect of resveratrol （Res） via chemical proteomic analysis and systematically explore the molecular mechanisms by which Res inhibits lipid accumulation in adipocytes from mitochondrial function regulation， adipocyte browning， and inflammation inhibition， thus providing new targets and experimental evidence for the prevention and treatment of obesity and related metabolic diseases. MethodsThe cell counting kit-8 （CCK-8） assay was adopted to detect the safe and effective doses （7.5， 15， 30 μmol·L^-1） of Res for treating 3T3-L1 cells based on the cell survival rate. After being induced to differentiate into mature adipocytes， the cells were assigned into the blank ［treated with dimethyl sulfoxide （DMSO）］ group and the Res （7.5， 15， 30 μmol·L^-1） groups and treated for 48 h. Oil red O staining and total triglyceride （TG） content were assessed to measure lipid accumulation in adipocytes. Target protein identification of Res was conducted through IAA-P-based chemical proteomics combined with high-resolution mass spectrometry. Target proteins of Res were validated by cellular thermal shift assay （CETSA） combined with Western blot analysis. Furthermore， the expression of browning markers peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and mitochondrial uncoupling protein 1 （UCP1）， as well as the target proteins NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8） and high-mobility group protein B1 （HMGB1） were determined by Western blot. The ATP assay kit was used to measure the ATP concentration. Mitochondrial biogenesis was characterized with MitoTracker Green， on the basis of which the regulatory effect of Res on mitochondrial function was analyzed. The level of the inflammatory cytokine tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， on the basis of which the anti-inflammatory effect of Res on adipocytes was evaluated. ResultsCompared with the control group， Res demonstrated safety and efficacy within the range of 7.5-30 μmol·L^-1， without significantly affecting cell viability. Compared with the control group， different concentrations of Res reduced lipid accumulation in 3T3-L1 adipocytes （P<0.01）， promoted the expression of NDUFS8 （P<0.01）， increased the ATP concentration and the protein levels of UCP1 and PGC-1α， elevated the level of TNF-α （P<0.05， P<0.01）. ConclusionNDUFS8 and HMGB1were identified as the target proteins of Res in mitigating obesity. Res promotes mitochondrial biogenesis to induce the browning of 3T3-L1 adipocytes via targeting NDUFS8 and it inhibits the TNF-α-mediated inflammatory signaling via targeting HMGB1， thus inhibiting lipid accumulation and ameliorating obesity.

Objective:To explore the impact of childhood trauma on drug relapse tendency, as well as the mediating role of post-traumatic stress disorder (PTSD).Methods:From March to May 2017, a total of 403 compulsory drug rehabilitation personnel were selected for a cross-sectional study and then were investigated by the general demography scale, drug relapse risk scale, childhood trauma questionnaire (CTQ), and PTSD checklist for DSM-5(PCL-5).SPSS 27.0 software and PROCESS 4.1 macro program were used for correlation analysis, regression analysis and Bootstrap-based mediation analysis.Results:The scores of negative emotions subscale of drug relapse risk scale, emotional abuse and emotional neglect subscales of CTQ had no significant gender differences(all P>0.05).There were gender differences in relapse tendency, childhood trauma, and PTSD total scores as well as other dimensions ( t/ Z=2.08-4.67, all P<0.05).There were pairwise positive correlations among the total score of the drug relapse risk scale(31.68±9.79), CTQ(39.90±12.13), and PCL-5(11(3, 24)) for compulsory isolation and rehabilitation personnel ( r=0.28, 0.36, 0.37, P<0.05).After controlling for gender, childhood trauma could significantly and positively predict drug relapse tendency( β=0.34, t=7.24, P<0.01), and PTSD played a mediating role between childhood trauma and drug relapse tendency, with the indirect effect of 0.11(95% CI=0.06-0.16). Conclusion:Childhood trauma can affect drug relapse tendency directly, and indirectly through PTSD.

Objective:To explore the impact of childhood trauma on drug relapse tendency, as well as the mediating role of post-traumatic stress disorder (PTSD).Methods:From March to May 2017, a total of 403 compulsory drug rehabilitation personnel were selected for a cross-sectional study and then were investigated by the general demography scale, drug relapse risk scale, childhood trauma questionnaire (CTQ), and PTSD checklist for DSM-5(PCL-5).SPSS 27.0 software and PROCESS 4.1 macro program were used for correlation analysis, regression analysis and Bootstrap-based mediation analysis.Results:The scores of negative emotions subscale of drug relapse risk scale, emotional abuse and emotional neglect subscales of CTQ had no significant gender differences(all P>0.05).There were gender differences in relapse tendency, childhood trauma, and PTSD total scores as well as other dimensions ( t/ Z=2.08-4.67, all P<0.05).There were pairwise positive correlations among the total score of the drug relapse risk scale(31.68±9.79), CTQ(39.90±12.13), and PCL-5(11(3, 24)) for compulsory isolation and rehabilitation personnel ( r=0.28, 0.36, 0.37, P<0.05).After controlling for gender, childhood trauma could significantly and positively predict drug relapse tendency( β=0.34, t=7.24, P<0.01), and PTSD played a mediating role between childhood trauma and drug relapse tendency, with the indirect effect of 0.11(95% CI=0.06-0.16). Conclusion:Childhood trauma can affect drug relapse tendency directly, and indirectly through PTSD.

Objective To evaluate the efficacy and safety of combining ureteroscopic holmium laser lithotripsy with microchannel percutaneous nephrolithotomy(mPCNL)in the treatment of upper urinary tract calculus.Methods From September 2020 to September 2023,300 patients diagnosed with upper urinary tract calculus were randomly divided into control group 1,control group 2,and the combined group by random number table method,100 patients in each.Control group 1 received treatment via ureteroscopic holmium laser lithotripsy,control group 2 underwent mPCNL,while the combined group was treated with a combination of ureteroscopic holmium laser lithotripsy and mPCNL.The perioperative indicators,serum inflammatory factor levels,pain scores,and incidence of complications were compared among the three groups.Results The stone clearance rate of the combined group was higher than that of control group 1 and control group 2,the surgical time was longer than that of control group 1 and control group 2,and the hospitalization time was shorter than that of control group 1 and control group 2,but the intraoperative bleeding volume of control group 1 was less than that of combined group and control group 2,the differences were statistically significant(P<0.05).Compared with before surgery,the levels of tumor necrosis factor-α(TNF-α)in three groups was increased 1 h after surgery;Compared with 1 h after surgery,the levels of TNF-α in three groups were decreased at 12 and 24 h after surgery,the differences were statistically significant(P<0.05).The procalcitonin(PCT)levels of the three groups at 1 and 12 h after the operation were significantly higher than those before the operation.The PCT level at 24 h after the operation was significantly lower than that at 12 h after the operation,but significantly higher than that before the operation and 1 h after the operation in three groups,the differences were statistically significant(P<0.05).At 1,12,and 24 h after surgery,the visual analogue scale(VAS)scores of the three groups decreased sequentially,and the control group 1 was lower than that of combined group and control group 1,the difference was statistically significant(P<0.05).The total incidence of complications was no statistically obviously different among the three groups(P>0.05).Conclusion The ureteroscopic holmium laser lithotripsy combined with mPCNL for upper urinary tract calculus has a high stone clearance rate,fast postoperative recovery,and does not increase the incidence of complications.

Objective To evaluate the efficacy and safety of combining ureteroscopic holmium laser lithotripsy with microchannel percutaneous nephrolithotomy(mPCNL)in the treatment of upper urinary tract calculus.Methods From September 2020 to September 2023,300 patients diagnosed with upper urinary tract calculus were randomly divided into control group 1,control group 2,and the combined group by random number table method,100 patients in each.Control group 1 received treatment via ureteroscopic holmium laser lithotripsy,control group 2 underwent mPCNL,while the combined group was treated with a combination of ureteroscopic holmium laser lithotripsy and mPCNL.The perioperative indicators,serum inflammatory factor levels,pain scores,and incidence of complications were compared among the three groups.Results The stone clearance rate of the combined group was higher than that of control group 1 and control group 2,the surgical time was longer than that of control group 1 and control group 2,and the hospitalization time was shorter than that of control group 1 and control group 2,but the intraoperative bleeding volume of control group 1 was less than that of combined group and control group 2,the differences were statistically significant(P<0.05).Compared with before surgery,the levels of tumor necrosis factor-α(TNF-α)in three groups was increased 1 h after surgery;Compared with 1 h after surgery,the levels of TNF-α in three groups were decreased at 12 and 24 h after surgery,the differences were statistically significant(P<0.05).The procalcitonin(PCT)levels of the three groups at 1 and 12 h after the operation were significantly higher than those before the operation.The PCT level at 24 h after the operation was significantly lower than that at 12 h after the operation,but significantly higher than that before the operation and 1 h after the operation in three groups,the differences were statistically significant(P<0.05).At 1,12,and 24 h after surgery,the visual analogue scale(VAS)scores of the three groups decreased sequentially,and the control group 1 was lower than that of combined group and control group 1,the difference was statistically significant(P<0.05).The total incidence of complications was no statistically obviously different among the three groups(P>0.05).Conclusion The ureteroscopic holmium laser lithotripsy combined with mPCNL for upper urinary tract calculus has a high stone clearance rate,fast postoperative recovery,and does not increase the incidence of complications.

Objective To investigate the incidence and risk factors of recurrence of renal calculi after intracavitary lithotripsy. Methods The clinical data of 190 patients with renal stones who underwent endoluminal lithotripsy in our hospital were retrospectively collected. Based on the results of CT, B-ultrasound, or X-ray examination of the urinary system during the 2-year follow-up period, therecurrence of renal calculi was analyzed. Univariate and multivariate Logistic regression were used to analyze the risk factors of stone recurrence. Results of 190 patients, 49 patients experienced stone recurrence within 2 years after surgery, with a recurrence rate of 25.79%. Univariate Logistic regression analysis showed that body mass index(BMI), diabetes, smoking, older age and hypertension were protective factors for stone recurrence. Multivariate Logistic regression analysis showed that diabetes and smoking were risk factors for stone recurrence, while age and hypertension were protective factors for stone recurrence. Conclusion The recurrence of renal stone after intracavitary lithotripsy is common. Diabetes and smoking are risk factors for the recurrence of renal stone, while older age and hypertension are protective factors.

Hepatocellular carcinoma （HCC） is the sixth most common cancer in the world. In recent years， the clinical early diagnosis and treatment protocols of HCC have been improved， whereas the prognosis of patients is still not satisfactory， which is due to the fact that the mechanism of HCC development has not been fully elucidated. Therefore， it is of great significance to explore the molecular mechanisms and key regulatory links of hepatocellular carcinoma development to further improve the diagnosis and treatment of HCC in China. Epigenetics has become a research hotspot because of its reversibility and easy regulation. According to relevant studies， HCC involves the accumulation of multiple genetic and epigenetic changes during the initiation， promotion， and progression stages. HCC is categorized as infantile malnutrition with accumulation， hypochondriac pain， tympan ites， and abdominal mass in traditional Chinese medicine （TCM）. In the treatment of HCC， TCM with low toxicity， multi-targets， and multi-mechanisms can inhibit tumor growth， alleviate the clinical symptoms， and enhance the quality of life of the patients. Chinese medicines and their active ingredients exert anti-HCC effects through epigenetic regulation of DNA methylation， histone modification， and non-coding RNA. Abnormal gene expression due to epigenetic regulation disorders is involved in all stages of HCC development. There are few studies on epigenetic regulation in TCM treatment of HCC， and there is still much room for development in basic and clinical trials. This paper reviews the mechanism of epigenetic regulation in HCC and summarizes the experimental results of TCM research on the related mechanism， with a view to providing a theoretical basis for future research on the mechanism of HCC development and clinical diagnosis and treatment of hepatocellular carcinoma with TCM.

Background: Acute respiratory distress syndrome induced by acute lung injury (ALI) is the main cause for the high mortality of corona-virus disease 2019 (COVID-19). Huashi Baidu formula (HSBD) with the effects of eliminating dampness, clearing heat, ventilating lung, and removing toxin has been proven to be effective in the treatment of COVID-19, especially in severe cases. However, the underlying mechanism and target proteins of HSBD remain unclear. Objective: To provide evidence and decipher the mechanism of HSBD in alleviating inflammation and ALI. Materials and methods: A mouse model of ALI was induced by lipopolysaccharide (LPS), and hematoxylin-eosin staining was used to examine the protective effects of HSBD on the model mice. The cellular thermal shift assay and proteomics analysis were used to predict the target proteins. Furthermore, the A549 cells with peroxiredoxin 5 (PRDX5) knockdown were established to validate the predicted proteins. Results: Huashi Baidu formula treatment mitigated ALI and inflammatory cytokine dysfunction in LPS-induced mice, thus exerting a therapeutic effect on COVID-19. Huashi Baidu formula could serve as a therapeutic agent to alleviate inflammation and lung injury via nuclear factor k B and phosphatidylinositol 3-kinase signaling and interleukin 17 inhibition as well as targeting PRDX5, which could be one of the promising targets for treating inflammation. In the A549 cell line with PRDX5 knockdown (si-PRDX5), the anti-inflammation effects of HSBD, including reversing LPS-induced increase in the nitric oxide level and reduction in the hydrogen peroxide content, were attenuated. Thus, HSBD protected A549 cells from LPS-induced inflammation mainly by targeting PRDX5. Conclusions: Huashi Baidu formula alleviates ALI by targeting nuclear factor κB/phosphatidylinositol 3-kinase and PRDX5, as well as inhibiting the immune response induced by IL-17.

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg^-1·d^-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg^-1·d^-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.