Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

This study aims to understand the epidemic distribution characteristics,antimicrobial resistance,virulence genes,and biofilm adhesion ability of Enterococcus in yaks on the Tibetan plateau.Three hundred and forty-six fresh yak fecal samples and 311 milk samples were collected from four provinces on the Tibetan plateau(Xizang,Sichuan,Gansu,Qinghai),totaling 657 sam-ples.Bacterial isolation and identification were conducted,followed by 16S rDNA gene detection and the construction of a systematic evolutionary tree.The isolated strains were tested for antimi-crobial resistance and virulence genes using PCR,and sensitivity tests were performed using 18 types of antibiotics.The biofilm adhesion ability of the isolated bacteria was determined using an improved semi-quantitative crystal violet staining method.The results showed that the total isola-tion rate of Enterococcus was 32.27％,with Sichuan having the highest at 60.23％,followed by Gansu,Qinghai,and Tibet autonomous region at 42.70％,23.47％,and 18.31％respectively.In terms of sample types,the isolation rate in fecal samples was 36.71％,and in milk samples,it was 27.33％.Through PCR amplification,bands of approximately 1 400 bp were obtained,and 5 strains were selected for evolutionary analysis,forming a separate cluster.Among the 212 isolated strains,a high resistance to clindamycin,quinupristin-dalfopristin,linezolid,levofloxacin,and erythromycin was observed,with various resistance phenomena,accounting for 60.85％.Only 5 out of 12 resist-ant genes were detected,namely erm(B),tet(L),tet(O),tet(M),and ant(6)-Ia.All 13 virulence genes were detected in Enterococcus,with detection rates in the range of 5.19％to 95.76％,where cpd was 95.75％,gelE was 91.98％,efaA was 86.79％,asal was 86.32％,and the rest ranged from 5.19％to 55.66％.The fsr virulence gene was not detected in Enterococcus from milk sources.Among the isolated strains,3.30％showed medium adhesive ability,48.58％showed weak adhesive ability,and 48.11％showed no adhesive ability.The above research revealed the preva-lence of yak derived Enterococcus,the carrying status of resistance and virulence genes,and the correlation between biofilm phenotypes,laying the foundation for mastering research data on yak-derived Enterococcus in the Tibetan plateau.

This study aims to understand the epidemic distribution characteristics,antimicrobial resistance,virulence genes,and biofilm adhesion ability of Enterococcus in yaks on the Tibetan plateau.Three hundred and forty-six fresh yak fecal samples and 311 milk samples were collected from four provinces on the Tibetan plateau(Xizang,Sichuan,Gansu,Qinghai),totaling 657 sam-ples.Bacterial isolation and identification were conducted,followed by 16S rDNA gene detection and the construction of a systematic evolutionary tree.The isolated strains were tested for antimi-crobial resistance and virulence genes using PCR,and sensitivity tests were performed using 18 types of antibiotics.The biofilm adhesion ability of the isolated bacteria was determined using an improved semi-quantitative crystal violet staining method.The results showed that the total isola-tion rate of Enterococcus was 32.27％,with Sichuan having the highest at 60.23％,followed by Gansu,Qinghai,and Tibet autonomous region at 42.70％,23.47％,and 18.31％respectively.In terms of sample types,the isolation rate in fecal samples was 36.71％,and in milk samples,it was 27.33％.Through PCR amplification,bands of approximately 1 400 bp were obtained,and 5 strains were selected for evolutionary analysis,forming a separate cluster.Among the 212 isolated strains,a high resistance to clindamycin,quinupristin-dalfopristin,linezolid,levofloxacin,and erythromycin was observed,with various resistance phenomena,accounting for 60.85％.Only 5 out of 12 resist-ant genes were detected,namely erm(B),tet(L),tet(O),tet(M),and ant(6)-Ia.All 13 virulence genes were detected in Enterococcus,with detection rates in the range of 5.19％to 95.76％,where cpd was 95.75％,gelE was 91.98％,efaA was 86.79％,asal was 86.32％,and the rest ranged from 5.19％to 55.66％.The fsr virulence gene was not detected in Enterococcus from milk sources.Among the isolated strains,3.30％showed medium adhesive ability,48.58％showed weak adhesive ability,and 48.11％showed no adhesive ability.The above research revealed the preva-lence of yak derived Enterococcus,the carrying status of resistance and virulence genes,and the correlation between biofilm phenotypes,laying the foundation for mastering research data on yak-derived Enterococcus in the Tibetan plateau.

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.
Male ; Female ; Humans ; Adult ; Retrospective Studies ; Treatment Outcome ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Precursor Cells, T-Lymphoid ; Leukemia, Myeloid, Acute/drug therapy*

Humans ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Hydrazines/therapeutic use* ; Leukemia, Myeloid, Acute/drug therapy*

Antigens, CD19 ; Child ; Humans ; Immunotherapy, Adoptive ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; T-Lymphocytes

The teaching effect of "process management and evaluation" was assessed in resident standardization training plan in acupuncture-moxibustion department of hospital for postgraduates of non-acupuncture-moxibustion speciality. A total of 120 postgraduates of non-acupuncture-moxibustion speciality participating in resident standardization training were randomized into an observation group (60 cases) and a control group (60 cases, 1 case dropped off). In the control group, the conventional training mode was used. In the observation group, the "process management and evaluation" was adopted, in which, the syllabus was refined, various teaching modes were cooperated and the summary was conducted once a week. The training results were evaluated at the end of 1-month shift test and questionnaire was issued in all of the postgraduates of the two groups. In the observation group, the score for theory and the score of each of the items for technical ability, named differentiation and treatment, technical manipulation and physician-patient communication, as well as the total score were all higher than the control group successively (
Acupuncture ; Acupuncture Therapy ; Hospitals ; Humans ; Moxibustion ; Reference Standards

Objective:To construct oxaliplatin (L-OHP) drug-resistant cell line HCT-116/L-OHP in human colon cancer, in order to observe the reversal effect of curcumin (cur) on its drug resistance, and preliminarily explore the possible drug resistance mechanism. Method:The concentration gradient increasing method was used to gradually increase the L-OHP concentration of HCT-116 in parental colon cancer cells, and the cell line HCT-116/L-OHP resistant to L-OHP was established. The cytotoxicity of L-OHP and curcumin to HCT-116 and HCT-116/L-OHP cells was detected by cell counting kit-8(CCK-8) method to observe whether curative resistance could be reversed. Western blot was used to detect the expressions of drug-resistance-related proteins. Real-time PCR was used to detect changes in related genes. Result:Human colon cancer cell line resistant to L-OHP were successfully established and named as HCT-116/L-OHP, with a drug resistance index of 12.6.Compared with HCT-116 cell lines, the expression levels of resected and repaired cross complementation gene 1 (ERCC1) protein and gene in HCT-116/L-OHP cell lines were significantly increased (P<0.01). The expressions of B-cell lymphoma-2 (Bcl-2), glutathione-s-transferase-consciousness (GST-consciousness), multidrug resistance-associated protein (MRP), P-glycoprotein (P-gp) and apoptotic inhibitory gene (Survivin) also increased significantly (P<0.01). After the treatment with different concentrations of curcumin (5,10,20,30,40 μmol·L^-1), the expression of ERCC1 decreased (P<0.01), and the expressions of Bcl-2,GST-π,MRP,P-gp,Survivin also decreased to different degrees (P<0.05). Conclusion:HCT-116/L-OHP cell lines have a stable drug resistance, and its drug resistance mechanism may be up-regulated with the expression of ERCC1, which leads to the up-regulation of Bcl-2,GST-π,MRP,P-gp,Survivin and other related proteins, and enables tumor cells to acquire drug resistance. Curcumin can reverse the drug resistance of HCT-116/L-OHP, and its mechanism may be to reduce the expression of ERCC1, thereby down-regulating the expressions of Bcl-2,GST-π,MRP,P-gp,Survivin and other drug-resistant related genes and proteins, and increase the sensitivity of tumor to L-OHP, so as to reverse the drug resistance of tumor cells.

Aim To clarify the role of autophagy in the regulation mechanism of epithelial-mesenchymal transition(EMT) in hepatocytes and the transition to myofibroblast. Methods BNL CL. 2, a mouse embryonic hepatocyte, and BNL CL. 2 cells knocked-down BECN1 genes were treated with TGF-β1(2 μg . L-1) and curcumin(10, 20, 30 jimol • L - 1 ) . Real-time PCR and Western blot were used to detect Beclin-1, LC3, Vimentin and α-SMA gene and protein expression in BNL cl. 2 cells. The optical microscope was used to observe the changes of cell morphology. And the changes in cell autophagy were detected by GFPLC3 plasmid transfection. Results After the intervention of TGF-β1, the expression of Vimentin and α-SMA, the mesenchymal marker, increased and the autophagy decreased. Curcumin could inhibit Vimentin and a-SMA expression in hepatocytes. Moreover, curcumin could increase the autophagy related genes and protein expression of Beclin-1 and LC3 in hepatocytes. Curcumin could increase the level of autophagy and inhibit the cell transformation to myofibroblast-like cells. After interfering with BECN1, the effect of curcumin inhibiting hepatic EMT was partially blocked. Conclusions Curcumin could inhibit the process of EMT of hepatocytes by increasing the level of autophagy. The occurrence and development of liver fibrosis was consequently inhibited.