Polygonatum sibiricum， as a traditional Chinese medicine with both medicinal and edible properties， has attracted considerable attention due to its functions of nourishing Yin and moistening the lungs， tonifying the spleen and benefiting Qi， and nourishing the kidneys and filling essence. Recent studies have demonstrated that Polygonatum sibiricum plays a significant role in regulating the immune system， effectively enhancing and improving the morphology and function of immune organs， stimulating the proliferation and activation of immune cells， and regulating the secretion and release of immune factors， thereby enhancing the immune function of the body and improving various immune-related diseases. Although a large number of studies have explored the pharmacological effects and mechanisms of P. sibiricum， there has been no systematic review and summary of its immune regulatory activity and mechanisms. Therefore， this article comprehensively reviews the research achievements of P. sibiricum polysaccharides and saponins in the field of immune regulation in recent years， and further sorts out the immune regulatory mechanisms of P. sibiricum in multiple aspects： including increasing the organ index of the spleen and thymus， increasing the number and activity of tumor-suppressive bone marrow hematopoietic stem cells， improving intestinal flora imbalance， regulating the quantity and proportion of T lymphocyte subsets， increasing the level of immunoglobulin， promoting the proliferation of macrophages， enhancing the activity of natural killer cells， increasing the number of white blood cells， and promoting the maturation of dendritic cells， providing a solid theoretical basis and scientific evidence for the research and application of P. sibiricum， and promoting its development and application in traditional Chinese medicine immune enhancers and various functional products.

OBJECTIVE: To observe the clinical efficacy and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping. METHODS: A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety. RESULTS: All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001). CONCLUSION Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.
Humans ; Female ; Male ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae/physiopathology* ; Cupping Therapy/methods* ; Pressure ; Aged ; Treatment Outcome

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective:This study aims to evaluate the impact of Diagnosis-Related-Groups(DRGs)payment on the average total cost,length of stay,service volume,effectiveness,and characteristics of traditional Chinese medicine(TCM)hospitals.Methods:A national medical center specializing in TCM was selected as the research subject.The Difference-in-Difference Model(DID)was utilized to analyze the differences in various indicators between insured patients(intervention group)and uninsured patients(control group)before and after the implementation of the payment reform policy.The reliability and stability of the model were verified through parallel trend tests and placebo tests.Results:The coefficients of DID interaction terms for eleven indicators including average total hospitalization cost,number of cases,length of stay,proportion of medical service revenue,and proportion of herbal medicine revenue were significant(P<0.05).The DID interaction term coefficients for four indicators including herbal medicine usage rate and proportion of non-pharmacological TCM therapy revenue were not significant(P>0.05).Conclusion:DRG payment significantly reduced the per-admission cost,with significant decreases in consumables and medical technology expenses,optimizing cost structure,and a slight decrease in the proportion of herbal medicine costs.It is necessary to further expand the sample size,track policy impacts,and comprehensively evaluate the effects of DRG payment on TCM hospitals in China.

Objective To study the effects of hesperidin on the migration ability of human keratinocytes(HaCaT)and human skin fibroblasts(HSF).Additionally,this research aims to preliminary investigate the influence and underlying mechanism of Hesperidin in facilitating the healing process of acute skin wounds in mice.Methods HaCaT and HSF were divided into blank group(without any treatment),control group(added 0.1％dimethyl sulfoxide)and experimental group(added 5.0 μg·mL-1 hesperidin)for 48 h.The healing ability of cells in vitro was detected by scratch test.The migration of cells was detected by Transwell migration test.C57 mice were randomly divided into model group,experimental-L,-H groups.The acute full-thickness skin defect wound model was established by surgical clipping of the full-thickness skin of the back of mice.The model group was given 0.5％dimethyl sulfoxide,and the experimental-L,-H groups were given 10,50 mg·kg-1 hesperidin solution,respectively.The protein expressions levels of β-catenin,proliferating cell nuclear antigen(PCNA),keratin 14 and collagen Ⅰ were detected by Western blot.Results The scratch healing rates of HaCaT-blank group,HaCaT-control group and HaCaT-experimental group were(21.05±1.10)％,(22.33±1.72)％and(41.61±2.90)％;the cell migration numbers were 57.00±11.36,60.38±10.11 and 287.75±20.21,respectively.The scratch healing rates of HSF-blank group,HSF-control group and HSF-experimental group were(17.82±1.62)％,(19.81±3.87)％and(64.22±1.94)％,the cell migration numbers were 43.25±7.98,40.75±6.70 and 140.88±14.35,respectively.The HaCaT-experimental group was compared with HaCaT-blank group and HaCaT-control group,and the HSF-experimental group was compared with HSF-blank group and HSF-control group,the differences were statistically significant(all P＜0.05).The protein expression levels of β-catenin in the model group,experimental-L,-H groups were 0.53±0.06,0.74±0.17 and 1.44±0.11;the protein expression levels of keratin 14 were 0.33±0.06,0.54±0.07 and 1.26±0.16;the protein expression levels of PCNA were 0.46±0.05,0.72±0.09 and 1.14±0.11;the protein levels of collagen Ⅰ were 0.52±0.03,0.77±0.05 and 1.28±0.13,respectively.There were significant differences in the above indexes between the experimental-L,-H groups and the model group(P＜0.05,P＜0.01).Conclusion Hesperidin may promote the healing of acute skin wounds in mice by activating the Wnt/β-catenin signaling pathway and increasing the migration of HaCaT and HSF.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

BACKGROUND: Previous studies have extensively investigated traditional predictors of cardiovascular disease (CVD) development, progression, and prognosis. However, the influence of novel indicators such as Klotho, on CVD prevalence and prognosis in the general population remains unclear. METHOD: This was an observational study that utilized cross-sectional and longitudinal methods to examine the general population in the National Health and Nutrition Examination Survey (NHANES) 2007-2016. The participants were divided into four groups according to the Klotho quartiles. Primary outcome was CVD [coronary artery disease (CAD), congestive heart failure, and stroke], secondary outcomes were all-cause mortality and cardiovascular mortality. Survey-weighted binary logistic regression analysis was used to analyze the association between Klotho and the prevalence of primary outcome, and the restricted cubic spline (RCS) curve was used to further analyze the nonlinear relationship. Subgroup analyses were conducted to investigate the association between Klotho values and CVD prevalence using survey-weighted binary logistic regression. The incidence of the secondary outcomes among four groups was assessed through Kaplan-Meier survival analysis. Additionally, the relationship between Klotho values and secondary endpoints was explored using survey-weighted Cox proportional hazards regression across various patient subpopulations. RESULTS: A total of 12,146 participants (56.8 ± 10.7 years, 48.5% male) were included in our study. The total incidence of CVD was 9.9% (n = 1201), of which 4.7% (n = 574) were CAD, 3.7% (n = 454) were congestive heart failure, and 4.1% (n = 497) were stroke. Binary logistics regression analysis showed that higher Klotho quartiles were associated with the decreased prevalence of CVD [Quartile 4 vs. Quartile 1: odds ratio (OR) (95% CI): 0.77 (0.64-0.93), P = 0.006] and congestive heart failure [Quartile 4 vs. Quartile 1: 0.75 (0.56-0.99), P = 0.048], However, no significant associations were found between Klotho levels and the outcomes of CAD or stroke. RCS curve illustrated a high Klotho value was negatively correlated with the prevalence of CVD (nonlinear P = 0.838), congestive heart failure (nonlinear P = 0.110) and stroke (nonlinear P = 0.972). No significant interactions were observed in any subgroups regarding the associations between Klotho and prevalence of CVD. After a median follow-up period of 93 months (range: from 1 to 160 months), there were 1228 cases (10.1%) of all-cause mortality in the general population, including 296 cases (2.4%) of cardiovascular mortality. The Kaplan-Meier curves indicated that lower Klotho levels were associated with a significant increase in all-cause mortality across the general population, CVD population, and non-CVD population. As Klotho levels decreased, there was also a notable rise in cardiovascular mortality in both the general population and the CVD population. In the overall population, Cox regression analyses demonstrated that higher Klotho values were associated with a decreased risk of both all-cause and cardiovascular mortality. And no significant interaction was observed in the CVD subgroup regarding the association between Klotho and mortality. CONCLUSION High Klotho level was associated with low prevalence of CVD and low risk of mortality in general population.

Objective To establish an ultra-high performance liquid chromatography-tandem mass spectrometry for the determination of concentration of zanubrutinib in plasma.Method Multi-reaction ion(MRM)detection in positive mode is adopt in the method.The chromatographic column is ZORBAX Eclipse Plus C]8 column(1.8 μm,2.1 mm × 50.0 mm,I.D.Agilent Corporatio,MA,USA);Mobile phase:0.1％formic acid water and acetonitrile,gradient elution with a flow rate of 0.4 mL·min-1 and a volume of 2 μL was injected into the system.The plasma samples were prepared with acetonitrile for precipitation.After a single dose of 15 mg·kg-1 zanubrutinib for six adult male SD rats,blood was collected from the tail vein.The concentration of zanubrutinib in the rat plasma samples was measured,and the pharmacokinetic parameters were calculated by DAS 3.0.Result The linear range of zanubrutinib was 1-500 ng·mL-1 with good linearity.The intra-day and intra-day precision were less than 15％,and the relative recovery was 95.74％-99.19％.The absolution recovery,matrix effect and stability met the requirements;Pharmacokinetic parameters Cmax was(30.15±81.55)ng·mL-1,tmax was(0.32±0.16)h,t1/2 was(5.05±0.62)h,AUC0-t was(271.55±149.01)ng·h·mL-1.Conclusion The method for the determination of zanubrutinib in plasma established in this study has the characteristics of high sensitivity,rapid detection and good repeatability,and is suitable for the determination of zanubrutinib in plasma and the study of pharmacokinetics of zanubrutinib.

OBJECTIVE: To observe the clinical efficacy of intercondylar fossa plasty in preventing intercondylar fossa impingement syndrome after high tibial osteotomy. METHODS: From August 2018 to August 2020, 84 patients with inverted knee osteoarthritis were treated by arthroscopy combined with high tibial osteotomy, and were divided into two groups with 42 cases in each group according to different surgical methods. In the intercondylar fossa plasty group, there were 13 males and 29 females, age ranged from 52 to 67 years old with an average of(58.27±4.32) years old, and arthroscopic intercondylar fossa plasty was performed first, and then high tibial osteotomy. In the arthroscopic cleansing group, 16 males and 26 females, age ranged from 50 to 71 years old with an average of (59.02±5.14) years old, underwent arthroscopic cleansing and then high tibial osteotomy. Postoperative treatment was evaluated using visual analogue scale(VAS), hospital for special surgery (HSS) score for the knee, and the occurrence of intercondylar percussa impingement. RESULTS: All 84 patients were followed up, the duration ranged from 12 to 18 months with an average of (14.1±1.6) months. The VAS and HSS score of knee joint at 6, 12 and 18 months after surgery were significantly improved compared with preoperative period, and there was no significant difference between the two groups (P>0.05), but the incidence of intercondylar fossa index and intercondylar fossa impact between the two groups was significantly compared 18 months after surgery (P<0.05). CONCLUSION Intercondylar fossa plasty can effectively prevent the incidence of intercondylar fossa impact after high tibial osteotomy, and has a more significant effect on postoperative knee pain and function improvement.
Male ; Female ; Humans ; Middle Aged ; Aged ; Tibia/surgery* ; Osteoarthritis, Knee/surgery* ; Knee Joint/surgery* ; Treatment Outcome ; Osteotomy/methods* ; Pain, Postoperative ; Retrospective Studies