ObjectiveTo investigate whether there are differences in the efficacy of Gegen Qinliantang with different contents of Puerariae Lobatae Radix on the acute enteritis （AE） model mice and provide a scientific basis for the interpretation of Gegen Qinliantang in the treatment of "Xie Re Li". MethodsA total of 112 male BALB/c mice were randomly divided into a blank group，model group，single Puerariae Lobatae Radix group，non-Puerariae Lobatae Radix group，regular dose Gegen Qinliantang group （regular dose group），half-dose Puerariae Lobatae Radix group，and doubled-dose Puerariae Lobatae Radix group， with 16 mice in each group. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of the colon tissue. Western blot was employed to detect the expression of ZO-1 （a protein in the tight junction） and Occludin in the colon tissue， as well as the changes of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. ResultsCompared with the blank group，the DAI scores of the mice in the model group were significantly higher （P<0.05），and the histopathological sections of their colon tissues showed mucosal damage，glandular atrophy，disordered arrangement，and a large number of inflammatory cells infiltration，and the expression of ZO-1 and Occludin proteins in their colon tissues was significantly down-regulated （P<0.05，P<0.01）. The expression of inflammatory factors TNF-α and IL-1β was significantly up-regulated （P<0.05，P<0.01）. Compared with the model group，the DAI scores of mice in all dosing groups decreased significantly （P<0.05），with the most significant effect in the regular dose group. After 7 d of drug administration，the regular dose group had the best impact on the repair of colonic mucosa in the AE mouse model. The regular dose group significantly down-regulated the expression of TNF-α （P<0.05） and significantly up-regulated the expression of ZO-1 protein （P<0.05）. The doubled-dose Puerariae Lobatae Radix group significantly down-regulated the expression of IL-1β protein （P<0.01），and there was no significant difference between all dosing groups and the model group in terms of the expression of Occludin protein. After 14 d of drug administration，the best effect on the repair of colonic mucosa in the AE mouse model was observed in the doubled dose Puerariae Lobatae Radix group. All groups except the non-Puerariae Lobatae Radix group significantly down-regulated the expression of TNF-α （P<0.01）. Meanwhile，the regular dose group and doubled-dose Puerariae Lobatae Radix group significantly elevated the expression level of Occludin protein （P<0.01）. The doubled-dose Puerariae Lobatae Radix group also significantly inhibited the expression of IL-1β protein （P<0.05） and up-regulated ZO-1 protein expression （P<0.05）. ConclusionGegen Qinliantang can reduce the pathological damage of colon tissue， protect the barrier function and structure of intestinal epithelial cells， and reduce the expression of inflammatory factors， so as to achieve the therapeutic effect of AE model mice. When comparing the therapeutic efficacy of Gegen Qinliantang containing different Gegen contents， Gegen Qinliantang with the proportion of the original formula of Zhongjing was the most effective in AE model mice.

ObjectiveTo investigate whether there are differences in the efficacy of Gegen Qinliantang with different contents of Puerariae Lobatae Radix on the acute enteritis （AE） model mice and provide a scientific basis for the interpretation of Gegen Qinliantang in the treatment of "Xie Re Li". MethodsA total of 112 male BALB/c mice were randomly divided into a blank group，model group，single Puerariae Lobatae Radix group，non-Puerariae Lobatae Radix group，regular dose Gegen Qinliantang group （regular dose group），half-dose Puerariae Lobatae Radix group，and doubled-dose Puerariae Lobatae Radix group， with 16 mice in each group. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of the colon tissue. Western blot was employed to detect the expression of ZO-1 （a protein in the tight junction） and Occludin in the colon tissue， as well as the changes of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. ResultsCompared with the blank group，the DAI scores of the mice in the model group were significantly higher （P<0.05），and the histopathological sections of their colon tissues showed mucosal damage，glandular atrophy，disordered arrangement，and a large number of inflammatory cells infiltration，and the expression of ZO-1 and Occludin proteins in their colon tissues was significantly down-regulated （P<0.05，P<0.01）. The expression of inflammatory factors TNF-α and IL-1β was significantly up-regulated （P<0.05，P<0.01）. Compared with the model group，the DAI scores of mice in all dosing groups decreased significantly （P<0.05），with the most significant effect in the regular dose group. After 7 d of drug administration，the regular dose group had the best impact on the repair of colonic mucosa in the AE mouse model. The regular dose group significantly down-regulated the expression of TNF-α （P<0.05） and significantly up-regulated the expression of ZO-1 protein （P<0.05）. The doubled-dose Puerariae Lobatae Radix group significantly down-regulated the expression of IL-1β protein （P<0.01），and there was no significant difference between all dosing groups and the model group in terms of the expression of Occludin protein. After 14 d of drug administration，the best effect on the repair of colonic mucosa in the AE mouse model was observed in the doubled dose Puerariae Lobatae Radix group. All groups except the non-Puerariae Lobatae Radix group significantly down-regulated the expression of TNF-α （P<0.01）. Meanwhile，the regular dose group and doubled-dose Puerariae Lobatae Radix group significantly elevated the expression level of Occludin protein （P<0.01）. The doubled-dose Puerariae Lobatae Radix group also significantly inhibited the expression of IL-1β protein （P<0.05） and up-regulated ZO-1 protein expression （P<0.05）. ConclusionGegen Qinliantang can reduce the pathological damage of colon tissue， protect the barrier function and structure of intestinal epithelial cells， and reduce the expression of inflammatory factors， so as to achieve the therapeutic effect of AE model mice. When comparing the therapeutic efficacy of Gegen Qinliantang containing different Gegen contents， Gegen Qinliantang with the proportion of the original formula of Zhongjing was the most effective in AE model mice.

BACKGROUND: The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation. METHODS: A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs). RESULTS: Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs . chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone. CONCLUSIONS ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Nasopharyngeal Carcinoma/drug therapy* ; Nasopharyngeal Neoplasms/drug therapy* ; Neoplasm Recurrence, Local/drug therapy*

This study investigated the functions and regulatory mechanism of Portulacae Herba and its chemical components on the Toll-like receptor 4(TLR4)/myeloid differentiation primary response 88(MyD88)/nuclear factor kappa B(NF-κB) inflammatory signaling pathway in the colon tissue of mice with dextran sodium sulfate(DSS)-induced ulcerative colitis(UC). A total of 35 mice were randomly divided into groups, including a blank group, a model group, a mesalazine group(0. 5 g·kg~(-1)), and low, medium,and high dose alkaloids from Portulacae Herba groups(9, 18, 36 mg·kg~(-1)), and a combination treatment group, with 5 mice in each group. The blank group was given purified water, while the other groups were continuously given a 3% DSS solution for 7 days to induce the UC model. From day 8 onwards, the treatment group received oral gavage according to the prescribed doses for 14 days. The overall condition, body weight, stool characteristics, and presence of blood in the stool were recorded daily. After the experiment, the disease activity index(DAI) was assessed for each group, and colon length was measured. Histopathological changes in colon tissue were examined using hematoxylin-eosin(HE) staining. The levels of pro-inflammatory cytokines, tumor necrosis factor-α(TNF-α),and interleukin-1β( IL-1β) in serum were measured by enzyme-linked immunosorbent assay( ELISA). The protein and m RNA expression of TLR4, MyD88, and NF-κB in colon tissue were measured using Western blot and quantitative real-time PCR(qPCR).Compared to the blank group, the model group showed a significant decrease in body weight, a notable increase in DAI scores, a significant shortening of colon length, and evident histopathological damage. The levels of inflammatory cytokines TNF-α and IL-1β in the serum were significantly elevated, and the protein and m RNA expression of TLR4, MyD88, and NF-κB in colon tissue were significantly up-regulated. In contrast, the alkaloids from Portulacae Herba treatment groups significantly improved symptoms and reduced body weight loss in mice, decreased DAI scores, alleviated colon shortening, lowered serum levels of TNF-α and IL-1β,significantly down-regulated the expression levels of TLR4, MyD88, and NF-κB proteins and genes in colon tissue, as well as reduced histopathological damage. Therefore, the study suggests that alkaloids from Portulacae Herba can alleviate intestinal inflammation damage in DSS-induced UC mice, with its mechanism involving the TLR4/MyD88/NF-κB signaling pathway.
Animals ; Colitis, Ulcerative/immunology* ; Toll-Like Receptor 4/immunology* ; Myeloid Differentiation Factor 88/metabolism* ; Mice ; NF-kappa B/metabolism* ; Signal Transduction/drug effects* ; Male ; Alkaloids/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Female ; Colon/metabolism* ; Disease Models, Animal

Utilizing network pharmacology, molecular docking, and cellular experimental validation, this study delved into the therapeutic efficacy and underlying mechanisms of matrine in combating senescence. Databases were utilized to predict targets related to the anti-senescence effects of matrine, resulting in the identification of 81 intersecting targets for matrine in the treatment of senescence. A protein-protein interaction(PPI) network was constructed, and key targets were screened based on degree values. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on the key targets to elucidate the critical pathways involved in the anti-senescence effects of matrine. Molecular docking was conducted between matrine and key targets. A senescence model was established using human umbilical vein endothelial cells(HUVECs) induced with hydrogen peroxide(H_2O_2). Following treatment with varying concentrations of matrine(0.5, 1, and 2 mmol·L~(-1)), cell viability was assessed by using the CCK-8. SA-β-galactosidase staining was employed to observe the positive rate of senescent cells. Flow cytometry was utilized to measure the apoptosis rate. Real-time quantitative PCR(RT-PCR) was utilized to measure the mRNA expression of apoptosis-related cysteine peptidase 3(CASP3), albumin(ALB), glycogen synthase kinase 3β(GSK3B), CD44 molecule(CD44), and tumor necrosis factor-α(TNF-α). Western blot was performed to detect the protein expression of tumor protein p53(p53), cyclin-dependent kinase inhibitor 1A(p21), cyclin-dependent kinase inhibitor 2A(p16), and retinoblastoma tumor suppressor protein(pRb) in the senescence signaling pathway, p38 protein kinase(p38), c-Jun N-terminal kinase(JNK), and extracellular regulated protein kinases(ERK) in the mitogen-activated protein kinase(MAPK) pathway, and phosphatidylinositol 3-kinase(PI3K) and protein kinase B(Akt) in the PI3K/Akt signaling pathway. The experimental results revealed that matrine significantly increased the viability of HUVECs(P<0.05), decreased the positive rate of senescent cells and the apoptosis rate(P<0.05), and reduced the mRNA expression levels of CASP3, ALB, GSK3B, CD44, and TNF-α(P<0.05). It also inhibited the protein expression of p53, p21, p16 and pRb in the senescence signaling pathway(P<0.05), upregulated the protein expression of p-PI3K/PI3K and p-Akt/Akt(P<0.05), and downregulated the protein expression of p-p38/p38, p-JNK/JNK, and p-ERK/ERK(P<0.05). Collectively, these findings suggest that matrine exerts an inhibitory effect on HUVECs senescence, and its mechanism involves the modulation of the senescence signaling pathway, MAPK pathway, and PI3K/Akt signaling pathway to suppress cell apoptosis and inflammation.
Humans ; Matrines ; Quinolizines/chemistry* ; Alkaloids/chemistry* ; Human Umbilical Vein Endothelial Cells/cytology* ; Cellular Senescence/drug effects* ; Network Pharmacology ; Molecular Docking Simulation ; Signal Transduction/drug effects* ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Traditional Chinese medicine(TCM) is the pillar for the development of motherland medicine, and animal medicine has a long history of application in China, characterized by wide resources, strong activity, definite efficacy, and great benefits. It has significant potential and important status in the consumption market of raw materials of TCM. In the context of global climate change, farming system alterations, and low renewability, the depletion of wild medicinal animal resources has accelerated. Accordingly, the conservation and sustainable utilization of wild resources of animal medicinal materials has become a problem that garners increasing attention and urgently needs to be solved. This paper summarizes the current situation of domestic and foreign medicinal animal breeding and research progress in industrial application in recent years and points out the issues related to standardized breeding, germplasm selection and breeding, and quality evaluation standards for medicinal animals. Furthermore, this paper discusses standardized breeding, quality standards, resource protection and utilization, and the search for alternative resources for rare and endangered medicinal animals. It proposes that researchers should systematically carry out in-depth basic research on animal medicine, improve the breeding scale and level of medicinal animals, employ modern technology to enhance the quality standards of medicinal materials, and strengthen the research and development of alternative resources. This approach aims to effectively address the relationship between protection and utilization and make a significant contribution to the sustainable development of medicinal animal resources and the animal-based Chinese medicinal material industry.
Animals ; Breeding ; China ; Medicine, Chinese Traditional ; Conservation of Natural Resources

Panax ginseng as a perennial herb of Araliaceae, exhibits pharmacological effects such as central nervous system stimulation, anti-tumor properties, and cardiovascular and cerebrovascular protection. The B3 gene family plays a crucial role in growth and development, antioxidant activity, stress resistance, and secondary metabolism regulation of plants and has been extensively studied in various plants. However, the identification and analysis of the B3 gene family in P. ginseng have not been reported. In this study, a total of 145 B3 genes(PgB3s) with complete open reading frames(ORF) were identified from P. ginseng and classified into five subfamilies based on domain types. Through correlation analysis with ginsenoside content, SNP/InDels analysis, and interaction analysis with key enzyme genes, 15 PgB3 transcripts were found to be significantly correlated with ginsenoside content and exhibited a close interaction network with key enzyme genes involved in ginsenoside biosynthesis, which indicated that these genes may participate in the regulation of ginsenoside biosynthesis. Additionally, this study found that PgB3 genes exhibited induced expression in response to methyl jasmonate(MeJA) stress, which aligned with the presence of abundant stress response elements in their promoters, confirming the important role of the B3 gene family in P. ginseng in stress resistance. The results of this study revealed the potential functions of PgB3 genes in ginsenoside biosynthesis and stress response, providing a significant theoretical basis for further research on the functions of PgB3 genes and their regulatory mechanisms.
Panax/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Ginsenosides/biosynthesis* ; Multigene Family ; Phylogeny

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Nigella sativa L. seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo. This study revealed that the ethanolic extract of Nigella sativa L. (HZC) enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes. In accordance with established protocols, the ethanol fraction from Nigella sativa L. seeds was extracted, concentrated, and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, tyrosinase activity evaluation, measurement of cellular melanin contents, scratch assays, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis for expression profiling of experimentally relevant proteins. The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr, Mitf, and gp100 in B16F10 cells. Furthermore, HZC effectively mitigated oxidative stress-induced cellular senescence, improved melanocyte condition, and rectified various functional impairments associated with melanocyte dysfunction. These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK, PKA, and Wnt signaling pathways. In addition, HZC attenuates oxidative damage induced by H₂O₂ therapy by activating the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and enhancing the activity of downstream antioxidant enzymes, thus preventing premature senescence and dysfunction in melanocytes.
Oxidative Stress/drug effects* ; Melanocytes/cytology* ; Cellular Senescence/drug effects* ; Nigella sativa/chemistry* ; Plant Extracts/pharmacology* ; Seeds/chemistry* ; Mice ; Animals ; Melanins/metabolism* ; Monophenol Monooxygenase/metabolism* ; Humans