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Volume 32 Issue 10，2026
Original Article
Abstract：Objective: To evaluate the efficacy and safety of Linggui Yangyuan Paste (LG) in treating male infertility caused by asthenozoospermia (AZS) and oligoasthenozoospermia (OAZS) associated with the Chinese medicine (CM) pattern of Shen (Kidney) deficiency and blood stasis. Methods: This randomized, double-blind, double-dummy, parallel-group, multicenter clinical trial enrolled 162 male infertility patients at 5 hospitals in China from June 2023 to February 2024. Using block randomization within strata, participants were assigned (1:1) to LG + Wuzi Yanzong Oral Solution (WZ) placebo or WZ + LG placebo for 12 weeks (each LG 1 sachet and WZ 1 vial, twice daily), with a 12-week follow-up. The primary outcome was the change in total progressive motile sperm count (TPMSC) from baseline to week 12. Secondary outcomes included pregnancy rate, CM symptom score (CMSS), and semen parameters including semen volume (SV), sperm concentration (SC), total sperm count (TSC), progressive motility (PR), and PR+non-progressive motility (NP). Prespecified subgroup analyses on cumulative pregnancy rate and semen parameters were performed for participants with AZS and OAZS. Safety was monitored throughout the trial. Results: Of 162 randomized participants, 145 completed the trial (75 in the LG group and 70 in the WZ group) and were included in the per-protocol analysis. At week 12, the LG group showed significantly greater improvement in TPMSC compared to the WZ group, with an adjusted between-group difference of 8.81×106 sperm (P＜0.05, 95% confidence interval 2.75-14.87). The cumulative pregnancy rate at week 24 was significantly higher in the LG group than the WZ group [24.0% (18/75) vs. 10.0% (7/70), P＜0.05)]. CMSS decreased significantly in both groups, with greater reduction in the LG group (P＜0.05). Subgroup analysis showed that cumulative pregnancy rates were higher in the LG group than in the WZ group in the AZS subgroup at both weeks 12 and 24 (both P＜0.05). In the AZS subgroup analysis, PR and PR+NP showed significantly greater improvements in the LG group (P＜0.05). In the OAZS subgroup, SV, SC, TSC, PR, and PR+NP all showed greater improvements in the LG group (P＜0.05). No adverse events or adverse drug reactions were reported in either group. Conclusions: LG demonstrates significant efficacy and safety in treating male infertility associated with Shen deficiency and blood stasis syndrome, supporting its clinical application as an integrative therapy for male infertility. (Registration No. ITMCTR2023000009)Keywords：male infertility;asthenozoospermia;oligoasthenozoospermia;Linggui Yangyuan Paste;randomized controlled trial;Chinese medicine33|0|0Updated：2026-09-23Original Article
Abstract：Objective: To evaluate the efficacy and safety of Qushi Juanbi Granules (QSJB) combined with Shenling Baizhu Powder (SLBZ) for treating rheumatoid arthritis (RA) patients with low disease activity (LDA) and Pi (Spleen) deficiency and dampness dampness pattern. Methods: This is a single-centre, randomized, double-blind, placebo-controlled clinical trial executed from November 29, 2022 to August 15, 2024. Participants were randomly assigned to the QSJB (with placebo) group or the QSJB+SLBZ group at a ratio of 1:1 using block randomization method. QSJB, SLBZ and placebo were given twice per day for 12 weeks. The primary outcome was the Disease Activity Score-28 with C-reactive protein (DAS28-CRP), assessed both as the between-group difference in DAS28-CRP values and the proportion of patients achieving remission (DAS28-CRP＜2.6). The secondary outcomes included the 28-tender joint count (TJC28), 28-swollen joint count (SJC28), morning stiffness time, resting pain, Health Assessment Questionnaire (HAQ) score, Physician's Global Assessment of Disease Activity (PhGADA) score, Patient's Global Assessment of Disease Activity (PtGADA) score, rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), erythrocyte sedimentation rate (ESR) and CRP. Safety was monitored during the trial. Results: In total, 60 participants were enrolled, 7 dropped out. Fifty-three patients completed the study, with 30 cases in the QSJB+SLBZ group and 23 cases in the QSJB group. Between-group comparisons of DAS28-CRP value at weeks 4 and 12 were not significant (P=0.702, P=0.520). For remission, the week-12 remission rate was numerically higher in the QSJB+SLBZ group than in the QSJB group, without statistical significance (P=0.745). In the QSJB group, both DAS28-CRP and TJC28 were improved after 12 weeks of treatment (P=0.024, P=0.014, respectively), but RF level was elevated at weeks 4 and 12 (both P=0.021). In the QSJB+SLBZ group, DAS28-CRP, TJC28 and SJC28 were improved after 4 weeks (P=0.002, P=0.029 and P=0.001, respectively), TJC28 and SJC28 also improved after 12 weeks (P=0.018, P=0.004, respectively). However, there was no significant difference in DAS28-CRP, anti-CCP, RF, ESR, CRP, TJC28, PhGADA, PtGADA, HAQ, morning stiffness time or resting pain between the two groups (P＞0.05). No significant differences were noted between groups in overall adverse events (AEs) and AE-related discontinuation rates (all P＞0.05). Conclusions: QSJB alone achieved beneficial clinical responses with acceptable tolerability in treating RA patients with LDA and dampness pattern, while QSJB+SLBZ relieved joint pain faster and thus could be a better alternative option. (Trial registration No.ChiCTR2100053894)Keywords：rheumatoid arthritis;low disease activity;Chinese medicine;randomized controlled trial;Shenling Baizhu Powder;Qushi Juanbi Granules6|0|0Updated：2026-09-23Original Article
Abstract：目的本研究旨在通过2型糖尿病（T2DM）相关生殖功能障碍的体内外模型，评估小檗碱（BBR）的干预效果并阐明其潜在作用机制。方法 体内实验中，将适应性喂养后的32只db/db小鼠随机分为模型组、BBR低剂量组、BBR高剂量组及二甲双胍组，每组8只；另以8只BKS小鼠作为正常对照组。各组小鼠连续6周每日灌胃给药（BBR低/高剂量组分别给予150、300mg/kg/d，二甲双胍组给予100mg/kg/d，对照组给予等体积溶媒）。通过HE染色评估卵巢和子宫的形态学变化，包括卵泡分类与计数以及子宫内膜厚度测量。通过口服葡萄糖耐量试验及血清脂质谱（总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇）评估全身代谢水平。利用液相色谱-质谱联用（LC-MS）技术进行血清代谢组学分析以检测激素水平。通过RNA测序解析卵巢与子宫转录组，筛选差异表达基因并开展GO/KEGG富集分析及蛋白质相互作用（PPI）网络分析。关键靶点如水通道蛋白（Aqp）3、5和7通过qPCR和免疫组织化学方法验证。在体外实验中，将KGN细胞暴露于高糖环境（30mmol/L），并分别用BBR（10或25µmol/L）或二甲双胍（12.5或25mmol/L）处理。通过CCK-8法检测细胞活力，免疫荧光技术观察蛋白定位，TUNEL染色检测细胞凋亡，Western blotting分析凋亡标志物及cAMP-PKA通路相关蛋白的表达变化。结果 高剂量BBR显著改善了卵泡发育，恢复糖脂代谢平衡，并调节激素水平。它可调控颗粒细胞中Crhr1与Adrb2的表达，通过cAMP-PKA信号通路抑制细胞凋亡，具体表现为上调Bcl2表达、下调Bax及Caspase-3水平。此外，高剂量BBR可恢复子宫内膜厚度，并上调Aqp3、Aqp5、Aqp7的表达。结论BBR通过调控cAMP-PKA通路及细胞凋亡，有效改善T2DM状态下的卵巢功能与子宫内膜容受性，为T2DM女性生殖功能障碍的治疗提供了潜在候选药物。Keywords：2型糖尿病;生殖障碍;黄连素;中药7|1|0Updated：2026-09-23Original Article
Abstract：Objective: To investigate the effect and underlying mechanism of securinine (Sec) in ovarian cancer (OC) based on network pharmacology, in vivo experiments and proteomics. Methods: ES2 cells were treated with different concentrations of Sec (6.25, 12.5, 25, 50, and 100μmol/L) for 24 h. The cell viability was determined using the MTT assay. ES2 xenograft nude mice were randomly divided into 4 groups (5 mice per group): tumor control, positive control carboplatin (12.5mg/kg), low-dose of Sec (10mg/kg), and high-dose of Sec (20mg/kg). During the treatment period, body weight and tumor volume were monitored. Major organs and tumor tissues were collected for organ index calculation and HE staining. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine were measured using commercial kits. Network pharmacology was used to predict the targets of Sec in OC. The proteomics analysis of tumor tissues was employed to identify key pathways regulated by Sec. The mRNA and protein levels of epidermal growth factor receptor (EGFR), hypoxia-inducible factor alpha (HIF-α), matrix metalloproteinase-9 (MMP9), mechanistic target of rapamycin (mTOR), nuclear factor kappa-B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and the key targets in peroxisome proliferator-activated receptor (PPAR) signaling pathway were determined by qRT-PCR and Western blot, respectively. Molecular docking was used to analyze the interactions between Sec and the core targets. Results: Sec (6.25-100μmol/L) inhibited ES2 cell proliferation (P＜0.05 or P＜0.01). Sec inhibited tumor growth in ES2 xenograft nude mice without toxicity in heart, liver, spleen, lung, and kidneys (P＜0.05 or P＜0.01). Network pharmacology identified 6 core targets associated with Sec's activity: EGFR, HIF-α, MMP9, mTOR, NF-κB, and STAT3. Proteomics analysis revealed PPAR signaling pathway as a key role. qRT-PCR confirmed that Sec significantly inhibited the mRNA levels of mTOR, NF-κB, STAT3, fatty acid-binding protein 3 (FABP3), FABP4, peroxisome proliferator-activated receptor alpha (PPAR-α), and PPAR-δ (P＜0.05 or P＜0.01). Western blot analysis demonstrated that Sec markedly suppressed the expression of FABP3, STAT3, and NF-κB (P＜0.05 or P＜0.01). Molecular docking revealed high binding affinity between Sec and FABP3, FABP4, mTOR, and NF-κB. Conclusion: Sec inhibits OC cell proliferation and tumor growth through the NF-κB and PPAR signaling pathways.Keywords：ovarian cancer;securinine;network pharmacology;proteomics;PPAR signaling pathway8|0|0Updated：2026-09-23Original Article
Abstract：Objective: To study the anti-proliferative and anti-angiogenic mechanism of oridonin in psoriatic keratinocytes by blocking phosphatidylinositol 3-kinase (PI3K/Akt) signaling pathway based on system pharmacology. Methods: Protein targets of oridonin and psoriasis-related genes were predicted and their overlap was determined using the Venny package in R. The DAVID database was used for enrichment analysis. The oridonin-psoriasis-target and oridonin-target-pathway (OTP) networks associated with psoriasis, as well as a protein-protein interaction, were constructed using Cytoscape. Molecular docking with AutoDock was used to verify the relationships between oridonin and core targets, and ZDOCK was used to assess interactions between core proteins. All bioinformatics results were verified empirically. The mRNA levels of core targets in oridonin-treated cells were measured using real-time q-PCR. The HaCaT keratinocytes were divided to 4 groups: control, low-, medium-and high-concentration groups and treated with different concentrations of oridonin (1, 5 and 10μmol/L) for 18 h, and then stimulated with tumor necrosis factor (TNF)-α (20 ng/mL) for 6 h. Western blot was used to detect PI3K/Akt pathway protein levels. Results: Seventy-three targets were found to be strongly associated with the effects of oridonin on psoriasis. The Cluster ONE algorithm was used to extract 6 kernel clusters from the PPI network, and 9 PPI interaction pairs comprising 13 targets showed combined scores 0.999. The OTP network, molecular docking, and protein interaction simulations indicated that oridonin targeted Sirtuin 1 (SIRT1), cyclin dependent kinase 2 (CDK2), Src tyrosine protein kinase (SRC), protein-tyrosine phosphatase, nonreceptor-type (PTPN), and SIRT1-tumor protein p53 (TP53), with the CDK2-TP53, SRC-heat shock protein 90 alpha family class a member 1 (HSP90AA1), and PTPN1-epidermal growth factor receptor (EGFR) interaction pairs regulating the PI3K-Akt signaling pathway. Oridonin was observed to block hyperplasia in HaCaT keratinocytes, accompanied by reduced levels of TNF-α, interleukin (IL-)-6, and IL-1β (P＜0.05 or P＜0.01). qPCR measurements showed that oridonin significantly inhibited the expression of angiogenesis-related genes, including C-X-C chemokine receptor type 7, C-X-C motif chemokine ligand 12, and vascular endothelial growth factor (P＜0.05 or P＜0.01). In addition, the qPCR results showed significant changes in the mRNA levels of SIRT1, CDK2, SRC, PTPN1, TP53, HSP90AA1, and EGFR, and Western blot indicated marked changes in the protein levels of cleaved caspase-3, BAD, Bcl-2, p-ERK1/2, and p-p38 after oridonin treatment (P＜0.05 or P＜0.01). Conclusions: The study identified the primary oridonin targets during psoriasis treatment using network pharmacology. Bioinformatics analysis with empirical verification demonstrated strong associations between SIRT1, CDK2, SRC, PTPN1, TP53, HSP90AA1, and EGFR and oridonin. These interactions were positively correlated with an inhibition of proliferation and angiogenesis mediated by blocking PI3K-Akt signaling pathway.Keywords：oridonin;psoriasis;system pharmacology;keratinocyte proliferation;angiogenesis;PI3K/AKT signaling pathway6|0|0Updated：2026-09-23Original Article
Abstract：Objective: To elucidate the anti-rheumatoid arthritis (RA) mechanisms of Notopterygium incisum essential oil (NIEO) using an integrated strategy combining chemical profiling, network pharmacology, multi-omics data mining, and advanced machine learning, while developing an optimized nanoemulsion (NE) delivery system to enhance its therapeutic applicability. Methods: Gas chromatography-mass spectrometry was employed for chemical profiling of NIEO. Multi-omics integration and machine learning models were used to identify core therapeutic targets, with diagnostic potential assessed via receiver operating characteristic analysis. Computational modeling, including molecular docking and dynamics simulations, provided structural insights into NIEO components interacting with targets. An optimized NIEO-NE was developed and characterized for physicochemical properties [mean diameter, polydispersity index (PDI), encapsulation efficiency]. In vitro assays evaluated NIEO-NE effects on lipopolysaccharide-induced Caspase-1 (CASP1) expression, reactive oxygen species (ROS) production, and pro-inflammatory mediators including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, nitric oxide (NO) in RAW264.7 macrophages. Results:GC-MS identified a-terpineol as the predominant constituent among 17 primary volatile compounds in NIEO. CASP1 was identified as the core target, with an area under curve of 0.985 for RA diagnosis. Molecular docking and dynamics revealed strong interactions between key NIEO components and CASP1's active site. The optimized NIEO-NE exhibited a mean diameter of 82.3nm, PDI of 0.12, and encapsulation efficiency of 94.8%. In vitro, NIEO-NE significantly suppressed LPS-induced CASP1 expression, ROS production, and release of IL-6, TNF-α, IL-1β, and NO (P＜0.01). Conclusions: NIEO exerts anti-RA effects by downregulating CASP1 and modulating the inflammasome pathway, validated through multi-omics and functional assays. The NE formulation overcomes bioavailability limitations, providing a framework for natural product-based drug discovery and positioning NIEO as a promising therapeutic candidate for RA.Keywords：rheumatoid arthritis;Notopterygium incisum essential oil;machine learning;nanoemulsion;caspase-1;network pharmacology7|0|0Updated：2026-09-23
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