Chinese Journal of Integrative Medicine最新文献

Objective: To investigate the ameliorative effects of quercetin (QE) on spermatogenic function and elucidate the underlying molecular mechanisms in vivo.

Methods: Thirty male C57BL/6 mice (6-8 weeks old) were randomly divided into 5 groups using a random number (n=6 per group): control, triptolide (TP) model (0.1 mg/kg per day), and different doses of quercetin (QE) treatment groups (25, 50, and 100 mg/kg per day, intragastrically). Except for controls, all mice received TP to induce spermatogenic impairment, with concurrent QE administration in treatment groups. The intervention lasted 35 days, covering 1 complete spermatogenic cycle, and mice were euthanized on day 38. Histopathological damage and apoptosis in spermatogenic cells were evaluated using hematoxylin and eosin (H&E) staining, TUNEL assay, and Western blot analysis for Bcl-2, Bax, and cleaved caspase-9. Blood-testis barrier (BTB) integrity was assessed by immunofluorescence and Western blot for tight junction proteins, including zonula occludens-1 (ZO-1) and junctional adhesion molecule A (JAMA). The PI3K/AKT signaling pathway was investigated through Western blot analysis of PI3K, AKT, and phosphorylated AKT (p-AKT). Network pharmacology and molecular docking simulations were performed to predict QE's molecular mechanisms, followed by experimental verification.

Results: QE treatment significantly ameliorated TP-induced testicular damage, increased spermatogenic epithelial thickness and spermatogonial tubule diameter, and decreased apoptosis of spermatogenic cells (P<0.05 or P<0.01). QE also improved the distribution and expression of key BTB proteins, including ZO-1 and JAMA (P<0.05 or P<0.01). Network pharmacology and molecular docking studies suggested that QE influences the PI3K-AKT signaling pathway, which was confirmed by increased AKT phosphorylation levels observed in Western blot results (P<0.05 or P<0.01).

Conclusions: QE can mitigate TP-induced spermatogenic dysfunction, reduce apoptosis of spermatogenic cells, and preserve BTB structural integrity by upregulating the PI3K-AKT signaling pathway. QE may be a potential therapeutic agent for treating TP-induced spermatogenic disorders.

Objective: To develop a core outcome set (COS) specifically tailored for integrative medicine clinical research in spinal metastases (SM), aiming to standardize efficacy evaluation and enhance consistency in outcome reporting across clinical trials.

Methods: This study adhered to the methodological standards outlined in the COMET Handbook 1.0, the Core Outcome Set-Standards for Development (COS-STAD), and the T/CACM 1339-2020 guidelines for the development of core outcome sets in Chinese medicine (CM) clinical trials. Candidate outcomes were initially identified through a systematic literature review and semi-structured stakeholder interviews. These outcomes were subsequently refined through a 2-round Delphi survey process, followed by final consensus at an online meeting. The development of a COS for the integration of traditional Chinese medicine and Western medicine clinical research in SM (COS-TCM-SM).

Results: Following 2 rounds of the Delphi survey involving 62 and 61 stakeholders respectively, 10 outcomes met the inclusion criteria. A final online consensus meeting involving 25 stakeholders finalized the selection and refined 1 outcome domain. The finalized COS-TCM-SM comprises 11 outcomes categorized into 7 domains: survival (overall survival, progression-free survival), neurological function (spinal cord function), pain (pain relief rate), health-related quality of life (self-care ability, activity status, psychological state), radiological outcomes (spinal stability, local tumor control), CM-specific outcome (syndrome differentiation score), and safety events (adverse events and complications).

Conclusions: The COS-TCM-SM provides a consensus-based framework that standardizes outcome measurement for integrative medicine clinical research in SM. By integrating key indicators from both CM (syndrome differentiation) and Western medicine (survival, radiological outcomes), it directly addresses the critical issue of outcome heterogeneity.

Objective: To investigate the effect of Tiaobu Xinshen Recipe (TXR) on cognitive function of 5xFAD transgenic mice and explore the potential mechanisms.

Methods: Six-month-old male wild-type (WT) mice and 5xFAD transgenic mice were randomly divided into vehicle (0.9% NaCl), TXR (granules, 4.18 g/kg) and donepezil (0.625 mg/kg) groups using a random number table, respectively, which were given intragastric administration once a day for 60 d. Spatial learning and memory performance was tested with modified Morris water maze (MMWM) test. Synaptic ultrastructure in the hippocampal CA1 region was observed by transmission electron microscopy. The levels of amyloid β (Aβ), the major amyloid precursor protein (APP)-cleaving enzymes and Aβ-degrading enzymes including β-secretase, α-secretase, neprilysin (NEP) and insulin-degrading enzyme (IDE), were detected by immunohistochemistry staining and Western blot, respectively.

Results: In MMWM test, when compared with the 5xFAD-vehicle group, 5xFAD-TXR group demonstrated a significantly shorter escape latency to the platform and increased number of platform crossings and time spent in target quadrant (P<0.05 or P<0.01). The ultrastructure of synapse in the hippocampal CA1 region of mice in the 5xFAD-TXR group was significantly changed, including increased numbers of mitochondria and synaptic vesicles, intact synaptic membrane, and thickened postsynaptic density. The Aβ load was markedly decreased in the cerebral cortex and hippocampus CA1 subregion of TXR-treated 5xFAD mice (P<0.05). TXR treatment decreased APP levels and increased IDE expression in brains of 5xFAD mice (P<0.01). However, TXR treatment had no effect on α- and β-secretase, and NEP in 5xFAD mice (P>0.05).

Conclusion: TXR improves cognitive dysfunction in 5xFAD mice by alleviating synaptic ultrastructure degradation and reducing Aβ.

Objective: To investigate therapeutic effects of Huanglian Jiedu Decoction (HLJDD) on metabolic-associated fatty liver disease (MAFLD) and explore its underlying mechanisms.

Methods: Q-Orbitrap liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify the incoming blood compounds of HLJDD. In vivo, high-fat diet (HFD)-induced MAFLD rats received HLJDD (5.4, 2.7, 1.35 g/kg) or silybin (37.8 mg/kg) once daily for 6 weeks. The rats fed with normal diets were served as control. Serum lipids were biochemically determined; and hepatic steatosis and lipid accumulation were evaluated with H&E and Oil red O stainings. In vitro, palmitic acid (PA)-treated HepG2 cells were co-incubated with 10% HLJDD drug-containing serum. Intracellular triglyceride (TG), total cholesterol (TC) and nonesterified fatty acids (NEFA) levels were detected and lipid droplet changes in HepG2 cells were observed by Oil red O staining. RT-qPCR and Western blot were employed to assess the expressions of lipid metabolic-related genes [diacylglycerol acyltransferase 2 (DGAT2), stearoyl-coenzyme A desaturase 1 (SCD1)] and components of the inositol-requiring enzyme 1alpha/X-box-binding protein-1 spliced (IRE1α/XBP1s) signaling pathway.

Results: A total of 43 active compounds of HLJDD were identified. In HFD-fed rats, HLJDD treatment significantly improved hepatic TG and TC and increased HDL-C level (P<0.05 or P<0.01), and also markedly reduced serum levels of TG, TC, LDL-C, ALT, and AST (P<0.05 or P<0.01). H&E and Oil red O stainings further revealed that HLJDD effectively alleviated hepatic steatosis and attenuated lipid accumulation in the liver tissues. In PA-treated HepG2 cells, HLJDD treatment significantly reduced intracellular levels of TG, TC, and NEFA (P<0.05 or P<0.01), as well as lipid accumulation. More importantly, HLJDD treatment exerted therapeutic effects in both HFD-fed rats and PA-induced HepG2 cells by down-regulating lipid metabolic-related genes DGAT2, SCD1 and suppressing the IRE1α/XBP1s pathway related protein expressions (P<0.05 or P<0.01).

Conclusion: HLJDD ameliorates MAFLD by modulating lipid metabolism through IRE1α/XBP1s signaling pathway, providing pharmacological evidence for its clinical application.

Background: Postoperative gastrointestinal dysfunction (POGD) is a common complication following gastrointestinal tumor surgery, significantly impairing patient recovery and quality of life. The efficacy of acupuncture in improving POGD remains unclear.

Objective: To evaluate the role of acupuncture in enhancing postoperative gastrointestinal function in patients with gastrointestinal tumors, providing evidence-based clinical insights.

Methods: Relevant studies were searched in PubMed, Cochrane Library, EMbase, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and VIP Database from inception to December 4, 2024. Only clinical-type studies involving acupuncture or electroacupuncture in the treatment of patients with gastrointestinal tumors were included. The primary outcomes were the first flatus time, first bowel movement time, first oral feeding, and hospitalization time. Secondary outcomes included white blood cell (WBC) count and C-reactive protein (CRP) level. Study quality was appraised using the domain-based evaluation described in the Cochrane Handbook.

Results: This study included 8 randomized control trials (CRCTs) involving 413 patients. Meta-analysis revealed that acupuncture significantly reduced the time to first flatus (P<0.05), time to first oral feeding (P<0.05), and hospital stay (P<0.05). However, it did not significantly affect the time to first bowel movement (P=0.53). Additionally, acupuncture significantly decreased CRP levels at 3 and 6/7 d postoperatively (P<0.05), as well as WBC counts at 6/7 d (P<0.05). The overall risk of bias of the included studies was rated as low to unclear.

Conclusions: Current evidence supports acupuncture as an effective adjunctive treatment for improving postoperative POGD in patients with gastrointestinal tumors. Further, high-quality RCTs are needed to validate these findings and optimize clinical protocols. (Registration No. CRD420250651195).

Objective: To investigate the effect and safety of Andrographolide Sulfonate (AS) Injection for adjunctive treatment of non-severe community-acquired pneumonia (CAP) in adults.

Methods: This is a multicenter, randomized, double-blind, and placebo-controlled trial. Adult patients with non-severe CAP were randomly assigned in a 1:1 ratio to the AS or control group using a stratified block randomization method. Patients received either intravenous AS Injection (500 mg once per day) or placebo for 5 d. Both groups were treated with guideline-based standard therapy simultaneously. The primary outcome was time to clinical stability. Secondary outcomes were initial treatment failure rate, time to fever recovery, length of hospital stay, duration of intravenous antibiotic treatment, and cost of hospitalization. Safety outcomes included adverse events (AEs) and serious AEs.

Results: From September 2016 to April 2019, 482 patients were randomized into AS or control group (241 cases per group), and all were included in the intention-to-treat (ITT) analysis. The median time to clinical stability was 1 h shorter in the AS group than that in the control group [hazard ratio (HR) 1.440; 95% confidence interval (CI) 1.194, 1.736; log rank P<0.01]. AS group had 5 h shorter median time to fever recovery than the control group (HR 1.461; 95% CI 1.150, 1.857; log rank P<0.01). The initial treatment failure rate was significantly lower in the AS group than that in the control group (6.3% vs. 16.0%, P<0.01). There was no statistically significant difference in the length of hospital stay, duration of intravenous antibiotics treatment, and cost of hospitalization between groups (P>0.05). The proportion of patients with at least 1 AE was 41.5% in the AS group and 40.6% in the control group.

Conclusions: Adjunctive AS Injection probably accelerates the clinical stability and lowers the initial treatment failure rate in adult hospitalized patients with non-severe CAP, but the absolute clinical benefits are marginal. Its use should take into account efficacy, safety, cost, and Chinese medicine syndrome classification. (Trial registration No. NCT02913118).

Objective: To investigate the action mechanism of Polygonatum sibiricum polysaccharides (PSP) in Alzheimer's disease (AD).

Methods: Network pharmacology and molecular docking was used to identify the major active ingredients and potential targets of PSP in treating AD. Male Kunming mice were randomly divided into 6 groups by a simple randomization method: control, model, low-, medium-, and high-dose PSP, and donepezil groups (n=6 per group). An AD mice model was established by intraperitoneally injecting 120 mg/kg D-galactose and oral administration of 40 mg/kg AlCl₃ for 70 d. PSP (100, 200, and 400 mg/kg) and donepezil (5 mg/kg) was administered orally for 35 d, respectively. Behavioral tests including the open field test, elevated plus maze, Morris water maze, and shuttle box test were performed to evaluate anxiety levels and learning and memory abilities. Western blot analysis was used to detect the phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signalling pathway activation. Leptin receptor (LepR) and neuronal nuclei (NeuN) co-localization was observed by immunofluorescence. Adeno-associated virus serotype 9 (AAV9)-mediated LepR knockdown (LepR-KD) was used to investigate the role of LepR in PSP-mediated cognitive improvement in AD mice and LepR and NeuN co-localization in the cerebral cortex. Immunohistochemistry was used to assess Tau protein deposition in the cortices of AD mice. Enzyme-linked immunosorbent assay quantified pro-inflammatory cytokines levels in the brain tissue.

Results: Network pharmacology identified that PI3K-AKT was the key signalling pathway affected by PSP in AD mice. In vivo experiments showed that PSP significantly improved anxiety levels and cognitive learning abilities in AD mice, upregulated the expression ratios of p-PI3K/PI3K and p-AKT/AKT in brain tissue, enhanced the activity of LepR and NeuN, and reduced Tau protein accumulation and the expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (P<0.05 or P<0.01). LepR-KD further demonstrated that its deficiency attenuated PSP's neuroprotective effects on cognitive function and cortical neuronal survival.

Conclusion: PSP modulates the PI3K-AKT signalling pathway in a LepR-dependent manner, thereby attenuating aberrant Tau protein deposition and inflammatory cytokine activity, which may cause delayed AD pathogenesis.