Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

Traditional Chinese medicine(TCM) processing is a specialized pharmaceutical technique with the primary objective of reducing the toxicity of medicinal substances. Euphorbia pekinensis, E. ebracteolata, and E. fischeriana, all belonging to Euphorbiaceae, are classified as drastic purgative herbs, traditionally used for eliminating retained water, reducing swelling, resolving toxicity, and dispersing masses. However, these herbs are also associated with adverse effects such as abdominal pain and diarrhea. Accordingly, they are commonly processed with vinegar, milk, or Terminalia chebula decoction to reduce the toxicity. This review summarizes the chemical constituents, pharmacological activities, historical evolution of processing methods, and detoxification mechanisms of the three toxic Euphorbia species. The primary toxic constituents are terpenoids. Specifically, E. ebracteolata and E. fischeriana are rich in diterpenoids, while E. pekinensis contains diterpenoids, triterpenoids, and sesquiterpenoids. Studies have shown that vinegar processing promotes structural transformations of diterpenoids, including ether bond hydrolysis, lactone ring opening, esterification, oxidation, and epoxide ring cleavage, thereby reducing the content and toxicity of these compounds. Milk processing facilitates the dissolution of toxic components into the residual liquid of excipients, leading to decreases in their concentrations in the final decoction pieces. Processing with T. chebula decoction raises the levels of tannin-derived phenolic acids, which antagonize the adverse effects of the intestine. These findings reveal a shared detoxification pattern among the three toxic herbs. Accordingly, this review proposes the concept of a shared detoxification mechanism for toxic herbs belonging to the same family or genus. That is, toxic herbs belonging to the same taxon often exhibit similar toxicological profiles and can undergo detoxification through the same processing methods, reflecting common underlying mechanisms. Investigating such shared mechanisms across multiple species of the same genus offers a promising research strategy. Ultimately, the research into processing-induced detoxification mechanisms provides both theoretical and practical support for ensuring the safety of toxic TCM.
Euphorbia/classification* ; Drugs, Chinese Herbal/metabolism* ; Humans ; Animals ; Inactivation, Metabolic ; Medicine, Chinese Traditional

OBJECTIVE: To investigate the short-term effectiveness of uni-portal non-coaxial spinal endoscopic surgery (UNSES) via crossing midline approach (CMA) in the treatment of free lumbar disc herniation (FLDH). METHODS: Between March 2024 and June 2024, 16 patients with FLDH were admitted and treated with UNSES via CMA. There were 9 males and 7 females with an average age of 55.1 years (range, 47-62 years). The disease duration was 8-30 months (mean, 15.6 months). The pathological segments was L _{3, 4} in 4 cases, L _{4, 5} in 5 cases, and L ₅, S ₁ in 7 cases. The preoperative pain visual analogue scale (VAS) score was 6.9±0.9 and the Oswestry disability index (ODI) was 57.22%±4.16%. The operation time, intraoperative bleeding volume, postoperative hospital stay, and incidence of complications were recorded. The spinal pain and functional status were evaluated by VAS score and ODI, and effectiveness was evaluated according to the modified MacNab criteria. CT and MRI were used to evaluate the effect of nerve decompression. RESULTS: All 16 patients underwent operation successfully without any complications. The operation time was 63-81 minutes (mean, 71.0 minutes). The intraoperative bleeding volume was 47.3-59.0 mL (mean, 55.0 mL). The length of hospital stay after operation was 3-4 days (mean, 3.5 days). All patients were followed up 1-3 months, with 15 cases followed up for 2 months and 14 cases for 3 months. The VAS score and ODI gradually decreased over time after operation, and there were significant differences between different time points ( P<0.05). At 3 months after operation, the effectiveness was rated as excellent in 12 cases and good in 2 cases according to the modified MacNab criteria, with an excellent and good rate of 100%. CT and MRI during follow-up showed a significant increase in the diameter and cross-sectional area of the spinal canal, indicating effective decompression of the canal. CONCLUSION When using UNSES to treat FLDH, choosing CMA for nerve decompression has the advantages of wide decompression range, large operating space, and freedom of operation. It can maximize the preservation of the articular process, avoid fracture and breakage of the isthmus, clearly display the exiting and traversing nerve root, and achieve good short-term effectiveness.
Humans ; Male ; Intervertebral Disc Displacement/diagnostic imaging* ; Middle Aged ; Female ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Treatment Outcome ; Operative Time ; Pain Measurement ; Length of Stay

OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

The Baveno Cooperation is a consortium of internationally renowned experts committed to setting standards for the clinical management of patients with advanced chronic liver disease, with a particular emphasis on complications related to portal hypertension. Updated every five years and endorsed by major scientific societies, the Baveno recommendations have significantly influenced clinical practice and improved patient outcomes worldwide. The latest Baveno consensus, Baveno VII, provided a series of recommendations that have shifted our understanding of chronic liver disease and portal hypertension and profoundly shaped clinical practice. However, many areas of research remain to be explored in the short to intermediate term to enable a more personalized medicine approach. This review highlights some of the most relevant advancements introduced in Baveno VII and discusses future challenges.
Hypertension, Portal/therapy* ; Humans

Traditional Chinese medicine (TCM) exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets. However, the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians, which has been a major challenge in the global acceptance and application of TCM. Therefore, a standardized TCM prescription system needs to be explored to promote its clinical application. In this study, we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation. We tested its efficacy against intracerebral hemorrhage (ICH). First, the top 100 ICH targets in the GeneCards database were screened according to their relevance scores. Then, SymMap and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases were applied to find out the target-related ingredients and ingredient-containing herbs, respectively. The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets. The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions. The absorbed components in the serum were detected. In a mouse model of ICH, the new prescription exerted multifaceted effects, including improved neurological function, as well as attenuated neuronal damage, cell apoptosis, vascular leakage, and neuroinflammation. These effects matched well with the core pathological changes in ICH. The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise, multipronged, unbiased, and standardized TCM prescriptions for complex diseases. This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

BACKGROUND: Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias. OBJECTIVE: Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP). SEARCH STRATEGY: We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics. INCLUSION CRITERIA: Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review. DATA EXTRACTION AND ANALYSIS: Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment. RESULTS: A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41). CONCLUSION The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans ; Acupuncture Analgesia ; Acupuncture Therapy ; Anesthesia ; Clinical Trials as Topic ; Registries

Objective This study investigated the impact of occupational mercury(Hg)exposure on human gene transcription and expression,and its potential biological mechanisms. Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation.Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells.PTEN gene expression was assessed using qRT-PCR,and Western blotting was used to measure PTEN,AKT,and PI3K protein levels.IL-6 expression was determined by ELISA. Results Combined findings from gene expression microarray analysis,bioinformatics,and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group.In the Hg-exposed cell model(25 and 10 μmol/L),a significant decrease in PTEN expression was observed,accompanied by a significant increase in PI3K,AKT,and IL-6 expression.Similarly,a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K,AKT,and IL-6 levels. Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene,activates the PI3K/AKT regulatory pathway,and increases the expression of inflammatory factors,ultimately resulting in kidney inflammation.

A liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was developed for determination of three kinds of β-agonists(Clenbuterol(CL),Ractopamine(RAC)and Salbutamol(SAL))residues in animal liver samples.The liver sample homogenates were extracted with organic solvent,followed by clean-up using the automatic magnetic solid-phase extraction(MSPE),and then analyzed using LC-MS/MS.The results showed that the magnetic mixed-mode cation exchange adsorbent(M-MCX)exhibited 34%higher adsorption capacity than the conventional mixed-mode cation exchange(MCX)column.Furthermore,the clean-up was conducted by using an automatic MSPE device,and 8 samples could be simultaneously treated within 30 min.The limits of detection(LOD)were 0.01-0.1 μg/kg,the average recoveries ranged from 88.2%to 110.5%,and the relative standard deviations(RSDs)were in range of 2.9%-10.3%at three spiked levels for the three kinds of β-agonists.Compared with the traditional SPE technique,the present method had many advantages such as simple operation,rapidity and high efficiency,which was suitable for high-throughput and automatic detection of residues in routine analysis.