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Mechanistic study on combined application of Puerariae Lobatae Radix polysaccharide and betaine in ameliorating hepatic and intestinal injury via regulating TLR4 signaling pathway in alcoholic liver disease mice

Zhongguo Zhong Yao Za Zhi. 2025 Dec;50(23):6666-6676. doi: 10.19540/j.cnki.cjcmm.20250725.703.

ABSTRACT

This study aims to investigate the synergistic protective effects and underlying mechanisms of the combined application of Puerariae Lobatae Radix polysaccharide 1(PLP1) and betaine in alcohol-induced liver and intestinal injuries in mice and AML-12 hepatocytes. An alcoholic liver disease(ALD) mouse model was established according to the NIAAA protocol using chronic ethanol feeding combined with acute ethanol gavage. Mice were randomly divided into six groups: control, model, PLP1 monotherapy, betaine monotherapy, low-dose combination(LD-Comb), and high-dose combination(HD-Comb). Complementary in vitro studies involved ethanol-injured AML-12 mouse hepatocytes, divided into eight groups: control, model, PLP1, betaine, LD-Comb, medium-dose(MD-Comb), HD-Comb, and LD-Comb + lipopolysaccharide(LPS, 1 μg·mL~(-1)). Hepatic and intestinal histopathological changes were evaluated using hematoxylin-eosin(HE) staining, Sirius red staining, and immunohistochemistry. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), alcohol dehydrogenase(ADH), and aldehyde dehydrogenase(ALDH) were quantified by biochemical assays. Enzyme-linked immunosorbent assays(ELISA) measured tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), interleukin-1β(IL-1β), and LPS levels. Protein expressions of cytochrome P450 2E1(CYP2E1), zonula occludens-1(ZO-1), Occludin, mucin-2(MUC-2), Toll-like receptor 4(TLR4), nuclear factor-κB(NF-κB), and myeloid differentiation primary response 88(MyD88) were analyzed using Western blot, immunohistochemistry, and immunofluorescence. The mRNA expression of TLR4, NF-κB, and MyD88 was analyzed by quantitative PCR(qPCR). The results showed that, compared with the model group, PLP1 or betaine monotherapy significantly alleviated hepatic edema and inflammatory infiltration, reduced collagen deposition, increased intestinal mucus thickness, restored goblet cell count, and decreased serum levels of IL-6, TNF-α, IL-1β, LPS, ALT, and AST, while enhancing ADH and ALDH activity. Concurrently, CYP2E1, TLR4, NF-κB, and MyD88 expression levels were downregulated, and the expression of ZO-1, occludin, and MUC-2 in colon tissues was upregulated. The combined treatment of PLP1 and betaine further enhanced these improvements compared with monotherapies, although the difference between the LD-Comb and HD-Comb groups was not statistically significant. In AML-12 cells, PLP1 or betaine monotherapy significantly reduced ALT, AST, IL-6, and TNF-α levels in the culture supernatant and downregulated the expression of TLR4, NF-κB, and MyD88. The combined treatment showed stronger effects than monotherapy, while co-treatment with the TLR4 agonist LPS partially reversed these benefits. In conclusion, the combination of PLP1 and betaine exerts synergistic protective effects by enhancing ethanol metabolism, promoting tight junction protein synthesis, repairing intestinal barrier function, reducing LPS translocation, and suppressing the activation of the TLR4 signaling pathway, thereby lowering inflammatory cytokine levels. This multi-targeted synergy effectively alleviates liver and intestinal injury in ALD mice and ethanol-injured AML-12 hepatocytes.

PMID:41508269 | DOI:10.19540/j.cnki.cjcmm.20250725.703

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Number of traditional Chinese medicines in Essentials of Materia Medica Distinctions of Roman version and some herbal textual research

Zhongguo Zhong Yao Za Zhi. 2025 Oct;50(19):5584-5604. doi: 10.19540/j.cnki.cjcmm.20250516.101.

ABSTRACT

This study was based on the photoreprint of the Ming dynasty’s officially revised Essentials of Materia Medica Distinctions(hereinafter referred to as the Roman version) held in the National Central Library of Rome, Italy. It examined the number of traditional Chinese medicines(TCMs) recorded, TCM adjustment status, the origins of newly added TCMs, and the characteristics of some TCM illustrations in this version. The study aimed to provide reference for the subsequent research and utilization of Essentials of Materia Medica Distinctions. The study employed methods of literature statistics, induction, and herbal textual research to investigate the number of TCMs recorded in the book, the adjustments, the origins of newly added TCMs, and the origins of some TCMs in the illustrations. The Roman version actually recorded 1 808 TCMs. Compared with The Revised Zhenghe Classified Materia Medica from Historical Classics for Emergency, it included 38 newly added TCMs marked as "newly supplemented TCMs", 23 TCMs marked as "newly separated entries" which were split from existing entries, 31 TCMs that were adjusted, and 422 TCMs with newly added illustrations. The origins of the 38 newly supplemented TCMs and 23 newly separated entries were identified. The rationality of TCM separation and movement was evaluated, and the characteristics of the TCM illustrations in Essentials of Materia Medica Distinctions were summarized. By sorting out the number of TCMs, analyzing the adjustments, examining the newly supplemented TCMs and their origins, and investigating the characteristics of TCM illustrations, this study provides reference for the compilation, structure, versions, TCM collection, reading, and utilization of Essentials of Materia Medica Distinctions.

PMID:41508249 | DOI:10.19540/j.cnki.cjcmm.20250516.101

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Study on law of syndrome differentiation and treatment of epilepsy and discovery of effective prescriptions based on ancient medical records

Zhongguo Zhong Yao Za Zhi. 2025 Oct;50(20):5882-5895. doi: 10.19540/j.cnki.cjcmm.20250708.501.

ABSTRACT

Based on the ancient books, data mining of ancient medical records of epilepsy was carried out. The law of syndrome differentiation and treatment of epilepsy in ancient medical records was summarized, and effective prescriptions and core formulas were excavated, so as to provide reference for clinical treatment of epilepsy. Apriori algorithm module in IBM SPSS Modeler 18.0 was used to analyze the association rules of syndrome elements in ancient medical records of epilepsy. Fruchterman-Reingold network layout algorithm in Gephi 0.10.1 software was utilized to analyze the complex network of syndrome elements in ancient medical records of epilepsy, and the Pearson correlation coefficient in the measuring interval of SPSS Statistics 29.0 was employed to perform hierarchical cluster analysis on syndrome elements in ancient medical records of epilepsy. The law of syndrome differentiation and treatment was summarized, and effective prescriptions were explored. Through the statistical analysis of 117 ancient medical records of epilepsy, 22 disease nature syndrome elements, 10 disease location syndrome elements, and 4 emotional syndrome elements were extracted. Seventy-seven ancient medical records of epilepsy during the seizure period were included, with 71 medical records containing disease nature, 49 medical records containing disease location, and 11 medical records containing emotional elements. Twenty-nine ancient medical records of epilepsy during the resting period were included, with 23 medical records containing disease nature, 17 medical records containing disease location, and 6 medical records containing emotional elements. Through the compatibility analysis of syndrome elements, 6 association rules of disease location-nature during the seizure period, 13 association rules of disease location-nature, and 3 association rules of disease location-nature during the resting period were obtained. The Fruchterman-Reingold network layout algorithm in Gephi 0.10.1 software was used to visually analyze the syndrome elements in 70 medical records, disease location and nature in 49 medical records during the seizure period, and disease location and nature in 15 medical records during the seizure period. A total of 239 traditional Chinese medicines(TCMs) were obtained. The Pearson correlation coefficient in the measuring interval of SPSS Statistics 29.0 was used for linkage cluster analysis of TCM administered during the seizure period(frequency≥10) and the resting period(frequency≥4) in ancient medical records of epilepsy. With a cluster spacing of 24, the seizure period was divided into 2 groups, and the resting period was divided into 2 groups. The law of syndrome differentiation and treatment of epilepsy was that the liver-gallbladder fire was excessive, and the phlegm-fire disturbed the nerves in the whole process of epilepsy. The treatment was mainly resolving phlegm and soothing the nerve. The seizure period was characterized by wind-phlegm disturbing the brain and blinding the brain. The treatment was mainly eliminating phlegm and clearing fire as well as dispelling wind and calming convulsion, and the core formula was a modified combination of Changpu Yujin Decoction combind Lingjiao Gouteng Decoction and Erchen Decoction. The resting period was characterized by Yin deficiency of the liver and kidney, spleen deficiency, and excessive phlegm. The treatment was mainly eliminating phlegm and clearing fire as well as replenishing deficiency and nourishing Yin, and the core formula was a modified combination of Congming Decoction combind Zhusha Anshen Pills.

PMID:41508219 | DOI:10.19540/j.cnki.cjcmm.20250708.501

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Metabolite characteristics analysis of cultivated and wild Rehmannia glutinosa based on LC-MS combined with multivariate statistical analysis

Zhongguo Zhong Yao Za Zhi. 2025 Oct;50(20):5706-5716. doi: 10.19540/j.cnki.cjcmm.20250604.101.

ABSTRACT

To analyze the difference of overall metabolites in cultivated and wild Rehmannia glutinosa, this study used cultivated and wild R. glutinosa from different locations as research objects. Their metabolites were detected using liquid chromatography-mass spectrometry(LC-MS), and multivariate statistical analysis was adopted to analyze metabolites. Differential metabolites were identified, and differential metabolic pathways were determined based on the Kyoto Encyclopedia of Genes and Genomes(KEGG) database. The results showcased that 1 802 metabolites were detected, and the metabolites of cultivated and wild R. glutinosa were similar, including 13 kinds of compounds such as terpenoids, phenolic acids, lipids, and alkaloids. Overall, the relative content of metabolites of wild R. glutinosa was higher than that of cultivated R. glutinosa. There were 665 differential metabolites between cultivated and wild R. glutinosa. A total of 157 differential metabolites were up-regulated, and 508 differential metabolites were down-regulated. According to the KEGG database, 93 metabolites with significant differences were annotated, with phenolic acids representing the highest proportion. There were a total of 55 metabolic pathways corresponding to differential metabolites, which were divided into three categories: metabolism, genetic information processing, and environmental information processing. Significantly different pathways included flavonoid biosynthesis(ko00941), phenylpropane biosynthesis(ko00940), and pyrimidine metabolism(ko00240), all of which were associated with plant metabolism. The study found that the metabolite species of wild and cultivated R. glutinosa were consistent, whereas the overall metabolite content of wild R. glutinosa was higher than that of cultivated R. glutinosa, and the difference in their pharmacological effects remained to be further investigated.

PMID:41508202 | DOI:10.19540/j.cnki.cjcmm.20250604.101

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Prospects for development of new traditional Chinese medicine drugs based on human use experience empowered by artificial intelligence

Zhongguo Zhong Yao Za Zhi. 2025 Oct;50(20):5605-5612. doi: 10.19540/j.cnki.cjcmm.20250708.601.

ABSTRACT

The development of traditional Chinese medicine(TCM) new drugs is undergoing profound transformation under the increasingly rigorous global standards of evidence-based medicine and drug regulatory science. A full-cycle R&D model based on human use experience(HUE) has emerged as a strategic bridge linking TCM theory, historical usage, clinical evaluation, and innovative drug development. On this foundation, artificial intelligence(AI) is empowering all stages of TCM new drug development with unprecedented depth. These include: semantic understanding, reconstruction, and dialogue of literature based on natural language processing(NLP) and large language models(LLMs); safety modeling and druggability assessment driven by statistical learning, including deep learning; syndrome objectification via multimodal learning that integrating heterogeneous data such as tongue images, pulse patterns, and electronic medical records; and intelligent optimization of clinical research through adaptive trial design, platform trials, and reinforcement learning. This paper systematically reviews the critical roles of AI throughout the TCM new drug lifecycle-from candidate selection, HUE-based evidence structuring, and safety prediction, to clinical trial design, regulatory submission, post-marketing risk identification, and secondary development-highlighting the paradigm shift enabled by the deep integration of AI and HUE. It further proposes the construction of an integrated intelligent TCM new drug development platform that forms a closed-loop system of "data-driven, model-supported, and intelligent decision-making", promoting the transformation of TCM R&D from empirical reasoning to one driven by high-dimensional knowledge graphs, expert-AI collaborative learning, and multi-source evidence integration. Looking forward, AI is expected to further facilitate individualized therapeutic modeling, intelligent optimization of herbal compatibility strategies, repositioning of indications for compound formulas, and intelligent alignment with international regulatory pathways. This will accelerate the establishment of an internationally adaptive and standardized intelligent TCM new drug development system. This study provides both a theoretical foundation and practical direction for building a future-oriented innovation ecosystem and enhancing the global competitiveness of China’s TCM new drug industry.

PMID:41508193 | DOI:10.19540/j.cnki.cjcmm.20250708.601

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Suitability zoning of Saposhnikovia divaricata in Mongolia under climate change based on MaxEnt model and Biomod2 ensemble model

Zhongguo Zhong Yao Za Zhi. 2025 Nov;50(21):6008-6016. doi: 10.19540/j.cnki.cjcmm.20250702.101.

ABSTRACT

Medicinal plants represent a critical component of natural resources and play a vital role in global healthcare and therapeutic systems. Saposhnikovia divaricata, a well-known traditional medicinal plant, exhibits ecological and quality suitability that is strongly influenced by various environmental factors. To investigate the suitable distribution and accumulation patterns of active components in S. divaricata in Mongolia, this study integrated climatic, soil, and topographic variables to evaluate its habitat suitability by using both the MaxEnt model and the Biomod2 ensemble modeling approach. The predictive performance of the two models was compared. High-performance liquid chromatography(HPLC) was employed to quantify the active components in collected S. divaricata samples, enabling a comprehensive quality assessment. The results demonstrated that the MaxEnt model achieved an area under curve(AUC) of 0.933 and a true skill statistic(TSS) value of 0.737, while the Biomod2 ensemble model showed improved performance with an AUC of 0.957 and a TSS value of 0.741. The most suitable regions for the growth of S. divaricata were identified as Dornod, Khentii, Selenge, Darkhan-Uul, Bulgan, Orkhon, and T9v provinces. Ecological suitability was primarily influenced by elevation(ELEVATION), precipitation during the warmest quarter(BIO18), and annual mean temperature(BIO1). The accumulation of prim-O-glucosylcimifugin was closely related to temperature, precipitation, and soil particle size, while the content of 5-O-methylvisammioside was largely influenced by precipitation and soil physicochemical properties, including base saturation, aluminum saturation, and cation exchange capacity. This study provides guidance for seed introduction, cultivation, and standardized production of S. divaricata in Mongolia.

PMID:41508172 | DOI:10.19540/j.cnki.cjcmm.20250702.101

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Rapid evaluation of frying degree of Ziziphi Spinosae Semen based on spectrophotometry and near-infrared spectroscopy combined with multivariate mathematical statistics

Zhongguo Zhong Yao Za Zhi. 2025 Nov;50(21):5928-5938. doi: 10.19540/j.cnki.cjcmm.20250402.301.

ABSTRACT

To rapidly evaluate Ziziphi Spinosae Semen samples with different frying degrees, this study employed a CM-5 spectrophotometer to detect the dynamic color changes during the frying process. Near-infrared spectroscopy was utilized to measure Ziziphi Spinosae Semen samples at different frying degrees via diffuse reflectance. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were combined to quickly assess the quality of Ziziphi Spinosae Semen at different frying degrees. The results showed that with prolonged frying time, the brightness of Ziziphi Spinosae Semen decreased slightly, while the red and yellow hues became more pronounced, and color saturation increased. The saturation value(C~*), yellow-blue value(b~*), and red-green value(a~*) were the primary variables contributing to the color difference between raw and fried Ziziphi Spinosae Semen. The OPLS-DA model was employed to distinguish between raw and fried Ziziphi Spinosae Semen based on color parameters. The near-infrared raw spectra of Ziziphi Spinosae Semen samples with varying frying degrees were pretreated and optimized using multiple scatter correction(MSC) and competitive adaptive reweighted sampling(CARS). The PLS-DA model effectively differentiated samples with different frying degrees. The R~2 values for both the calibration and prediction sets of the discrimination model were greater than 0.90, indicating good discriminative capability. This study achieved rapid evaluation of different frying degrees of Ziziphi Spinosae Semen decoction pieces and provides a scientific reference for quality control during the processing of fried Ziziphi Spinosae Semen decoction pieces.

PMID:41508164 | DOI:10.19540/j.cnki.cjcmm.20250402.301

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Association between low-density lipoprotein and structural changes in the knee joint of patients with symptomatic osteoarthritis is mediated by relative fat mass

Eur J Med Res. 2026 Jan 8. doi: 10.1186/s40001-025-03826-3. Online ahead of print.

ABSTRACT

BACKGROUND: Knee osteoarthritis (KOA) is strongly associated with obesity, yet body mass index (BMI) fails to capture fat distribution or metabolic activity, limiting its utility in understanding KOA pathogenesis. Relative fat mass (RFM), a novel estimator of whole-body fat percentage derived from waist circumference and height, may provide a more accurate assessment of adiposity and its metabolic consequences.

OBJECTIVE: This study aimed to compare RFM and BMI in predicting MRI-detected structural changes in KOA and to investigate whether RFM statistically mediates the association between low-density lipoprotein (LDL) and cartilage degeneration.

METHODS: A retrospective analysis of 184 patients with symptomatic KOA was performed. BMI, RFM, and serum lipid profiles were measured. MRI assessments included cartilage volume, cartilage defects, and bone marrow lesions. Multivariable regression and ROC analysis evaluated predictive performance, while mediation analysis tested RFM’s role in the LDL-cartilage volume relationship.

RESULTS: RFM and BMI showed moderate correlation (r = 0.600, P < 0.001). RFM demonstrated significantly stronger associations with cartilage volume loss than BMI, particularly for patellar cartilage (RFM: β = -0.038, P < 0.001; BMI: P > 0.05). ROC analysis confirmed RFM’s superior predictive ability for patellar cartilage volume (AUC = 0.681 vs. 0.525). Mediation analysis revealed that the association between LDL and patellar cartilage volume showed a statistically significant indirect effect through RFM (indirect effect =- 0.071, 95% CI -0.133 to-0.008, proportion mediated = 72.4%). Sex-stratified analyses showed consistent associations in females (P < 0.001) with no significant RFM × sex interaction (P = 0.68).

CONCLUSION: RFM outperforms BMI in predicting structural damage in KOA, particularly cartilage volume loss. The identified statistically significant indirect pathway (LDL → RFM → cartilage volume) provides a novel framework for understanding how dyslipidemia may be associated with cartilage degeneration through adiposity, offering potential targets for metabolic intervention strategies in KOA prevention.

PMID:41508160 | DOI:10.1186/s40001-025-03826-3

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DLGAP5 Drives Lung Cancer Progression: Combined Bioinformatics and Clinical Prognostic Analysis

J Immunother. 2026 Jan 9. doi: 10.1097/CJI.0000000000000597. Online ahead of print.

ABSTRACT

DLGAP5 has emerged as a potential biomarker implicated in tumor progression across various cancers, yet its prognostic value in lung cancer remains to be fully elucidated. In this study, we integrated comprehensive bioinformatics analyses with clinical data to investigate the expression patterns of DLGAP5 and its association with patient outcomes in lung cancer. Expression profiling revealed that DLGAP5 levels varied modestly across clinical subgroups defined by age, sex, tumor stage, and grade, with no statistically significant differences observed. Survival analyses demonstrated that elevated DLGAP5 expression was significantly correlated with reduced overall survival, while disease-free survival showed no marked difference. Multivariate Cox regression and clinical prognostic models further confirmed DLGAP5 as an independent risk factor associated with poorer prognosis (HR=2.35, 95% CI: 1.10-5.03, P=0.021). Functional enrichment analyses of differentially expressed genes between the low-DLGAP5 expression group and high-DLGAP5 expression group identified key biological processes and pathways, including transcriptional regulation and cytoskeletal organization, potentially mediating DLGAP5’s role in lung cancer progression. These findings provide robust evidence supporting the prognostic relevance of DLGAP5 in lung cancer and underscore its potential utility as a therapeutic target.

PMID:41508152 | DOI:10.1097/CJI.0000000000000597

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Reviewing inclusivity of the UK bladder and head and neck oncology trial portfolio through eligibility criteria and demographic data collection: a scoping review

Trials. 2026 Jan 8. doi: 10.1186/s13063-026-09424-w. Online ahead of print.

ABSTRACT

BACKGROUND: In clinical trials, eligibility criteria define a population who may benefit from the intervention without incurring undue safety risks. Despite their value, overly stringent eligibility criteria may pose barriers to inclusive recruitment. They may disproportionately exclude groups of people more likely to be diagnosed at later cancer stages, or have specific co-morbidities which can be associated with socio-demographic or ethnic background. The National Institute for Health and Care Research Innovations in Clinical Trial Design and Delivery for the Under-served (NIHR-INCLUDE) guidance highlighted several groups of people who may be underserved by clinical research. The aim of this review was to assess eligibility criteria in bladder and head and neck oncology trials and consider their potential impact on potentially underserved groups.

METHODS: This scoping review included multi-centre, interventional, phase II and III trials in bladder or head and neck cancer, which recruited UK participants between 2013 and 2023. Trials were identified via searches of ClinicalTrials.gov, the International Standard Randomised Controlled Trial Number (ISRCTN) registry, and NIHR Clinical Portfolio Management System (CPMS). Trials’ eligibility criteria were categorised and analysed narratively. Trial parameters (recruitment period, funding type, and whether they were of investigational medicinal products (IMPs)) were cross-tabulated with common exclusion criteria using Fisher’s exact test.

RESULTS: Thirty-eight bladder and 30 head and neck cancer trials met the selection criteria. Twenty-eight out of 68 (41%) had non-commercial sponsors. Fifty-six out of 68 (82%) were of IMPs. Forty-one out of 68 (60%) were industry-funded. Fifty-one out of 68 (75%) were for locally advanced, metastatic, or recurrent disease. Common exclusion criteria relating to pregnancy, performance status, HIV status, and cognitive ability may disproportionately impact some underserved groups suggested by the NIHR-INCLUDE guidance.

CONCLUSIONS: This review highlights common exclusion criteria which may disproportionately exclude underserved groups from UK bladder and head and neck oncology trials. To facilitate accessibility to oncology trials, sponsors and triallists should consider how potentially underrepresented groups may be safely included during development of eligibility criteria.

PMID:41508127 | DOI:10.1186/s13063-026-09424-w