Despite breakthroughs in immunotherapy for solid tumors, significant variations in treatment efficacy persist. Up to 80% of cancer patients suffer from malnutrition, which leads to: lymphoid atrophy and reduced T-cell reserves; deficiency of substrates required for T-cell activation and expansion; concurrent inflammation hindering T-cell infiltration into tumors; and cachexia accelerating PD-1 antibody clearance. Clinical studies confirm that severe malnutrition significantly impairs immune responses and increases the risk of treatment toxicity. Therefore, implementing standardized nutritional therapy is crucial for optimizing the reserve, activation, expansion, and infiltration capacity of immune cells, thereby providing a sound immune system foundation for immunotherapy. Immunonutrition therapy, by enhancing immunonutrients such as arginine, omega-3 polyunsaturated fatty acids, and nucleotides, reduces the secretion of pro-inflammatory mediators and promotes T-cell activation and proliferation. This enhances anti-tumor immune responses, prolongs survival, and advances cancer treatment towards multimodal combination and precision approaches.

Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry* ; Plants, Medicinal/chemistry* ; Pentacyclic Triterpenes/pharmacology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals

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

Osteoporosis(OP) is a metabolic bone disorder characterized by reduced bone mass and degenerative bone tissue. Osteoporotic pain(OPP) is its most common clinical symptom, significantly affecting the quality of life of patients. With the limitations of modern medical treatments and the intensification of aging, it is imperative to explore more cost-effective interventions for OPP. This paper, based on databases such as China National Knowledge Infrastructure(CNKI), VIP, Wanfang, BioMed, and Web of Science, uncovered the connection between the pathogenesis of OPP in traditional Chinese medicine(TCM) and modern medical mechanisms and retrospectively summarized the basic and clinical research methods and evidence of TCM prescriptions in the treatment of OP and related pain diseases. Studies have shown that TCM prescriptions, focusing on treatments such as nourishing the kidney, strengthening the spleen, and activating blood circulation to remove blood stasis, can significantly improve pain symptoms, increase bone mineral density(BMD), and adjust bone metabolic indicators such as C-terminal telopeptide of type Ⅰ collagen(CTX), serum bone Gla-protein(S-BGP), and alkaline phosphatase(ALP). The mechanisms of action of TCM prescriptions in treating OP and improving OPP symptoms were related to signaling pathways such as Wnt/β-catenin, nuclear factor kappa-B(NF-κB), mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), and the osteoprotegerin(OPG)/receptor activator of NF-κB(RANK)/receptor activator of NF-κB ligand(RANKL) axis. Further strengthening the accumulation and analysis of clinical data, rigorously designing and conducting randomized controlled trials of TCM treatments for OPP with large sample sizes, standardizing outcome measures in basic and clinical research by using methods such as the core outcome set(COS), and incorporating mass spectrometry and omics approaches to uncover more potential active components and mechanisms may contribute to a deeper exploration of the advantages and essence of TCM prescriptions in the treatment of OPP.
Humans ; Osteoporosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Retrospective Studies ; Bone Density/drug effects* ; Medicine, Chinese Traditional ; Pain/metabolism* ; Animals

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

BACKGROUND:Studies have shown that patients with premature ovarian failure have changes in the structure of intestinal flora and that imbalance of intestinal microbiota may be one of the important mechanisms in the development of premature ovarian failure. OBJECTIVE:To investigate the effect of Liuwei Dihuang Wan on oxidative stress and intestinal microbiota in premature ovarian failure mice induced by cyclophosphamide. METHODS:Forty-five female ICR mice were randomized into three groups:blank group(normal mice),model group(premature ovarian failure mice),and Liuwei Dihuang Wan group.A mouse model of premature ovarian failure was prepared by one-time intraperitoneal injection of cyclophosphamide(120 mg/kg)in the latter two groups.After successful modeling,the Liuwei Dihuang Wan group was intragastrically administered for 28 continuous days,and the other two groups were intragastrically administered with the same amount of normal saline for 28 days.Mouse body mass was recorded weekly and ovarian index was calculated.The development of mouse follicles was observed using hematoxylin-eosin staining.ELISA method was used to detect serum levels of anti-Mullerian hormone,estradiol,follicle stimulating hormone,superoxide dismutase,glutathione peroxidase,and malondialdehyde.Meanwhile,the gut microbiome of all mice was detected through 16S rDNA sequencing. RESULTS AND CONCLUSION:The mice in the model group had loose hair,decreased vigor and grip strength,almost no increase in body mass,and decreased ovarian index.Whereas,the mouse body mass and ovarian index were increased after treatment with Liuwei Dihuang Wan(P<0.05).The estrous cycle of mice in the model group was disorganized;Liuwei Dihuang Wan could restore the estrous cycle and reduce the number of atretic follicles in mice with premature ovarian failure.The serum levels of follicle stimulating hormone and malondialdehyde in the model group significantly increased(P<0.01),while the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase significantly decreased(P<0.01).Liuwei Dihuang Wan could significantly decrease the serum levels of follicle stimulating hormone and malondialdehyde(P<0.01),and increase the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase.According to the 16S rDNA sequencing results,Liuwei Dihuang Wan could regulate the abundance and diversity of intestinal microbiota,and increase the relative abundance of beneficial bacteria.KEGG pathway analysis showed that the intestinal microbiota and metabolic pathways,biosynthesis of secondary metabolites,microbial metabolism in different environments,and biosynthesis of amino acids were regulated by Liuwei Dihuang Wan.To conclude,the changes in the structure of intestinal microbiome may be one of the potential mechanisms of Liuwei Dihuang Wan in treating premature ovarian failure.Liuwei Dihuang Wan can regulate the structure of intestinal microbiome,increase the number of beneficial bacteria,reduce the number of harmful bacteria,and thus improve the balance of intestinal microbiota.This regulatory effect helps to reduce oxidative stress levels and further inhibit ovarian oxidative stress in mice with premature ovarian failure.

OBJECTIVE To evaluate the efficacy， safety and economy of inclisiran in the treatment of atherosclerotic cardiovascular disease with hypercholesterolemia. METHODS A rapid health technology assessment （HTA） approach was employed. HTA reports， systematic reviews（SR）/meta-analyses， and pharmacoeconomic studies related to inclisiran were systematically identified through comprehensive searches of Chinese and English databases， including PubMed， Embase， the Cochrane Library， CNKI and Wanfang database， supplemented by HTA institutional repositories. The search timeframe spanned from database inception to April 2025. The results of the studies were descriptively analysed and summarized through literature screening， data extraction and literature quality assessment. RESULTS The final analysis included 22 studies， comprising one HTA report， 15 SR/meta-analyses， and 6 pharmacoeconomic evaluations. Regarding therapeutic efficacy， compared with control group， inclisiran could significantly reduce the levels of low-density lipoprotein cholesterol， proprotein convertase subtilisin/kexin type 9， total cholesterol， triacylglycerol， apolipoprotein B， and lipoprotein（a）， increase the level of high-density lipoprotein cholesterol， and reduce the risk of adverse cardiovascular events. In terms of safety， the inclisiran group showed no significant difference compared with the control group in the risk of total adverse events， serious adverse events， or non-serious adverse events； however， an increased incidence of injection site reactions was observed， most of which were mild. In terms of cost-effectiveness， there were discrepancies in research conclusions both domestically and internationally. More studies indicated that inclisiran did not demonstrate cost-effectiveness advantage and would require an appropriate price reduction to meet cost-effectiveness criteria. CONCLUSIONS Inclisiran demonstrates favorable efficacy and acceptable safety in treating atherosclerotic cardiovascular disease with hypercholesterolemia， though its economic profile requires improvement.

Objective: To investigate the age, period, and birth cohort effect of the incidence, mortality, and disability-adjusted life years (DALY) of oral cancer among the Chinese elderly from 1992 to 2021. Methods: Data on oral cancer incidence, mortality, and DALY rate in the Chinese population aged ≥60 years from 1992 to 2021 were collected from the Global Burden of Disease 2021 (GBD 2021) database. The trends in the incidence, mortality, and DALY rate of oral cancer were analyzed using the average annual percent change (AAPC) and the age-period-cohort (APC) model. Results: The incidence, mortality, and DALY rates of oral cancer among the Chinese elderly showed increasing trends (AAPC=2.262%, 0.548% and 0.360%, all P<0.05) from 1992 to 2021. The APC model revealed that the incidence, mortality, and DALY rate of oral cancer increased with age, peaking in the 85-<90 age group at 22.31/100 000, 16.69/100 000, and 171.41/100 000, respectively. Using the period 2002-2006 as the reference group, the risks of incidence, mortality, and disability of oral cancer showed increasing trends over time. The highest risk of incidence was observed in 2017-2021 (RR=1.450, 95%CI: 1.398-1.504), while the peak risks of mortality (RR=1.131, 95%CI: 1.097-1.166) and disability (RR=1.146, 95%CI: 1.118-1.175) both occurred in 2012-2016. With the 1925-1929 birth cohort as the reference group, the risk of oral cancer incidence showed an increasing trend with later birth years. The highest risk of incidence was observed in the 1955-1959 birth cohort (RR=1.788, 95%CI: 1.699-1.881). In contrast, the risks of mortality and disability exhibited relatively stable trends overall. Conclusions The disease burden of oral cancer among the Chinese elderly generally exhibited an increasing trend from 1992 to 2021, with particularly high burden observed among the elderly aged 85-<90 years. The incidence risk increased with time and year of birth.

Objective: To analyze the mediating effect of activities of daily living (ADL) among patients with chronic obstructive pulmonary disease (COPD) on caregiver ability and caregiver burden, so as to provide a basis for improving the quality of care. Methods: From February 2024 to March 2025, COPD patients and their caregivers from the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in Haikou were selected using convenience sampling method. Data on the basic characteristics of both caregivers and patients were collected through questionnaire surveys. The Chinese version of the Family Caregiver Capacity Scale, the Chinese version of the Caregiver Burden Inventory, and the Barthel Index were used to assess caregiver ability, caregiver burden, and patients' ADL, respectively. The mediating effect of ADL among COPD patients on caregiver ability and caregiver burden was analyzed using the Process macro 4.0, with the significance tested via the Bootstrap method. Results: A total of 348 caregivers were surveyed, among whom 274 (78.74%) were females and 74 (21.26%) were males. The majority of caregivers were aged 40 years and above, with 291 individuals (83.62%). The relationship between caregivers and patients was primarily that of being their children, with 185 individuals (53.16%). Correspondingly, 348 COPD patients were surveyed, and the predominant type of medical insurance was the New Rural Cooperative Medical Scheme, with 172 cases (49.43%). The median scores of caregiver ability, caregiver burden, and patients' ADL were 19.00 (interquartile range, 5.00), 47.00 (interquartile range, 8.00) and 45.00 (interquartile range, 15.00) points, respectively. Mediating analysis showed that caregiver ability directly affected caregiver burden, with an effect value of 0.693 (95%CI: 0.553-0.832). It also indirectly affected caregiver burden through the patients' ADL, with an effect value of 0.104 (95%CI: 0.029-0.179). This mediating effect accounted for 13.05% of the total effect. Conclusion The ADL of COPD patients played a mediating role between caregiver ability and caregiver burden, with caregiver ability exerting a significant positive indirect effect on caregiver burden through patients' ADL.