This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

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

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

Objective To explore the effects of evidence-based nursing combined with multi-dimensional health education on negative emotions and postoperative rehabilitation of patients undergoing elective surgery for cholecystolithiasis.Methods A total of 100 patients with cholecystolithiasis who underwent elective surgery in Yixing Traditional Chinese Hospital Medicine from September 2023 to August 2024 were selected.The patients were assigned to control group and observation group by PEMS3.1 for Windows completely random(two groups and multiple groups)program,with 50 cases in each group.The control group received routine nursing,and the observation group received evidence-based nursing combined with multidimensional health education on the basis of routine nursing.The intervention duration of the two groups was 7 days.Visual analogue scale(VAS)scores,negative emotions(self-rating anxiety scale[SAS]and self-rating depression scale[SDS]),postoperative complications,and postoperative rehabilitation were compared between the two groups.Results The VAS scores at 24 h and 72 h after surgery were lower than those at 6 h after surgery in both groups,especially in the observation group(P<0.05).The scores of SAS and SDS in both groups after intervention were significantly decreased compared with those before intervention,and the scores of negative emotions in the observation group after intervention were significantly lower than those in the control group(P<0.05).The total incidence of gastrointestinal discomfort,biliary fistula and wound infection/bleeding in the observation group was significantly lower than that in the control group(4.00%vs.18.00%,P<0.05).The time of getting out of bed,the time of anal exhaust,the time of resuming normal diet and the time of hospitalization in the observation group were significantly lower than those in the control group(P<0.05).Conclusion The combination of evidence-based nursing and multi-dimensional health education during perioperative period of cholecystolithiasis surgery can reduce postoperative pain,improve the positive attitude of treatment,reduce complications,and promote the recovery of the disease.

Atherosclerosis(AS)is an inflammatory cardiovascular disease characterized by plaque accumulation in the arterial wall,leading to increased morbidity and mortality of related cardiovascular disorders.The main pathological mechanisms of AS include lipid deposition,oxidative stress,and chronic inflammation,with disease progression involving endothelial cell dysfunction,macrophage polarization,foam cell formation,and smooth muscle cell proliferation or apoptosis.Mitochondria are essential organelles that provide energy for cellular metabolism,and the mitochondrial quality control(MQC)system is the fundamental mechanism maintaining mitochondrial functional homeostasis.MQC dysfunction can induce vascular phenotype changes through pathways such as oxidative stress,apoptosis,and inflammation,thereby promoting the progression of AS.Therefore,targeting MQC to regulate mitochondrial function may become a new direction for the treatment of AS.This review summarizes the molecular mechanisms of MQC,including mitochondrial biogenesis,mitochondrial dynamics,and mitochondrial autophagy(mitophagy),and further elucidates the role of abnormal MQC in the pathological processes of AS,aiming to provide a scientific basis for identifying potential targets to delay the progression of AS and developing related drugs.

OBJECTIVE To observe the causal association between colorectal cancer and sepsis by means of bidirec-tional two-sample Mendelian randomization(MR).METHODS The Genome Wide Association Study(GWAS)datasets for colorectal cancer and sepsis were retrieved from the GWAS databases between its establishment and Feb.1,2024.MR was carried out for the colorectal cancer and sepsis interacting as exposure and outcome factors.The single nucleotide polymorhpism(SNPs)that were significantly associated with the exposure factors were screened out by setting P as less than 5.0× 10-8,r2 less than 0.001,the genetic distance 10,000 kb.The SNPs that were remarkably associated with the exposure factors were extracted from the GWAS datasets of the outcome variables,the instrumental variable were finally obtained,the inverse variance weighting(IVW)was taken as the main approach for the causal inference.The level pleiotropy was tested by using MR Egger method and MR-PRESSO,the heterogeneity was tested by IVW method and MR-Egger method,the sensitivity was analyzed by leave-one-out method,and the robustness of the result was tested.RESULTS A total of 30 SNPs were screed out by setting the colorectal cancer as exposure factor and the sepsis as outcome variable(F＞10);there was causal as-sociation between the colorectal cancer and the sepsis(OR=28.955,95％CI:1.215 to 690.052,P=0.037).Totally 14 SNPs were screened out by setting the sepsis as exposure factor and the colorectal cancer as treatment variable(F＞10),and there was no causal association between the colorectal cancer and the sepsis(OR=0.999,95％CI:0.997 to 1.002,P=0.674).There was no level pleiotropy in the instrumental variables during the two times of MR analysis;there was no heterogeneity in the instrumental variables,and the result of the MR analysis was robust.CONCLUSION There is causal association between the colorectal cancer and the increases of risk of sepsis.But there is no causal association between the sepsis and the increase of risk of colorectal cancer.

Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.

Aim To investigate the protective effect of Siwu decoction(SWD)on immune injury induced by 60Coγ-rays in mice and the related mechanism.Meth-ods C57BL/6J mice were randomly divided into six groups:Control group(Control),Model group(Mod-el),Siwu decoction low-dose group(SWD-L),Siwu decoction medium-dose group(SWD-M),Siwu decoc-tion high-dose group(SWD-H)and resveratrol positive group(Resveratrol,Res).The drug was continued to be administered 11 days before and after irradiation,with a single whole-body irradiation of 4 Gy,and all in-dexes were detected three days after irradiation.The changes of peripheral blood and organ indexes were de-tected.Serum levels of cytokine interferon gamma(IFN-γ),interleukin-1 β(IL-1 β),IL-2,IL-4,IL-6,IL-10,IL-17,transforming growth factor-β(TGF-β),tumor necrosis factor(TNF)-α,and immunoglobulin A(IgA),IgG,IgM,and complement protein 3(C3),C4 content were detected by enzyme-linked immunosorbent assay(ELISA).B lymphocytes,T lymphocytes,NK cells in spleen and T lymphocytes in thymus were de-tected by flow cytometry.The pathological changes of spleen and thymus were analyzed by hematoxylin-eosin(HE)staining.The expression of Sirt 1 protein in spleen after radiation was detected by immunofluores-cence staining.The protein contents of Sirt1,PI3K,Akt,p-Akt and mTOR in spleen were detected by Western blot assay.Results SWD could significantly increase LYMPH％and reduce pathological injury of spleen and thymus.Flow cytometry showed that SWD could significantly increase the percentage of CD19+B lymphocytes in spleen,decrease the percentage of NK lymphocytes and the ratio of CD4+/CD8+in spleen and thymus.ELISA results showed that SWD signifi-cantly inhibited the expression of IL-1 β,IL-2,IL-6,IL-17,IFN-γ,TGF-β,TNF-α,and increased the content of anti-inflammatory factors IL-4 and IL-10.At the same time,SWD significantly inhibited the increase of IgA,IgG,IgM,C3 and C4 induced by radiation.The results of immunofluorescence staining and Western blot showed that SWD could decrease the expression of PI3K,Akt,p-Akt and mTOR protein,and enhance the expression of Sirt1 protein.Conclusions SWD has obvious preventive effect on immune damage induced by 60Co gamma radiation in mice.The mechanism may be related to Sirt1-PI3K-Akt-mTOR.

Objective A new occipital bone removal technology was applied to improve the success rate of brain removal.Methods The skull was sawed based on the traditional brain removal technology,and part of the occipital bone was removed downward centered in external occipital protuberance to the foramen magnum,then exposed the telencephalon,cerebellum and posterior medulla oblongata.After that,removed the tentorium cerebelli and cut down the medulla oblongata and the related cranial nerves at the skull base,then removed the brain tissues.Results The removed brain tissues had structurally intact telencephalon,cerebellum and brain stem,clear vessels in the cerebral sulci,and relatively intact optic chiasm,olfactory tracts and vertebro-basilar arteries.Conclusion Brain removal through a fenestration on the external occipital protuberance can effectively preserve the integrity of brain specimens,and improve the success rate of brain removal,which is of great significance for central nervous system teaching and improvement of human brain tissue repositories.