ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease （AD） through regulating mitochondrial Ca²⁺ homeostasis and kinetic balance based on the protein kinase A （PKA）/calcineurin （CaN） signaling pathway. MethodsSixty three-month-old amyloid precursor protein （APP）/presenilin 1 （PS1） double transgenic mice were randomly divided into a model group， a donepezil group（0.65 mg·kg^-1）， a low-dose Yizhi Qingxin prescription group （YQF-L，2.6 g·kg^-1）， a medium-dose Yizhi Qingxin prescription group （YQF-M，5.2 g·kg^-1）， and a high-dose Yizhi Qingxin prescription group （YQF-H，10.4 g·kg^-1）， with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily， with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition （NOR） and Morris water maze （MWM） tests. Hematoxylin-eosin （HE）/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy （TEM） was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester （Fluo-4 AM） Ca²⁺ probe was used to measure intracellular Ca²⁺ concentration in brain tissue. Western blot was used to determine the protein expression of PKA， CaN， sodium/calcium/lithium exchanger （NCLX）， mitochondrial calcium uniporter （MCU）， calmodulin （CaM）， dynamin-related protein 1 （Drp1）， and phosphorylated dynamin-related protein 1 （serine 637 site） ［p-Drp1（S637）］ in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the expression of PKA， CaN， CaM， NCLX， MCU， and Drp1 mRNAs. ResultsCompared with those in the normal group， the recognition index （RI） of the model group decreased （P0.01）， and the number of crossings through the original platform area， the duration of stay in the target quadrant， and the distance were reduced （P0.01）. The protein expression of PKA， NCLX， and p-DRP1 （ser637） significantly decreased （P0.05）， and the mRNA expression of PKA and NCLX significantly decreased （P0.05）. The escape latency （EL） was prolonged （P0.05）， and the intracellular Ca²⁺ level significantly increased （P0.01）. The protein expression of CaN， CaM， MCU， and Drp1， as well as the mRNA expression of CaN， MCU， and Drp1， significantly increased （P0.05）. After intervention with Donepezil and Yizhi Qingxin prescription， compared with that in the model group， the RI of the treatment group significantly increased （P0.05）， and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased （P0.05）. The protein expression of PKA， NCLX， and p-Drp1 （ser637） and the mRNA expression of PKA and NCLX significantly increased （P0.05）. On the 4th and 5th days， the EL was shortened （P0.05）， and the intracellular Ca²⁺ level decreased （P0.05）. The protein expression of CaN， CaM， MCU， and Drp1 and the mRNA expression of CaN， MCU， and Drp1 significantly decreased （P0.05）. ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway， upregulates the expression of PKA， NCLX， and p-Drp1 （ser637） proteins， reduces the expression of CaN， CaM， MCU， and Drp1 proteins， and regulates Ca²⁺ homeostasis and mitochondrial dynamic balance， thereby enhancing the spatial learning and memory abilities of AD mice.

ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease （AD） through regulating mitochondrial Ca²⁺ homeostasis and kinetic balance based on the protein kinase A （PKA）/calcineurin （CaN） signaling pathway. MethodsSixty three-month-old amyloid precursor protein （APP）/presenilin 1 （PS1） double transgenic mice were randomly divided into a model group， a donepezil group（0.65 mg·kg^-1）， a low-dose Yizhi Qingxin prescription group （YQF-L，2.6 g·kg^-1）， a medium-dose Yizhi Qingxin prescription group （YQF-M，5.2 g·kg^-1）， and a high-dose Yizhi Qingxin prescription group （YQF-H，10.4 g·kg^-1）， with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily， with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition （NOR） and Morris water maze （MWM） tests. Hematoxylin-eosin （HE）/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy （TEM） was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester （Fluo-4 AM） Ca²⁺ probe was used to measure intracellular Ca²⁺ concentration in brain tissue. Western blot was used to determine the protein expression of PKA， CaN， sodium/calcium/lithium exchanger （NCLX）， mitochondrial calcium uniporter （MCU）， calmodulin （CaM）， dynamin-related protein 1 （Drp1）， and phosphorylated dynamin-related protein 1 （serine 637 site） ［p-Drp1（S637）］ in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the expression of PKA， CaN， CaM， NCLX， MCU， and Drp1 mRNAs. ResultsCompared with those in the normal group， the recognition index （RI） of the model group decreased （P0.01）， and the number of crossings through the original platform area， the duration of stay in the target quadrant， and the distance were reduced （P0.01）. The protein expression of PKA， NCLX， and p-DRP1 （ser637） significantly decreased （P0.05）， and the mRNA expression of PKA and NCLX significantly decreased （P0.05）. The escape latency （EL） was prolonged （P0.05）， and the intracellular Ca²⁺ level significantly increased （P0.01）. The protein expression of CaN， CaM， MCU， and Drp1， as well as the mRNA expression of CaN， MCU， and Drp1， significantly increased （P0.05）. After intervention with Donepezil and Yizhi Qingxin prescription， compared with that in the model group， the RI of the treatment group significantly increased （P0.05）， and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased （P0.05）. The protein expression of PKA， NCLX， and p-Drp1 （ser637） and the mRNA expression of PKA and NCLX significantly increased （P0.05）. On the 4th and 5th days， the EL was shortened （P0.05）， and the intracellular Ca²⁺ level decreased （P0.05）. The protein expression of CaN， CaM， MCU， and Drp1 and the mRNA expression of CaN， MCU， and Drp1 significantly decreased （P0.05）. ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway， upregulates the expression of PKA， NCLX， and p-Drp1 （ser637） proteins， reduces the expression of CaN， CaM， MCU， and Drp1 proteins， and regulates Ca²⁺ homeostasis and mitochondrial dynamic balance， thereby enhancing the spatial learning and memory abilities of AD mice.

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

Objective To evaluate the efficacy of modified cardiac rehabilitation combined with Xuefu Zhuyu decoction on patients with heart failure of Qi deficiency and blood stasis type,with a focus on analyzing the improvement of galectin-3(Gal-3),soluble suppression of tumorigenicity 2(sST2)levels,cardiac function,traditional Chinese medicine syndromes,and exercise tolerance.Methods 180 patients with heart failure of Qi deficiency and blood stasis type who attended the Department of Rehabilitation Medicine,Huzhou First People's Hospital from October 2021 to March 2023 were selected and randomly divided into treatment group(modified cardiac rehabilitation+Xuefu Zhuyu decoction)and control group(conventional treatment),with a treatment course of 12 weeks.The changes of Gal-3,sST2,left ventricular ejection fraction(LVEF),New York heart association functional classification(NYHA),N-terminal B-type natriuretic peptide(NT-proBNP),traditional Chinese medicine syndrome score and 6-minute walk test(6MWT)were compared between two groups before and after 12 weeks of treatment,and the safety was evaluated.Results After 12 weeks of treatment,Gal-3 and sST2 levels of patients in treatment group were significantly lower than those in control group;LVEF levels of patients in treatment group were significantly higher than those in control group,and the degree of improvement of cardiac function grading in treatment group was significantly better than that in control group;NT-proBNP in treatment group was significantly lower than that in control group;The 6MWT in treatment group was significantly higher than that in control group;The score of traditional Chinese medicine syndrome in treatment group was lower than that in control group;The difference is statistically significant(P＜0.05).After 12 weeks of treatment,the effective rate of treatment group was significantly higher than that of control group(P＜0.05);There was no statistically significant difference in adverse reactions and serious adverse events between two groups of patients(P＞0.05).Conclusion Modified cardiac rehabilitation combined with Xuefu Zhuyu decoction can significantly improve cardiac function,traditional Chinese symptoms,and exercise tolerance in patients with heart failure of Qi deficiency and blood stasis type,reduce Gal-3 and sST2 levels,and has high clinical application value.

Objective To observe the alterations of protein expression of nicotinamide adenine di-nucleotide phosphatase oxidase 4-silent mating type information regulation 2 homolog 1(NOX4-SIRT1)signaling pathway in ApoE-/-mice and C57BL/6J mice induced by high-fat diet.Methods Twenty ApoE-/-mice and 40 C57BL/6J mice,aged of 10 weeks and half male and half female,were randomly divided into a NC group and a HFD group,with 10 mice in each group(ApoE-/-+NC and ApoE-/-+HFD groups,and C57+NC and C57+HFD groups).After 1 week of adaptive feed-ing period,each group was fed with their corresponding diet for subsequent 12 weeks,and then blood samples were collected from the anesthetized orbits and aortic arch tissues were harvested.HE staining and Masson staining were performed to examine the pathological morphology of the aortic arch tissues.The serum levels of TG,TC,HDL-C and LDL-C were measured using an auto-matic biochemical analyzer.The content of ox-LDLC was detected with ELISA,and the contents of ROS,GSH,GPX and NAD+were measured by colorimetry.The expression of SIRT1,p53,p21 and NOX4 was detected by Western blotting.Results Compared with the C57+NC group,the ApoE-/-+NC group showed significant lipid deposition,increased collagen fibers,elevated levels of TC,TG,HDLC,LDL-C,ox-LDL-C and ROS and increased p21 expression level,and obviously decreased contents of GSH,GPX and NAD+(P＜0.05,P＜0.01).Compared with the ApoE-/-+NC group,the ApoE-/-+HFD group showed larger plaque areas,lessened elastic fibers,more col-lagen fibers,increased levels of TC,HDL-C,LDL-C,ox-LDL-C and ROS,and p21 expression level(P＜0.01),and declined expression of GSH,GPX,NAD+and NOX4[6.4±0.8 μmol/L vs 9.6±0.8 μmol/L,242.0±39.0 U/ml vs 362.7±11.1 U/ml,0.61±0.15 nmol/L vs 1.07±0.20 nmol/L,0.26±0.01 vs 0.32±0.03;P＜0.05,P＜0.01[.Conclusion High-fat diet may accelerate vascular aging by elevating lipid and oxidative stress levels,decreasing NAD+and NOX4 expression,ele-vating p21 expression,and thereby activating the NOX4-SIRT1 pathway.

OBJECTIVE To investigate the mechanism of baicalin in alleviating the intestinal mucosal barrier injury in rats with intraperitoneal infection-induced sepsis through the vitamin D receptor(VDR)/nuclear factor E2-relat-ed factor 2(Nrf2)/haemoglobin oxygenase-1(HO-1)signalling pathway.METHODS Twenty-four SD rats were randomly divided into a sham-surgery group,a model group,an ulinastatin group and a baicalin group,with six rats in each group.Sepsis models were established via cecal ligation and puncture(CLP)in rats in each groups ex-cept for the sham surgery group.Six hours after modeling,the sham-surgery and the model groups received intra-peritoneal saline,while the ulinastatin and baicalin groups were administered ulinastatin at 20,000 U/kg and ba-icalin at 100 mg/kg,respectively,via intraperitoneal injection once daily for 5 consecutive days.The histopatho-logical changes in the ileum tissue of rats in each group were observed,and the levels of oxidative stress,inflam-matory factors,and the expression of related mRNA and proteins in the VDR/Nrf2/HO-1 signalling pathway were compared.RESULTS Compared with the sham-surgery group,the model group showed disordered villus ar-rangement,severe intestinal mucosal atrophy and inflammatory cell infiltration,with necrotic epithelial cell shed-ding.Additionally,in the model group,the total antioxidant capacity(T-AOC),superoxide dismutase(SOD),and glutathione peroxidase(GSH-PX)levels reduced,while the levels of tumor necrosis factor-α(TNF-α),inter-leukin(IL)-6,and IL-1βsignificantly increased,and the expression of VDR mRNA,Nrf2 mRNA,HO-1 mR-NA,and VDR,Nrf2,and HO-1 proteins were downregulated(P<0.05).Compared with the model group,the ulinastatin group and the baicalin group showed that villus arrangement,intestinal mucosal atrophy and inflamma-tory cell infiltration got improved,the levels of T-AOC,SOD,and GSH-PX elevated,the levels of TNF-α,IL-6,and IL-1βdecreased,and expressions of VDR mRNA,Nrf2 mRNA,HO-1 mRNA,and VDR,Nrf2,and HO-1 proteins were upregulated.Moreover,all indicators in the baicalin group were superior to those in the ulinastatin group(P<0.05).CONCLUSION Baicalin can inhibit the expression of inflammatory factors and regulate the bal-ance of oxidative stress in vivo by up-regulating the VDR/Nrf2/HO-1 signaling pathway,thereby alleviate the in-testinal mucosal barrier dysfunction caused by intraperitoneal infection-induced sepsis.

Objective To investigate the relationship between serum amyloid A(SAA),interleukin-10(IL-10),interleukin-21(IL-21)levels and the first acute exacerbation in patients with chronic obstructive pulmo-nary disease(COPD)with pneumothorax.Methods A total of 102 patients with stable COPD complicated with pneumothorax admitted to the hospital from January 2020 to January 2023 were selected.They were treated with closed thoracic drainage,anti-inflammatory,antiasthmatic,expectorant,and high-flow nasal hu-midification oxygen therapy(HFNC).The patients were divided into two groups according to whether they had the first acute exacerbation within 1 year after treatment,the first acute exacerbation group(32 patients had the first acute exacerbation within 1 year of follow-up)and the non-first acute exacerbation group(70 pa-tients had no first acute exacerbation within 1 year of follow-up).Serum SAA,IL-10 and IL-21 levels and blood gas indexes were compared between the two groups after treatment.Multivariate Logistic regression a-nalysis was used to analyze the influencing factors of the first acute exacerbation after HFNC treatment.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum SAA,IL-10 and IL-21 levels after treatment for the first acute exacerbation of COPD patients with pneumothorax.Results There were significant differences in hypoproteinemia,smoking,underlying diseases,forced vital ca-pacity(FVC),forced expiratory volume in one second(FEV1)as a percentage of predicted value(FEV1%),FEV1 to FVC ratio(FEV1/FVC),arterial partial pressure of oxygen(PaO2),arterial partial pressure of car-bon dioxide(PaCO2),SAA,IL-10,IL-21 between the two groups(P<0.05).Multivariate Logistic regression analysis showed that hypoproteinemia,smoking,underlying diseases,PaCO2,SAA,IL-10 and IL-21 were the risk factors for the first acute exacerbation after HFNC treatment(P<0.05).FVC,FEV1%,FEV1/FVC and PaO2 were protective factors for the first acute exacerbation after treatment(P<0.05).ROC curve results showed that the area under the curve(AUC)of SAA,IL-10 and IL-21 levels after treatment to predict the first acute exacerbation of COPD patients with pneumothorax was 0.755,0.726 and 0.674,respectively.When the cut-off values of SAA,IL-10 and IL-21 were 171.06 g/L,26.46 pg/mL and 244.79 pg/mL,the sen-sitivity was 76.51%,60.84%and 56.90%,and the specificity was 66.73%,74.49%and 74.52%,respective-ly.The AUC of combined prediction was 0.860,the sensitivity was 80.44%,and the specificity was 76.51%.Conclusion The serum SAA,IL-10 and IL-21 levels in COPD patients with pneumothorax have certain pre-dictive value for the first acute exacerbation of COPD patients with pneumothorax.

Objective To explore the clinical effect of quality control circle(QCC)activities on the prevention of postoperative deep vein thrombosis(DVT)in inpatients in military hospitals.Methods A total of 318 patients who were diagnosed and treated in The First Affiliated Hospital of Air Force Medical University from January to December 2021 and 40 medical staff were enrolled in this study.Routine care was performed in 158 patients from January to June 2021,and QCC care was implemented in 160 patients from July to December 2021.The awareness of DVT prevention in medical staff and patients(or their famiy members)before and after QCC activities,lower limb DVT preventive measures taken by medical staff,and the occurrence of DVT were compared.Results The scores of the cause,clinical manifestations,nursing measures and preventive measures of DVT after QCC activities were significantly higher than those before QCC activities in both medical staff and patients(or their families)(P<0.05).The overall implementation rate of preventing lower limb DVT after QCC activities was significantly higher than that before QCC activities(94.14%vs.46.20%,P<0.05).The incidence of DVT after QCC activities was significantly lower than that before QCC activities(0.62%vs.5.06%,P<0.05).Conclusion Implementing QCC activities can improve the cognitive ability of military medical staff and patients(or family members)in DVT prevention,increase the implementation rate of DVT prevention measures,and reduce the incidence of DVT.

ObjectiveTo introduce the three main techniques for tuberculosis screening currently used in China, to systematically evaluate their accuracy in diagnosing latent tuberculosis infection (LTBI), so as to provide scientific basis and recommendations for the formulation of China’s tuberculosis screening strategy. MethodsLiterature on the diagnosis of tuberculosis by tuberculin skin test (TST), interferon-γ release assay (IGRA), and recombinant Mycobacterium tuberculosis fusion protein (EC) skin test from January 1, 2010 to August 22, 2024 was comprehensively retrieved from PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Database through computerized search. Besides, all the literature was screened in accordance to the inclusion criteria for diagnostic tests, and characteristic information of the literature selected was extracted simultaneously. Meta-analysis was performed using Stata 17.0 software, with a random-effects model used for weighted quantitative synthesis of included literature, calculating pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and their 95% confidence intervals (CI). ResultsA total of 543 relevant articles were retrieved, with 105 ultimately included. Among them, 33 articles reported diagnostic data for TST, with a pooled sensitivity of 0.68 (95%CI: 0.62‒0.73), specificity of 0.67 (95%CI: 0.60‒0.73), positive likelihood ratio of 2.0 (95%CI: 1.7‒2.5), and negative likelihood ratio of 0.48 (95%CI: 0.40‒0.58). Ninety-four articles reported the diagnostic value of IGRAs test, with a pooled sensitivity of 0.88 (95%CI: 0.87‒0.89), specificity of 0.82 (95%CI: 0.79‒0.84), positive likelihood ratio of 4.8 (95%CI: 4.2‒5.6), and negative likelihood ratio of 0.15 (95%CI: 0.13‒0.17). Data on EC skin test was limited, but preliminary analysis showed that it had high sensitivity and specificity. ConclusionIGRA has a significant advantage in diagnosing LTBI, and EC skin test also shows good diagnostic performance, although relevant data is limited. TST remains suitable for large-scale screening due to its cost-effectiveness.

The core idea of occupational health risk assessment models is to systematically evaluate occupational health risks according to target hazard characteristics and relevant exposure levels of workers. Occupational exposure assessment is based on concentration, frequency, exposure time, and other indicators that indicate actual exposure of workers to occupational hazards, which is a critical component of health risk assessment. However, the accuracy and comparability of assessment results are affected by differences in parameter assignment for exposure assessment across different studies, as well as insufficient emphasis on multiple occupational hazard exposure. This review aimed to explore the assignment and standardization of exposure assessment parameters for occupational health risk assessment modeling, and systematically sorted out the meaning, assignment methods, and sources of exposure assessment related parameters in commonly used occupational health risk assessment models, with the goal of providing researchers with standardized assessment tools to enhance the scientific rigor and practicality of occupational health risk assessments. Considering the individual differences and temporal fluctuations in occupational exposure, it is recommended that researchers should adopt appropriate sampling strategies, reasonably select sample subjects and time based on the division of similar exposure group (SEG), and conduct statistical inference on the obtained data to derive representative exposure parameters. For combined exposure to chemicals with similar toxic effects, the health risk assessment methods are relatively mature. However, the assessment of combined exposure to hazards with different properties and health effects still lacks scientific authority and needs further research and discussion.