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.

Objective To obtain the protective performance parameters of barium sulfate mortar against positron nuclide γ-rays, provide reference data for precise shielding calculations, and guide the design, evaluation, and construction of radiation shielding. Methods The FLUKA program was used to build a model for simulating the dose equivalent rate variation around points of interest under the irradiation of the most commonly used positron nuclide ¹⁸F with changes in the thicknesses of lead and barium sulfate mortar. The transmission curves of lead and barium sulfate mortar were fitted, and the half-value layer (HVL) and lead equivalence of barium sulfate mortar were calculated based on the fitted curves. Results The ambient dose equivalent rate coefficient of positron nuclide ¹⁸F was 1.339 4×10⁻¹ μSv·m²/MBq·h and the HVL for lead was 4.037 mm, with deviations of 0.043% and 1.53% compared to the values provided in the AAPM Report No. 108, respectively. The HVLs for γ-rays produced by ¹⁸F, using barium sulfate mortar with apparent densities of 4.20, 4.00, and 3.90 g/cm³ mixed with 35.2-grade cement in a 4∶1 mass ratio, were 2.914, 2.969, and 3.079 cm, respectively. The lead equivalences were 0.1385, 0.1360, and 0.1311 mmPb/mm, respectively. Conclusion The three types of barium sulfate mortar can provide good protection against γ-rays in positron imaging locations. As the apparent density of barium sulfate increases, its protective effect improves slightly but remains significantly better than common construction materials like concrete and solid bricks.

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.

Objective:To explore the correlation between Chinese visceral adiposity index (CVAI) and metabolic associated fatty liver disease (MAFLD) so as to evaluate its predictive value for MAFLD.Methods:Six hundred and thirteen cases admitted to the Department of Gastroenterology, Zhongshan Hospital Affiliated to Dalian University from June 2022 to August 2023 were selected and divided into the MAFLD group ( n=312) and the non-MAFLD group ( n=301) according to the diagnostic criteria of MAFLD. The clinical data differences between the two groups were compared. The MAFLD group was divided into a mild MAFLD group ( n=243) and a moderate to severe MAFLD group ( n=69) according to the liver/spleen CT value. The differences in body fat indices such as CVAI, visceral fat index (VAI), and visceral fat area (VFA) were compared between subjects with different degrees of MAFLD. The Spearman test was used to analyze the correlation between CVAI, VAI, and various clinical indicators. The subjects were divided into groups (Q1-Q4) according to the quartile levels of CVAI and VAI, and the distribution of MAFLD conditions among the groups was compared. Logistic regression analysis was used to determine the occurrence risk of MAFLD at different CVAI and VAI levels. The receiver operating characteristic curve was drawn. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the predictive value of CVAI, VAI, VFA, waist circumference, and body mass index for MAFLD. The DeLong test was used to compare the differences in the AUC of each predictive index. Results:The prevalence of hypertension and type 2 diabetes mellitus, and the levels of systolic blood pressure, diastolic blood pressure, CVAI, VAI, VFA, subcutaneous fat area, waist circumference, body mass index, total cholesterol, triglycerides, low-density lipoprotein cholesterol, fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, and serum uric acid were higher in the MAFLD group than the non-MAFLD group ( P<0.05), while the level of high-density lipoprotein cholesterol was lower than the non-MAFLD group ( P<0.001). The levels of CVAI, VAI, VFA, waist circumference, and body mass index were higher in the mild and the moderate to severe MAFLD group than those in the non-MAFLD group ( P<0.001). The detection rate of MAFLD gradually increased( χ2=176.953, 133.659, P<0.001) with the increase of CVAI and VAI levels. Correlation analysis showed that CVAI was positively correlated with VFA ( r=0.755, P<0.001) and the homeostasis model assessment of insulin resistance ( r=0.579, P<0.001). Multivariate logistic regression analysis showed that after adjusting for various risk factors, the risk of MAFLD in the Q4 group of the CVAI subgroup was still 7.159 times that of the Q1 group (95% CI:3.126-16.392, P<0.001), and the risk of MAFLD in the Q4 group of the VAI subgroup was still 4.667 times that of the Q1 group (95% CI: 2.187-9.962, P<0.001). The receiver operating characteristic curve results showed that the AUC of CVAI for predicting MAFLD was similar to that of VFA (0.822 vs. 0.826), and higher than that of VAI (AUC 0.772), waist circumference (AUC 0.796), and body mass index (AUC 0.755). The optimal critical value of CVAI for predicting the risk of MAFLD was 125.50, with sensitivity and specificity at 70.5% and 79.1%, respectively. Conclusion:The patient's risk of MAFLD increases with the rise of CVAI level, and CVAI has a favorable predictive value for the occurrence of MAFLD.

Liver diseases have a high prevalence rate worldwide with relatively poor long-term clinical outcomes and have become one of the leading causes of disease burden and death around the world,which poses significant challenges to public health.Eosinophils(Eos)are a class of highly conserved multifunctional immune cells that play critical effector roles in allergic diseases.In recent years,an increasing amount of evidence has shown that Eos plays an important role in the pathogenesis of liver diseases,exerting a protective or harmful effect in different liver diseases,which has become a research hotspot in this field.This article elaborates on the role and potential mechanism of action of Eos in liver diseases,in order to provide a new perspective for in-depth research on the pathogenesis of liver diseases and lay the foundation for developing therapeutic strategies targeting Eos.

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

Liver diseases have a high prevalence rate worldwide with relatively poor long-term clinical outcomes and have become one of the leading causes of disease burden and death around the world,which poses significant challenges to public health.Eosinophils(Eos)are a class of highly conserved multifunctional immune cells that play critical effector roles in allergic diseases.In recent years,an increasing amount of evidence has shown that Eos plays an important role in the pathogenesis of liver diseases,exerting a protective or harmful effect in different liver diseases,which has become a research hotspot in this field.This article elaborates on the role and potential mechanism of action of Eos in liver diseases,in order to provide a new perspective for in-depth research on the pathogenesis of liver diseases and lay the foundation for developing therapeutic strategies targeting Eos.

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.