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.

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 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.

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 simulate and analyze the dose distribution from external exposure and its influencing factors of induced radioactivity in proton therapy site. Methods Referencing a domestically under-construction proton therapy facility, a geometric model of the proton therapy site was constructed, and the FLUKA program was used to simulate the distribution of the induced radioactive dose of the proton therapy site under the conditions of different energies, beam angles, irradiation time, cooling time and medium of the treatment site. Results For a 230 MeV proton beam with a current of 3.0 nA, directed along the negative Z-axis and irradiating a phantom for two minutes, at the shutdown moment, the ambient dose equivalent rates in air and vacuum 5, 30, and 50 cm away from the phantom surface were (1 039.02±5.82)-(127.86±1.20) and (1 037.96±4.38)~(127.35±0.93) μSv/h, respectively. The mean difference was 0.51~1.06 μSv/h, and the air-immersed external irradiation accounted for <1% of the total irradiation, which rapidly decreased to 1/15 of the shutdown moment value after cooling for 10 minutes. Under the condition of 130~250 MeV, the ambient dose equivalent rates at the shutdown moments 5, 30 and 50 cm away from the surface of the phantom were (427.49±3.12)-(1 058.41±4.66), (100.36±0.92)-(259.70±1.69) and (50.15±0.68)-(131.93±1.11) μSv/h, respectively. Irradiation for one-five minutes, and at the moment of shutdown at 5, 30, and 50 cm from the surface of the phantom were (688.19±3.33)-(1 594.04±8.08), (167.60±1.35)-(388.24±2.96) and (84.73±0.69)-(195.94±1.56) μSv/h. The peripheral dose-equivalent rate of the sensed radioactivity decreases with the irradiation time, the energy of the beam, and the distance from the model. The peak dose equivalent rate around the induced radioactivity exists in the beam direction, which is significantly larger than that in the non-beam direction. Conclusion Proton therapy sites are characterized by relatively large levels of induced peripheral radioactive dose equivalent rates, mainly originating from patients. In actual practice, a suitable working position can be chosen according to the direction of the beam current, especially the direction of the final irradiation field beam current, in the non-beam current direction and as far away from the patient as possible. Within 10 minutes after the end of treatment, staff should try to avoid close contact with the patients.

As an important non-drug treatment for chronic obstructive pulmonary disease(COPD),pulmonary rehabilitation helps to improve dyspnea and negative emotions.This article mainly elaborates on pulmonary rehabilitation contents such as smoking cessation,breathing training,exercise training,traditional Chinese medicine rehabilitation,and psychological rehabilitation,and discusses the application of telemedicine and virtual reality technology in COPD pulmonary rehabilitation.The COVID-19 has a certain impact on the traditional pulmonary rehabilitation model.This article explores the relationship between COVID-19 and COPD and the implementation methods of pulmonary rehabilitation for COPD patients with COVID-19,so as to provide evidence-based basis for the implementation of pulmonary rehabilitation in the context of COVID-19,and provide new ideas and methods for improving the clinical treatment effect of COPD.

Objective:To establish a risk management system of bedside monitor based on risk assessment management model,and to analyze its application value in the clinical management of critically ill patients in neurosurgery department.Methods:Based on the risk assessment management model,the failure risk index was screened,and the risk management system of bedside monitor was established.A total of 150 critically ill neurosurgical patients admitted to The First Affiliated Hospital of Air Force Medical University from December 2021 to December 2022 were selected and divided into control group and observation group by random number table method,with 75 cases in each group.During the hospitalization of the two groups of patients,30 responsible nurses participated in clinical care,and 16 multifunctional bedside monitors were used to monitor patients'vital signs.The control group received routine nursing management intervention.On the basis of routine nursing intervention,the observation group carried out risk assessment management based on the risk assessment management model of bedside monitor risk management system.The differences in patient monitoring quality score,equipment management quality score and responsible nurse ability score were compared between the two groups.Results:The average scores of respiration,blood pressure,blood oxygen saturation and ECG monitoring quality of the patients in observation group were(37.52±0.26)points,(36.61±1.29)points,(36.56±2.57)points and(38.25±0.56)points,respectively,which were higher than those in control group,the difference was statistically significant(t=43.925,33.150,13.655,32.035,P<0.05).The average scores of performance control quality and operation quality of bedside monitor in the observation group were(95.43±0.46)points and(96.51±0.77)points,respectively,which were higher than those in control group,the difference was statistically significant(t=70.976,35.439,P<0.05).The average scores of nurses in terms of ability of equipment collaboration,equipment use mastery and equipment alarm management in the observation group were(9.43±0.25)points,(8.56±0.64)points and(9.25±0.24)points,respectively,which were higher than those in the control group,the differences were statistically significant(t=92.952,24.455,58.024,P<0.05).Conclusion:The bedside monitor risk management system based on the risk assessment management model can realize the efficient management of bedside monitors for critically ill neurosurgical patients,and improve the operating efficiency and quality of the equipment on the basis of ensuring the life safety of patients.

Objective To observe the effects of Renshen Yimai Prescription on oxidative stress and vascular aging in ApoE-/-mice;To explore its mechanism of intervention in vascular aging.Methods Forty ApoE-/-mice were divided into model group,Western medicine group(rosuvastatin,2.6 mg/kg),TCM low-and high-dosage group(Renshen Yimai Prescription,4.29,8.58 g/kg),with 10 mice in each group.Another 10 C57BL/6J mice were set as normal group.A vascular aging model was established by ApoE-/-mice fed with a Western diet.Each medication group was given corresponding drugs by gavage for 12 consecutive weeks,the normal group and model group were given equivalent volume of pure water.HE staining and Masson staining were used to observe the morphological changes of aortic tissue,and ox-LDL content in serum was detected by ELISA,the contents of ROS,GSH,GPX and NAD+in serum were detected by colorimetric method,the expressions of SIRT1,p53,p21 and NOX4 protein in aortic tissue were detected by Western blot.Results Compared with the normal group,the model group mice showed significant fat deposition in the aorta,thickening of the intima and media,a significant decrease in elastic fibers,and an increase in collagen fibers;the serum contents of ox-LDL and ROS significantly increased(P<0.01),while the contents of GSH,GPX and NAD+significantly decreased(P<0.01);the expression of SIRT1 protein in the aortic tissue significantly decreased(P<0.05),the expressions of p21 and p53 protein significantly increased(P<0.01,P<0.05).Compared with the model group,a small amount of lipid deposition was observed in the intima of aorta in each medication group,with clearer membrane structures in each layer and reduced collagen fiber;the serum contents of ox-LDL and ROS in each medication group were significantly decreased(P<0.01),while the GSH content significantly increased(P<0.05,P<0.01),the NAD+content in TCM low-dosage group significantly increased(P<0.05);the expressions of p21 and NOX4 protein in aortic tissue of the TCM high-dosage group significantly increased(P<0.05,P<0.01).Compared with the Western medicine group,the TCM high-dosage group showed a significant decrease in ROS content(P<0.01)and a significant decrease in p53 protein expression(P<0.05).Compared with the TCM low-dosage group,the TCM high-dosage group showed a significant decrease in p21 protein expression(P<0.01)and a significant increase in NOX4 protein expression(P<0.01).Conclusion Renshen Yimai Prescription may reduce vascular endothelial damage by regulating oxidative stress levels and related protein expression,thereby playing a role in improving vascular aging.