The mitochondrial unfolded protein response(UPRmt)represents a crucial intracellular stress response mechanism that plays a fundamental role in maintaining mitochondrial and cellular homeostasis. Growing evidence suggests that dysregulation of UPRmt contributes significantly to the pathogenesis of various systemic disorders, including neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, as well as age-related pathologies. Emerging research has particularly highlighted the involvement of UPRmt in ocular diseases, including cataracts, glaucoma, and diabetic retinopathy. This comprehensive review examines the physiological functions of UPRmt and its regulatory mechanisms in age-related eye diseases. The roles of key UPRmt downstream effector molecules in ocular cell populations such as lens epithelial cells, retinal pigment epithelial cells, and retinal ganglion cells are systematically analyzed. Importantly, the dual regulatory nature of UPRmt in ocular pathophysiology is discussed, that is, its moderate activation promotes mitochondrial homeostasis, mitigates oxidative stress, and suppresses inflammatory responses, its chronic or excessive activation triggers apoptotic pathways, induces metabolic dysfunction, and ultimately accelerates disease progression. By elucidating these mechanisms, our review provides novel insights into ocular disease pathogenesis and proposes potential therapeutic strategies targeting UPRmt modulation for the prevention and treatment of age-related eye disorders.

BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

This article explores the application of Professor Zhou Zhongying's"focus on the core pathogenesis"concept in the con-text of epidemic hemorrhagic fever and examines how Academician Tong Xiaolin has inherited and developed Professor Zhou's experi-ences.Influenced by Professor Zhou Zhongying's academic thoughts and considering the contemporary context,Academician Tong Xia-olin,drawing on years of clinical experience,has proposed a new set of Nineteen Pathogenic Factors.Building upon the foundation of the Nineteen Pathogenic Factors in the The Yellow Emperor's Inner Classic,this new framework enriches and expands the understanding of disease location,etiology and pathogenesis,disease classification,and pays attention to a comprehensive understanding of diseases.It emphasizes that the process of seeking the underlying mechanisms should be approached from three aspects:dynamic,state,and condition,rather than solely focusing on the immediate clinical manifestations.This comprehensive approach to understand-ing disease development offers a fresh perspective and contributes to the application of traditional Chinese Medicine in the diagnosis and treatment of modern diseases.

The Menghe Medical School is a highly influential academic school of Chinese medicine in China.Its academic features are mainly learning from others'strengths,openness and tolerance;integrity as the foundation,communication as the strength;harmo-ny as the way,and agility as the technique.The Menghe Medical School originated in Menghe,developed in Shanghai,spread all over the country,and spread around the world.The reasons for the prosperity and development of the Menghe Medical School are analyzed.Among them,imperial doctors being rewarded and supported,the stars having their roots in Menghe,inheritance from teach-ers by blood,help from in-laws,and the establishment of education and leadership in development are the main factors.On the basis of inheriting the scholarship of Menghe Medical School,Professor Tong Xiaolin innovatively proposed academic ideas such as the train-ing path of Xiang thinking,state-target differentiation and treatment,and dosage and effectiveness of prescriptions and medicines,pushing the academic thought of Menghe Medical School to a new theoretical peak in the new era.Based on the majestic development path of the Menghe Medical School,the implications for the inheritance,innovation and development of modern Chinese medicine are analyzed.

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.

Objective To evaluate the Mandarin tracking of noise tolerance(TNT)test material and compare the differences between the average tolerable noise level(aTNL)value obtained from assessment and the program-estimated tolerable noise level(eTNL).Methods A total of 25 subjects with normal hearing and aural communica-tional ability were selected to undergo two of the mandarin TNT tests successively(respectively test 1,C1;test 2,C2),and 13 of them completed the third test(C3)under the same test condition as test 2 at least 1 week later.The stimulus for the three test conditions was presented with"speech 0°,continuous noise 180°".Results The aTNL of 25 participants for C1 and C2 was 83.42±3.09 dB SPL and 83.50±3.18 dB SPL,respectively.The eTNL of 25 participants for C1 and C2 were 84.08±3.53 dB SPL and 83.95±3.85 dB SPL,respectively.The aTNL and eT-NL for 13 subjects who participated in C3 was 83.16±2.13 dB SPL and 83.18±2.64 dB SPL,respectively.The intra-session(C1 vs C2)and inter-session(C2 vs C3)test-retest reliability were 2.36 dB and 2.75 dB,respectively.Pearson correlation analysis showed that intra-session(r=0.837,P＜0.001)and inter-session(r=0.867,P＜0.001)test-retest reliability was good.There was no statistical difference between aTNL and eTNL in the other TNT tests(P＞0.05 for both)except that aTNL and eTNL were statistically different in C1(P＜0.01),and more than 90％of the subjects could obtain eTNL within 1 minute.Conclusion The test-retest reliability of Mandarin tracking of noise tolerance test is good,with advantages of high reliability and efficiency.

Strengthening Party building within public hospitals is crucial for their healthy development in accordance with the Party's objectives.The party branch,as the grassroots organizational unit,is essential for bridging the gap between its con-struction level and the demands of practical tasks,a matter of significant interest to hospital administrators.This study delves into the current perceptions of high-quality construction among grassroots party branches in certain public hospitals in Jiangmen City,Guangdong Province.Suggestions and measures for high-quality construction of party branches are tailored,integrating the local context.The goal is to enhance the effectiveness of Party building,steering the hospitals towards high-quality development and fortifying the Party's grassroots governance foundation.

Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.

Objective To investigate the influence of Nei endonuclease Ⅷ-like protein 1(NEIL1)on H2O2-induced apoptosis and autophagy in lens epithelial cells(LECs).Methods Reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression of NEIL1 messenger ribonucleic acid(mRNA)in the anterior lens capsule and LEC line SRA01/04 cells from age-related cataract(ARC)patients and macular epiretinal membrane patients who underwent the clear lens extraction.SRA01/04 cells were then divided into the control group,OE-Vector group and OE-NEIL1 group.RT-PCR and Western blot(WB)were used to detect the overexpression efficiency.Subsequently,the cells were divided into the control group,H2O2 group,OE-Vector H2O2 group and OE-NEIL1 H2O2 group;cell viability was detected by Cell Count-ing Kit-8,WB was used to evaluate the expression of autophagy-related proteins(ATG7,P62,Beclinl,LC3-Ⅰ and LC3-Ⅱ)and apoptosis-related proteins(Bax and Bcl-2),and fluorescent staining was adopted to measure cell apoptosis and mito-chondrial membrane potential.Results The expression of NEIL1 mRNA in the anterior lens capsule samples from ARC patients was significantly lower than that of macular epiretinal membrane patients,and the expression of NEIL1 mRNA in the SRA01/04 cells in the H2O2 group was also lower than that in the control group(both P＜0.05).The results of RT-PCR and WB revealed that the expressions of NEIL1 mRNA and protein in the SRA01/04 cells of the OE-NEIL1 group were signif-icantly higher than those in the OE-Vector group(both P=0.000).Compared with the control group,the viability of SRA01/04 cells in the H2O2 group decreased,the expression of the Bax protein was up-regulated,the Bcl-2 protein was down-regulated,viable cells labeled with Mito-Tracker decreased,and apoptotic cells labeled with Annexin V-FITC in-creased,with statistical significances(all P＜0.05).Compared with the OE-Vector H2O2 group,in the OE-NEIL1 H2O2 group,the viability of SRA01/04 cells significantly improved,the autophagy-related proteins(ATG7,P62,Beclin1,LC3-Ⅰand LC3-Ⅱ)and Bcl-2 protein were significantly up-regulated,the Bax protein was down-regulated,viable cells marked with Mito-Tracker increased,and apoptotic cells labeled with Annexin V-FITC decreased(all P＜0.05).Conclusion Under the oxidative stress induced by H2O2,NEIL1 can promote autophagy of LECs,maintain homeostasis of LECs,and then increase cell viability and reduce apoptosis of LECs,participating in the occurrence and development of ARC.

OBJECTIVE: To observe the effect of puerarin on energy metabolism of the central nervous in acrylamide-exposed rats. METHODS: Specific pathogen free adult male SD rats were randomly divided into control group,model group,and puerarin low-,medium-,and high-dose groups,with 10 rats in each group. Intraperitoneal injection of acrylamide was given to rats in model group,and puerarin low-,medium-,and high-dose groups( 30 mg/kg body weight). Rats in control group were intraperitoneally injected with equal volume of 0. 9% sodium chloride solution. Rats in the puerarin low-,medium-,and high-dose groups were given puerarin of 40,80 and 160 mg/kg body weight,respectively after one hour of acrylamide exposure,three times a week for continuous 4 weeks. In the 4th week,the rats were sacrificed,the brain and spinal cord were isolated,and the ratio of adenosine diphosphate( ADP)/adenosine triphosphate( ATP),ATP activity and mitochondrial membrane potential( MMP) in brain and spinal cord tissue mitochondria were detected. RESULTS: The ADP/ATP ratio increased in mitochondria of brain and spinal cord tissue in model group and the three puerarin treatment groups( P < 0. 05),meanwhile the ATP synthase activity and MMP decreased compared with control group( P < 0. 05). The ADP/ATP ratio decreased in mitochondria of brain and spinal cord tissue( P < 0. 05),while MMP increased in mitochondria of brain tissue in the three puerarin treatment groups compared with model group( P < 0. 05). The ATP synthase activity increased in mitochondria of brain and spinal cord tissue of puerarin high-dose group( P < 0. 05),and MMP increased in mitochondria of spinal cord tissue of puerarin medium-does group and puerarin high-does group when compared with the model group( P < 0. 05). The ADP/ATP ratio in mitochondria of rat brain and spinal cord decreased with the increase of puerarin doses( P < 0. 05). The MMP of rat brain and spinal cord increased with the increase of puerarin dose( P < 0. 05). CONCLUSION: Puerarin enhances the energy metabolism function of the central nervous in rats by regulating mitochondrial ATP activity. It has certain protective effect on the mitochondrial membrane of central nervous system in rats exposed to acrylamide.