BACKGROUND:Type 2 diabetes mellitus impairs renal function,and studies have shown that exercise interventions can protect the kidneys.Irisin can protect renal function in diabetic nephropathy patients by restoring autophagy through inhibition of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway. OBJECTIVE:To explore whether exercise can restore autophagy and ameliorate renal injury by inhibiting over-activation of the renal PI3K/Akt/mTOR signaling pathway,as well as to analyze the differences in the effects of different modalities of exercise. METHODS:Six-week-old Sprague-Dawley rats were randomly divided into a blank control group(normal rats)and a diabetic group,and then the diabetic group was randomly divided into a diabetic model group,a moderate-intensity continuous exercise group,and a high-intensity intermittent exercise group after successful modeling using high-fat,high-sugar feeding plus intraperitoneal administration of low-dose 1%streptozotocin(30 mg/kg).The two exercise groups were subjected to 8 weeks of exercise intervention with different exercise intensities.The fasting blood glucose concentration was detected by glucose oxidase method,glycated hemoglobin levels was measured using a kit,serum insulin concentration was detected by Elisa method,and insulin resistance index was calculated.Gene expression of PI3K,AKT,mTOR,Beclin-1,podocin,and nephrin was detected by RT-PCR.Protein expression of mTOR and autophagy marker proteins LC3-1,LC3-2,and Beclin-1 was detected by western blot RESULTS AND CONCLUSION:Fasting blood glucose and glycosylated hemoglobin levels were highly significantly increased,insulin resistance levels were significantly increased,and insulin levels were significantly decreased in type 2 diabetic rats.Both exercises resulted in highly significant decreases in fasting blood glucose and glycosylated hemoglobin levels,significant decreases in insulin resistance levels and significant increases in insulin levels in type 2 diabetic rats.Insulin levels were significantly higher in the high-intensity intermittent exercise group compared with the moderate-intensity continuous exercise group.The expression of podocin and nephrind genes was significantly reduced in type 2 diabetic rats and two different forms of exercise significantly the gene expression.There was a further trend toward an increase in gene expression of podocyte-associated proteins in the moderate-intensity continuous exercise group compared with the high-intensity intermittent exercise group,but there was no significant difference.The mRNA and protein expression of PI3K,AKT and mTORC1 in kidney tissues of type 2 diabetic rats were significantly increased,and the expression of autophagy marker proteins Beclin-1 and LC3-2 and LC3-2/LC3-1 were significantly decreased.Both different forms of exercise significantly decreased the mRNA and protein expression of PI3K,AKT,and mTORC1,and significantly increased the autophagy marker proteins Beclin-1,LC3-2,and LC3-2/LC3-1 in renal tissues.Compared with the moderate-intensity continuous exercise group,there was a trend toward further decreases in mRNA expression of PI3K,AKT,and mTORC1 and protein expression of mTOR,and a trend toward further elevation of Beclin-1,LC3-2,and LC3-2/LC3-1 in the high-intensity intermittent exercise group,but only Beclin-1 showed a significant difference between groups.In summary,renal podocyte injury in type 2 diabetes mellitus with suppressed autophagy is closely related to aberrant activation of the PI3K/AKT/mTORC1 signaling pathway.Both moderate-intensity continuous exercise and high-intensity intermittent exercise can protect the diabetic kidney,reduce podocyte damage,and restore renal podocyte autophagy,which may be achieved by inhibiting the excessive activation of the PI3K/AKT/mTOR signaling pathway.High-intensity intermittent exercise shows a trend toward more favorable restoration of autophagy compared with moderate-intensity continuous exercise,but with a slight decrease in podocyte protein expression.

Objective:To explore the consistency of claudin 18.2 immunohistochemistry (IHC) using 4 different clone antibodies in gastric adenocarcinoma.Methods:A total of 226 gastric adenocarcinomas diagnosed and treated at the Drum Tower Hospital Affiliated to Nanjing University Medical College between January 2022 to March 2023 were included in this study. The cohort consisted of 165 males and 61 females, with a mean age of (61.3±12.1) years. Tumor tissues from radical resection specimens were collected for tissue microarrays. IHC detection of claudin 18.2 was performed using the EnVision method, utilizing 4 clones of antibody: OTIR157B5, 43-14A, EPR19202 and D313D22. The results were interpreted based on both the intensity of staining on tumor cell membranes and the percentage of positive tumor cells relative to the total tumor cells.Results:The positive cutoff value was set as moderately to strongly linear membrane staining in ≥75% of all viable invasive tumor cells, and clone OTIR157B5 demonstrated the highest positive expression rate at 52.2% (118/226). Additionally, the clones OTIR157B5, 43-14A, and EPR19202 were consistently and strongly positive, with all agreement rates of Cohen κ exceeding 0.8. In gastric adenocarcinoma and its three Lauren subtypes, OTIR157B5 exhibited clear membranous localization.Conclusions:Clone OTIR157B5 of claudin 18.2 antibody shows the highest rate of moderately to strongly linear membrane-positive staining, accounting for ≥75% of all viable invasive tumor cells, and clones 43-14A and EPR19202 show strong consistency and high sensitivity.

Objective:To combine the conventional audiometric curves and extended high frequency audiometric curves of patients with sensorineural deafness to form a full-frequency audiometric curve and to perform typing, so as to comprehensively understand the hearing status of patients with sensorineural deafness.Methods:This study was a cross-sectional study. The study subjects included 249 patients with sensorineural hearing loss who visited the Otolaryngology-Head and Neck Surgery outpatient clinic of the PLA General Hospital between July 2019 and December 2020. Among them, 146 were male and 103 were female, aged 11 to 80 years. The cases included 123 with mild hearing loss, 70 with moderate hearing loss, 32 with moderately severe hearing loss, 17 with severe hearing loss, 6 with profound hearing loss, and 1 with total deafness. According to the national standard GB/T16403-1996, conventional pure-tone audiometry (125-8 000 Hz) was performed on the 249 patients with sensorineural hearing loss to obtain their conventional-frequency hearing curves, which were then classified. Extended high-frequency pure-tone threshold testing (9 000-20 000 Hz) was conducted using extended high-frequency headphones, specifically including eight frequencies: 9 000, 10 000, 11 200, 12 500, 14 000, 16 000, 18 000, and 20 000 Hz. Ultimately, the full-frequency hearing curves (125-20 000 Hz) of each patient were obtained. The K-means clustering analysis method was used to classify the hearing curves based on their characteristics, and the results of the K-means clustering analysis were partially adjusted through manual screening.Results:The conventional hearing curves of all 249 patients were consistent with sensorineural hearing loss. The detection rates for extended high frequencies (9 000, 10 000, 11 200, 12 500, 14 000, 16 000, 18 000, and 20 000 Hz) were 96.79% (241/249), 94.38% (235/249), 87.95% (219/249), 78.31% (195/249), 65.46% (163/249), 22.09% (55/249), 10.84% (27/249), and 0.80% (2/249), respectively. The conventional-frequency hearing curves of the patients could be classified into the following types: low-frequency descending type (50/249, 20.08%), conventional-frequency steep descending type (78/249, 31.33%), conventional-frequency gradual descending type (58/249, 23.29%), conventional-frequency flat type (25/249, 10.04%), conventional-frequency 4 000 Hz notch type (30/249, 12.05%), and other types (8/249, 3.21%). By incorporating extended high-frequency hearing data, the full-frequency hearing curves of 235 patients were further classified into the following types based on different characteristics: full-frequency hill type (32/235, 13.62%), full-frequency ascending type (28/235, 11.91%), full-frequency 8 000 Hz notch type (14/235, 5.96%), full-frequency steep descending type (82/235, 34.89%), full-frequency gradual descending type (34/235, 14.47%), full-frequency shoulder-raising type (7/235, 2.98%), full-frequency shoulder-dropping type (25/235, 10.64%), full-frequency flat type (8/235, 3.40%), and other full-frequency types (5/235, 2.13%).Conclusions:Compared to the classification based on conventional-frequency hearing curves, the full-frequency hearing curves of patients with sensorineural hearing loss provide a more comprehensive representation of their overall hearing status. Patients with the same conventional-frequency hearing curve classification may exhibit different full-frequency hearing curve types, suggesting potential differences in the location and extent of pathological damage within their auditory systems.

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Background Precise prevention and control refers to the means of dividing a large area into several small areas, clarifying the disease information in each small area, and carrying out prevention and control program in the small areas accordingly. It is an important starting point for a comprehensive prevention and control program targeting liver cancer, which can make the prevention and control of liver cancer more accurate and efficient. At present, most of the mainstream research on liver cancer prevention and control at home and abroad is only on the provincial and municipal level, which is difficult to meet the requirements of precise prevention and control. Objective Taking S County, a typical county in Central China as an example, to explore the temporal and spatial distribution of liver cancer and environmental health risks at the township scale, so as to provide scientific reference for developing precise prevention and control program. Methods Based on the liver cancer data in the tumor registry data and related environmental variables of S County from 2009 to 2018, a spatiotemporal analysis was carried out by using geographic information system mapping, global Moran index analysis, and cold and hot spot detection. The correlations between liver cancer and various environmental factors [fine particulate matter (PM_2.5), aerosol optical depth (AOD), temperature, precipitation, proportion of cultivated land, normalized difference vegetation index (NDVI), population density, and per capita gross domestic product (GDP)] in S County were preliminarily evaluated by using geodetectors. The environmental factors and their cumulative exposure years that were closely related to the liver cancer in S County were investigated by random forest model. On this basis, the towns were categorized based on total, age-specified, and gender-specified incidences of liver cancer through quartile ranking, and precise prevention and control suggestions were proposed. Results ZD, HD and BYJ had the highest incidence rates of liver cancer, and the average annual incidence rate was 628/10⁵, 58.28/10⁵, and 40.21/ 10⁵, respectively. In addition to the above three townships, LW was a high incidence area of liver cancer in male population and people under the age of 60 years, whose average annual incidence rate was 50.47/10⁵ and 10.59/10⁵, respectively, while LianC was a high incidence area of liver cancer in female population and people aged 60 years and above, whose average annual incidence was 23.39/10⁵ and 131.10/10⁵ respectively. The incidence of liver cancer was closely related to population density, GDP per capita, NDVI, and AOD, and their importance indicators were 0.92, 0.50, 0.43, and 0.36, respectively. The average time interval between continuous exposure to dangerous environmental factors and the diagnosis of liver cancer was 10 years. Conclusion HD, ZD, and BYJ of S County should vigorously carry out liver cancer screening, diagnosis, and treatment in the follow-up prevention and control, while HD and LW should continue to implement environmental protection. LW needs to strengthen the prevention and treatment of liver cancer in male population and population under 60 years old. LianC needs to strengthen the prevention and control of liver cancer in female population and people of and over 60 years of age. The towns around HD need to prevent the sudden outbreak of liver cancer. In addition, it is also necessary to strengthen the willingness of people in the county, especially those of and over 60 years old, to participate in liver cancer screening. This study provides important reference for the analysis of environmental health effects at a fine scale and for the prevention and control of liver cancer and environmental protection in different populations.

[Objective] To investigate the differences in metabolomics between apheresis platelets stored at 4℃ and at 22℃ with agitation, aiming to provide a theoretical basis for the cold storage of apheresis platelets. [Methods] Samples were collected at four time points (d1, d5, d10, d15) for platelets stored at 4℃ (experimental group) and two time points (d1, d5) for platelets stored at 22℃ with agitation (control group). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was used to detect changes in platelet metabolome levels under different storage conditions. Platelet functional activity was assessed by thromboelastography (TEG) for maximum amplitude (MA) values and flow cytometry for CD62P activation rates. [Results] Metabolites in the glycolytic pathway, key metabolites in the tricarboxylic acid cycle (citrate, α-ketoglutarate), metabolites in the purine metabolism pathway (adenine, inosine monophosphate, guanine, etc.) and amino acid metabolites significantly decreased by d5 in the control group, whereas they remained stable in the experimental group. The content of fatty acid metabolites, such as prostaglandin G2, 13(S)-HOTrE, and linoleic acid, significantly increased in the control group. Statistically significant differences in MA values were observed between the two groups at d1 and d5 (P<0.05). However, in the experimental group, as the storage time extended, the MA values at d10 and d15 showed no significant difference compared to the control group at d5 (P>0.05). The CD62P activation rate between the two groups was statistically significant (P<0.05). Additionally, the CD62P activation rate of platelets in the 22℃ group increased rapidly from d1, while it rose gradually in the 4 ℃ group. [Conclusion] Platelets stored at 4 ℃ exhibit more stable metabolic activity and slower functional deterioration, which is beneficial for extending the effective storage period of platelets.

Theory and technology of Medical Immunology are widely used in scientific research.Our teaching and research group uses experimental teaching of Medical Immunology as a platform to carry out practice of scientific research project-based experi-mental system among"5+3"integration students.By completing a mini-project research including experimental design-experimental operation-research article writing,students cultivated scientific research thinking and exercised scientific research practice ability,and generally reported that the course is very difficult,but after completing it,it is very rewarding.

Objective:To explore the characteristics of nutrition self-management of home-based elderly chronic obstructive pulmonary disease (COPD) patients based on user persona, in order to provide reference for accurate home nutrition management.Methods:From July to December 2023, home-based elderly COPD patients in the Department of Respiratory and Critical Care Medicine of General Hospital of Ningxia Medical University were selected by convenience sampling method. The Mini Nutritional Assessment, COPD Assessment Test, Modified Medical Research Council Dyspnea Scale, Physical Activity Rating Scale-3, COPD Patients Self-Management Scale were used to conduct questionnaire survey. The SPSS 26.0 software was used to analyze the influencing factors of patients′ self-management of nutrition. Attributes with statistical significance ( P<0.05) were extracted as labels, and the visualization of patients′ self-management of nutrition portraits was completed in the form of pictures combined with labels. Results:A total of 320 questionnaires were distributed, and 309 valid questionnaires were collected. Among 309 home-based elderly COPD patients, there were 210 males and 99 females with an age of (69.14 ± 6.84) years old. According to the data analysis results, three dimensions of natural attributes, social attributes, and behavioral tracks were artificially extracted to construct three types of nutritional self-management user persona for home-based elderly COPD patients, respectively namely blind management type, independent attempt type, and powerless type.Conclusions:There are great differences in the nutritional status and self-management of home-based elderly patients with COPD. Accurate management measures can be developed based on user persona analysis to improve their nutritional status.

Objective:To explore the current status of quality of life of rheumatoid arthritis (RA) patients and its influencing factors based on the health ecology model (HEM) , and to provide a scientific basis for the development of health education programs for RA patients.Methods:From November 2023 to April 2024, 230 RA patients in the Department of Rheumatology and Immunology, General Hospital of Ningxia Medical University, were selected for the study using convenience sampling method. Patients were surveyed using the General Information Questionnaire, Quality of Life Instruments for Chronic Diseases in RA (QLICD-RA) , Health Literacy Management Scale, Social Support Rate Scale, Brief Illness Perception Questionnaire, 8-item Morisky Medication Adherence Scale, Pain Catastrophizing Scale, Chronic Disease Self-Management Study Measures, Fear of Progression Questionnaire-Short Form, Tampa Scale for Kinesiophobia and Visual Analogue Scale. Pearson and Spearman correlation was used to analyze the correlation between quality of life and health literacy, social support, disease perception, self-management behaviors, fear of disease progression, fear of exercise, medication adherence, pain catastrophizing, and pain in RA patients. Multiple linear regression was used to analyze the factors influencing the quality of life of RA patients.Results:A total of 230 questionnaires were distributed and 228 valid questionnaires were recovered, with a valid recovery rate of 99.13% (228/230) . The total QLICD-RA score of 228 RA patients was (137.53±27.57) . Duration of disease, disease perception, pain, pain catastrophizing, self-management behavior, joint deformity, morning stiffness duration, gastrointestinal response, sleep, social support, and main economic sources were the factors influencing the quality of life of RA patients ( P<0.05) , explaining 83.6% of the total variance. Conclusions:The quality of life of RA patients is moderate, and its influencing factors are distributed at all levels of HEM. Healthcare professionals can optimize the health education program for the main influencing factors of each layer, focusing on guiding patients to correctly understand the disease, stimulating the subjective initiative of patients, enhancing the ability of patients to actively manage the disease, and improving the quality of life of patients.