Aging involves the accumulation of various forms of molecular and cellular damage over time. Key features of aging, such as mitochondrial dysfunction, dysbiosis, and oxidative stress, are closely linked and largely driven by inflammation. This study examines the role of succinate, a key metabolite produced and utilized by cells of both host and microbes, and its receptor, succinate receptor 1 (SUCNR1), in age-related oral dysbiosis and inflammation. We examined young and aged wild-type (WT) and SUCNR1 knockout (KO) mice for this analysis. Our findings revealed significant aging-associated alveolar bone loss and succinate elevation in aged WT mice, along with notable changes in the oral microbiome. Conversely, aged KO mice showed reduced bone loss, lower succinate levels, less inflammation, and better-maintained microbial function. These results suggest that SUCNR1 is crucial in influencing aging-related succinate elevation, oral dysbiosis, and inflammation. Analysis of gene families and pathways in the oral microbiome demonstrated distinct aging-related changes between WT and KO mice, with the functional potential being preserved in the KO-aged group. This study underscores the importance of succinate elevation and signaling through SUCNR1 in regulating inflammation, alveolar bone loss, and shifts in the oral microbiome, offering potential targets for therapeutic interventions in age-related oral health issues.
Animals ; Dysbiosis/metabolism* ; Mice ; Succinic Acid/metabolism* ; Mice, Knockout ; Receptors, G-Protein-Coupled/metabolism* ; Inflammation/metabolism* ; Aging ; Alveolar Bone Loss/metabolism* ; Mouth/microbiology* ; Mice, Inbred C57BL ; Male ; Microbiota

ObjectivesTo analyze the spatial and temporal clustering characteristics and related influencing factors of late diagnosis of HIV/AIDS in Lanzhou， to identify its high-risk areas and time trends in Lanzhou， and to provide a theoretical basis for developing targeted HIV/AIDS prevention and control strategies in Lanzhou. MethodsThe subjects of this study were adult HIV/AIDS cases reported in Lanzhou City between 2011 and 2018. Data used in the study were sourced from the Lanzhou Center for Disease Control and Prevention and the Lanzhou Statistical Yearbook. To analyze the spatial distribution characteristics and influencing factors of the relative risk （RR） of late HIV/AIDS diagnosis， Bayes spatial-temporal model was used. ResultsA total of 1984 new HIV/AIDS cases were reported in Lanzhou from 2011 to 2018， with an mean age of 37.51 years and predominantly male （91.8%）. The number of late diagnosis cases was 982， with an mean age of 39.67 years and a predominance of males （91.8%）. Late diagnosis was more common in older individuals and women with HIV/AIDS. Chengguan District （51.1%）， Anning District （50.3%） and Yuzhong County （51.9%） had an above-average proportion of late diagnosis of HIV/AIDS. The proportion of late diagnosis cases in Lanzhou showed a fluctuating upward trend from 2011 to 2018. The results of Bayes spatial-temporal model showed that the risk of late HIV/AIDS diagnosis in Lanzhou had fluctuated from 2011 to 2015， and then increased rapidly after 2015 ［RR （95% credibility interval， 95%CI） increased from 1.01 （0.84， 1.23） to 1.11 （0.77， 1.97）］； the trends of risk of late diagnosis in Honggu district and three counties were similar to the overall trend in Lanzhou city， while the risk of late diagnosis in Chengguan District and Qilihe District showed a decreasing trend. The regions with the RR for late diagnosis greater than 1 included Yongdeng County （RR=1.07， 95% CI： 0.55， 1.96）， Xigu District （RR=1.04， 95% CI： 0.67， 1.49）， Chengguan District （RR=2.41， 95% CI： 0.85， 6.16）， and Qilihe District （RR=2.03， 95% CI： 1.10， 3.27）. Besides， the heatmap analysis showed that Chengguan District and Qilihe District were the hot spots. The influencing factors analysis showed that the higher GDP per capita （RR=0.65， 95% CI： 0.35， 0.90） and the larger proportion of males with HIV/AIDS cases （RR=0.53， 95% CI： 0.19， 0.92） could lead to the lower the relative risk of late HIV/AIDS diagnosis. However， the higher the population density （RR=1.35， 95% CI： 1.01， 1.81） caused the higher the risk of late diagnosis. ConclusionOur study shows the risk of late diagnosis of HIV/AIDS in Lanzhou was on the rise， and there are significant regional differences. GDP per capita， the proportion of males in HIV/AIDS cases and population density are influencing factors in the late diagnosis of HIV/AIDS. Therefore， for regions with a high risk of late diagnosis or related risk factors， targeted HIV screening and prevention services should be given priority in order to reduce the proportion and risk of late diagnosis of HIV/AIDS.

Inner ear diseases are common in the field of otolaryngology,including hearing loss,tinnitus and peripheral vestibular dysfunction.Their pathogenesis is relatively complex,which is one of the hot spots in current research.A large number of studies have demonstrated that sleep disorder is an important inducement of inner ear diseases.This paper reviews the impact of sleep deprivation on inner ear diseases in order to pro-vide a theoretical basis for the mechanisms of sleep deprivation on inner ear diseases.

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

This study aimed to explore the value of magnetic resonance imaging (MRI) T 2 mapping in the assessment of dermatomyositis (DM) and polymyositis (PM). Thirty-three confirmed cases (myosin group) and eight healthy volunteers (healthy control group) at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Kunming Medical University, from October 2016 to December 2017, were collected and analyzed. Multiple parameters of the myosin group were quantified, including creatine kinase (CK), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3, and complement C4. Disease status was evaluated using a panel of tools: myositis disease activity assessment tool-muscle (MDAAT-muscle), myositis disease activity assessment tool-whole (MDAAT-all), health assessment questionnaire (HAQ), medical outcomes study health survey short form-36 item (SF-36), hand muscle strength test (MMT-8) score, and MRI T 2 mapping of muscle (22 muscles in the pelvis and thighs) T 2 values. The results showed that in the myositis group, the measurements for CK, ESR, CRP, complement C3, and complement C4 were 457.2 (165.6, 1 229.2) IU/L, 20 (10, 42) mm/1h, 3.25 (2.38, 10.07) mg/L, 0.90 (0.83, 1.06) g/L, and 0.18 (0.14, 0.23) g/L, respectively. The scores for MMT-8, MDAAT-muscle, MDAAT-all, HAQ, and SF-36 were 57.12±16.23, 5.34 (4.00, 6.00), 34.63±12.62, 1.55 (0.66, 2.59), and 44.66±7.98, respectively. T 2 values were significantly higher in all 22 muscles of the pelvis and thighs of patients with DM or PM compared with the healthy controls [(54.99±11.60)ms vs. (36.62±1.66)ms, P<0.001], with the most severe lesions in the satrorius, iliopsoas, piriformis, gluteus minimus, and gluteus medius muscles. The total muscle T 2 value in the myositis group was positively correlated with CK, MDAAT-muscle, MDAAT-all, and HAQ ( r=0.461, 0.506, 0.347, and 0.510, respectively, all P<0.05). There was a negative correlation between complement C4, SF-36, and MMT-8 scores ( r=-0.424, -0.549, and -0.686, respectively, all P<0.05). Collectively, the findings from this study suggest that MRI T 2 mapping can objectively reflect the disease status of DM and PM.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective To analyze the relationship between bone mineral density (BMD) of infants over 6 months of age and exclusive breastfeeding and calcium nutrition guidance during pregnancy in Baoding area, and to provide evidence for clinical application. Methods A total of 308 infants over 6 months of age were selected from Baoding Maternal and Child Health Hospital from January 2020 to January 2023, and their BMD was measured by ultrasound. The level of 25 (OH) D3 in subjects' blood was detected. spearman correlation test was used to analyze the correlation between infant bone mineral density and exclusive breastfeeding and calcium nutritional guidance during pregnancy, and logistics regression model was used to analyze the independent factors affecting infant bone mineral density. Results The level of serum 25 (OH) D3 in normal BMD group was significantly higher than that in abnormal BMD group (P<0.05). The rate of exclusive breastfeeding and the guidance rate of calcium nutrition during pregnancy in normal BMD group were significantly higher than those in abnormal BMD group (P<0.05). There was a significant positive correlation between different bone mineral density and exclusive breastfeeding and calcium nutrition guidance during pregnancy (P<0.05). Serum 25 (OH) D3 level, exclusive breastfeeding rate and calcium nutritional guideline rate during pregnancy were independent protective factors for bone mineral density (P<0.05). Conclusion Bone mineral density (BMD) of infants over 6 months of age is positively correlated with exclusive breastfeeding and calcium nutrition guidance during pregnancy, and exclusive breastfeeding and calcium nutrition guidance during pregnancy are independent protective factors affecting BMD of infants over 6 months of age.

Objective　By exploring the function of sulfakinin (SK) and sulfakinin receptor (SKR) of Aedes aegypti, it laid a certain experimental basis and theoretical basis for the research and development of new insecticides targeting neuropeptides and their receptors. Methods　This study investigated the roles of SK and its receptor gene in Ae. aegypti using bioinformatics analysis and Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)/Cas9 knockout technology. Subsequently, RNA interference technology was employed to suppress the expression of SK or its receptor in adult mosquitoes. Lastly, transcriptome sequencing technology was utilized to identify and analyze differentially expressed genes between the interference group and the control group in order to gain insights into their functions. Results　It was found that there is only one SK receptor in Ae. aegypti. In addition, during the construction of mutant strains of Ae. aegypti SK and its receptor gene, it was found that only 2% of the G0 generation mutant strains mutated to form chimeras, with a large number of male chimeras dying, and only 14% of female chimeras being able to lay eggs, ultimately resulting in no effective G1 generation mutants. Transcriptome data showed, compared to the control group, 181 genes were significantly differentially expressed after interfering with the SK gene, with 62 genes significantly upregulated and 119 genes significantly downregulated. In addition, after interference with the sulfakinin receptor, 110 genes exhibited significant differential expression, including 20 upregulated and 90 downregulated genes. Cross-analysis of the two datasets identified 46 genes with significant expression changes after interference with sulfakinin or its receptor, with only 4 genes upregulated and the remaining 42 genes significantly downregulated, and the differentially expressed genes were mainly enriched in the metabolic pathway, endocrine system, and digestive system. Conclusions　The SK and its receptor gene are highly conserved and may primarily play roles in regulating the energy metabolism and digestion functions in Ae. aegypti, thus playing an important role in regulating insect growth and development.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.

Objective:To introduce the health insurance fund supervision model in Japan,compare the current situation of health insurance fund supervision in China,learn from experiences,and propose suggestions for improvement.Methods:By combining cases and regulatory effects,it introduces Japan's"guidance-inspection"based health insurance fund supervision model.Results:Japan's"guidance-inspection"based health insurance fund supervision model is relatively effective.Compared with China,it has a higher level of organizational hierarchy,focuses on education in its supervisory approach,clarifies the direction of patients'self-paid expences,and has a well-developed dual-way communication mechanism.Conclusion:China should establish a comprehensive health insurance fund supervision pathway,clearly define the resolution pathway for self-paid expenses caused by violations,and improve the mechanisms for negotiation and dispute resolution during the process.