Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

ObjectiveTo investigate the effects of Huayu Jiedu prescription on brain microvascular endothelial cells （BMECs） after oxygen-glucose deprivation （OGD） injury and to explore its intervention mechanisms. MethodsThe cell counting kit-8 （CCK-8） assay was used to determine the optimal OGD duration and the effective concentration of Huayu Jiedu prescription-containing serum. Cells were randomly divided into the blank serum medium group （KBXQ）， model group （OGD）， HYXQ group （OGD + Huayu Jiedu prescription-containing serum）， and 3-methyladenine （3-MA） group （OGD + 3-MA）. Cell morphology was observed under an inverted microscope. The numbers of autophagosomes and autolysosomes in cells were observed by transmission electron microscopy. Cell viability was determined using the CCK-8 assay. Cell apoptosis rate was detected using the TdT-mediated dUTP nick-end labeling （TUNEL） assay. The expression levels of microtubule-associated protein 1 light chain 3 （LC3） and Occludin were detected by immunofluorescence. The permeability of the cell monolayer was also measured. Cells were further randomly divided into the KBXQ group， model group （OGD）， HYXQ group， phosphatidylinositol-3 kinase （PI3K） inhibitor （LY294002） group （OGD + LY294002）， and HYXQ + LY294002 group （OGD + Huayu Jiedu prescription-containing serum + LY294002）. Western blot analysis was used to detect the expression levels of the autophagy-related key molecule yeast Atg6 homolog 1 （Beclin1）， LC3Ⅱ/LC3Ⅰ， selective autophagy adaptor protein （p62）， Occludin， phosphorylated （p）-PI3K， PI3K， phosphorylated protein kinase B （p-Akt）， Akt， phosphorylated mammalian target of rapamycin （p-mTOR）， and mTOR. ResultsOGD for 6 h was selected as the optimal modeling condition， and 5% was determined as the optimal volume fraction of Huayu Jiedu prescription-containing serum. Compared with the KBXQ group， the model group showed obvious cell damage under the inverted microscope， and transmission electron microscopy revealed markedly increased numbers of autophagosomes and autolysosomes. Cell viability was significantly decreased （P<0.01）， apoptosis rate was significantly increased （P<0.01）， LC3 fluorescence intensity was significantly increased （P<0.01）， Occludin fluorescence intensity was significantly decreased （P<0.01）， and monolayer permeability was significantly increased （P<0.01）. Compared with the model group， cell damage in the HYXQ group and the 3-MA group was significantly improved， the numbers of autophagosomes and autolysosomes were markedly reduced， cell viability was significantly increased （P<0.01）， apoptosis rate was significantly decreased （P<0.01）， LC3 fluorescence intensity was significantly decreased （P<0.01）， Occludin fluorescence intensity was significantly increased （P<0.01）， and monolayer permeability was reduced （P<0.05）. Western blot results showed that， compared with the KBXQ group， the model group exhibited significantly increased expression of Beclin1 and LC3Ⅱ/LC3Ⅰ （P<0.01）， while the expression levels of p62， Occludin， p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly decreased （P<0.01）. Compared with the model group， the HYXQ group showed significantly decreased expression of Beclin1 and LC3Ⅱ/LC3Ⅰ （P<0.01） and significantly increased expression of p62， Occludin， p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR （P<0.01）. In the LY294002 group， Beclin1 and LC3Ⅱ/LC3Ⅰ expression were significantly increased （P<0.05， P<0.01）， whereas the expression levels of p62， Occludin， p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly decreased （P<0.01）. Compared with the LY294002 group， the HYXQ + LY294002 group showed significantly decreased expression of Beclin1 and LC3Ⅱ/LC3Ⅰ （P<0.01） and significantly increased expression of p62， Occludin， p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR （P<0.01）. ConclusionHuayu Jiedu prescription has a protective effect on BMECs after OGD injury， which may be achieved by activating the PI3K/Akt/mTOR autophagy-related signaling pathway and inhibiting excessive autophagy， thereby protecting Occludin protein expression and endothelial barrier function.

Objective: To investigate the current status of benefit finding among young and middle-aged patients with type 2 diabetes mellitus (T2DM) and analyze its influencing factors, so as to provide a reference for improving the level of benefit finding in this population. Methods: From November 2022 to May 2023, young and middle-aged patients with T2DM aged 18-59 years hospitalized in the endocrinology departments of 2 tertiary hospitals in Hengyang City, Hunan Province were selected as survey subjects by a convenience sampling method. Basic demographic information was collected using a general questionnaire survey. Benefit finding, resourcefulness, and stigma were evaluated using the Benefit Finding Scale, the Chinese Version of the Resourcefulness Scale, and the Type 2 Diabetes Stigma Assessment Scale, respectively. A multiple linear regression model was used to analyze the influencing factors of benefit finding among young and middle-aged patients with T2DM. Results: A total of 305 young and middle-aged patients with T2DM were investigated, including 222 males (72.79%) and 83 females (27.21%). There were 231 cases aged 45-59 years, accounting for 75.74%. The scores for benefit finding, resourcefulness, and stigma were (42.86±6.06), (75.12±11.30), and (41.20±10.10), respectively. Multiple linear regression analysis showed that young and middle-aged patients with T2DM who were male (β′=0.088), aged 18-<45 years (β′=0.083), absence of diabetes complications (β′=0.124), and had higher resourcefulness scores (β′=0.679) had higher levels of benefit finding, while patients with higher stigma scores (β′=-0.097) had lower levels of benefit finding. Conclusion The level of benefit finding among young and middle-aged patients with T2DM was moderate, and was related to gender, age, diabetes complications, resourcefulness, and stigma.

The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

BACKGROUND:In the initial stage of growth plate injury inflammation,platelet-derived growth factor BB promotes the repair of growth plate injury by promoting mesenchymal progenitor cell infiltration,chondrogenesis,osteogenic response,and regulating bone remodeling. OBJECTIVE:To elucidate the action mechanism of platelet-derived growth factor BB after growth plate injury. METHODS:PubMed,VIP,WanFang,and CNKI databases were used as the literature sources.The search terms were"growth plate injury,bone bridge,platelet-derived growth factor BB,repair"in English and Chinese.Finally,66 articles were screened for this review. RESULTS AND CONCLUSION:Growth plate injury experienced early inflammation,vascular reconstruction,fibroossification,structural remodeling and other pathological processes,accompanied by the crosstalk of chondrocytes,vascular endothelial cells,stem cells,osteoblasts,osteoclasts and other cells.Platelet-derived growth factor BB,as an important factor in the early inflammatory response of injury,regulates the injury repair process by mediating a variety of cellular inflammatory responses.Targeting the inflammatory stimulation mediated by platelet-derived growth factor BB may delay the bone bridge formation process by improving the functional activities of osteoclasts,osteoblasts,and chondrocytes,so as to achieve the injury repair of growth plate.Platelet-derived growth factor BB plays an important role in angiogenesis and bone repair tissue formation at the injured site of growth plate and intrachondral bone lengthening function of uninjured growth plate.Inhibition of the coupling effect between angiogenesis initiated by platelet-derived growth factor BB and intrachondral bone formation may achieve the repair of growth plate injury.

BackgroundPatients with depressive disorder often exhibit impaired decision-making functions. However， the relationship between decision-making abilities and depressive and anxiety symptoms in these patients remains unclear. ObjectiveTo explore the characteristics of decision-making behavior in patients with depressive disorder， and to analyze its relationship with clinical symptoms. MethodsA total of 48 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were recruited from the Department of Psychosomatic Medicine of the Affiliated Hospital of Southwest Medical University from October 2020 to May 2023. Concurrently， 52 healthy individuals matched for age and gender were recruited from Luzhou as the control group. Beck Depression Inventory （BDI） and Beck Anxiety Inventory （BAI） were used for assessment， and decision-making behavior was evaluated using Probabilistic Reversal Learning （PRL） task. Indicators assessed included the number of trials to criterion， perseverative errors， win-stay rate and lose-shift rate. Spearman correlation analysis was used to assess the correlation between BDI and BAI scores and PRL task indicators. ResultsThe depression group showed a significantly higher lose-shift rate compared with the control group （t=3.684， P<0.01）. There were no statistically significant differences between two groups in trials to criterion， perseverative errors and win-stay rate （t=0.329， 0.132， 0.609， P>0.05）. In depression group， BDI and BAI scores were positively correlated with the win-stay rate（r=0.450， 0.398， P<0.01）. ConclusionPatients with depressive disorder are more likely to change their decision-making strategies following negative outcomes. Furthermore， the severity of depressive and anxiety symptoms is associated with a greater propensity to maintain existing decisions after receiving positive feedback. ［Funded by 2019 Joint Project of Luzhou Science and Technology Bureau-Southwest Medical University （number， 2019LZXNYDJ39］

Objective To study the damage effect of high-voltage electric shock on skin based on metabolomics,analyze its metabolic differences,and explore its injury mechanism.Methods A total of 16 SPF C57BL/6J male mice were divided into the electric shock group(head skin received electric shock treatment)and control group(head skin received electric shock acoustic-optical stimulation),and the skin appearance after treatment of mice in the two groups was observed.The histopathological changes caused by electric shock were analyzed by HE staining,EVG staining and Masson staining.GC-MS and LC-MS metabonomics were used to analyze the changes of skin metabolism spectrum and tissue metabolites after electric shock exposure,and the differential metabolites were analyzed.The obtained differential metabolites were combined and KEGG enrichment analysis was conducted.Results After high-voltage electric shock,the skin of mice could be damaged to the dermis,and the epidermis was partially thickened,lifted and separated.The structure of skin appendages in the dermis was destroyed,with a large number of inflammatory cells infiltrating and obvious swelling,accompanied by congestion,which led to severe skin inflammatory reaction and impaired skin barrier function.Metabonomics analysis suggested that the metabolites changed after electric shock exposure.KEGG enrichment analysis showed that electric shock significantly affected the central carbon metabolism pathway of cancer,pentose phosphate pathway,purine metabolism,glycine,serine and threonine metabolism processes,amino acid tRNA biosynthesis mechanism,glycerophospholipid metabolism pathway,pyrimidine metabolism pattern,glycolysis/gluconeogenesis,alanine metabolism process,glucagon signal pathway and so on.Conclusion High voltage electric shock can cause deep skin damage,disturb its energy metabolism and amino acid metabolism,and seriously interfere with its antioxidant and DNA repair system functions.

Objective:To evaluate the efficacy of liposomal bupivacaine transversus abdominis plane block (TAPB) in combination with general anesthesia for elderly patients undergoing laparoscopic radical resection of colorectal cancer.Methods:In this randomized controlled trial, 70 American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, aged 60-80 yr, with body mass index of 18-28 kg/m 2, scheduled for elective laparoscopic radical resection of colorectal cancer at the General Hospital of Ningxia Medical University from September 2023 to June 2024, were divided into 2 groups ( n=35 each) using a table of random numbers: liposomal bupivacaine group (LB group) and hydrochloride bupi-vacaine group (HB group). After anesthesia induction, bilateral TAPB was performed under ultrasound guidance. In LB group, 0.44% liposomal bupivacaine 30 ml was injected on each side. In HB group, 0.25% hydrochloride bupivacaine 30 ml was injected on each side. Total intravenous anesthesia was adopted for both groups. Patient-controlled intravenous analgesia (PCIA) with sufentanil was carried out after surgery. When the visual analogue scale (VAS) score at rest was ≥ 4 within 72 h after surgery, hydromorphone 0.5 mg was intravenously injected for rescue analgesia. The area under the curve of VAS scores at rest and during activity was calculated within 12-72 h after surgery. The first pressing time of patient-controlled analgesia (PCA) and the effective pressing numbers of PCA, requirement for rescue analgesia, and score for satisfaction with analgesia were recorded. The sleep quality on 1 day before surgery and 1, 2 and 3 days after surgery was evaluated using the Richards-Campbell Sleep Questionnaire. The occurrence of adverse reactions, duration of post-anesthesia care unit stay, time to first ambulation, time to first flatus, and time to first oral intake, and postoperative length of hospital stay were recorded within 72 h after surgery. Results:Compared with HB group, the area under the curve of VAS scores at rest and during activity was significantly reduced at 12-72 h after operation, the first pressing time of PCA was prolonged, and the effective pressing numbers of PCA was reduced, the rate of rescue analgesia was decreased, the score for satisfaction with analgesia was increased, the Richards-Campbell Sleep Questionnaire scores were increased on the 2nd and 3rd days after surgery, the duration of post-anesthesia care unit stay and postoperative length of hospital stay were shortened, and the incidence of postoperative nausea was decreased in LB group ( P<0.05). Conclusions:The efficacy of liposomal bupivacaine TAPB combined with general anesthesia is superior to that of hydrochloride bupivacaine TAPB combined with general anesthesia in elderly patients undergoing laparoscopic colorectal cancer radical resection.

Objective:To elucidate the mechanism of acute lung injury (ALI) by investigating the relationship of sirtuin 6 (SIRT6) with lactylation of mitochondrial fission 1 protein (FIS1) and mitophagy in mice.Methods:Twenty-four SPF-grade healthy wild-type C57BL/6 mice of either sex, aged 6-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=6 each) using a table of random numbers: sham operation group (group S), ALI group, ALI + agonist group (group AA), and ALI+ agonist+ lactate group (group AAL). The mouse ALI model was established by intratracheal instillation of lipopolysaccharide 5 mg/kg in anesthetized animals. Immediately after developing the model, UBCS039 30 mg/kg was injected via the tail vein in group AA, UBCS039 30 mg/kg was injected via the tail vein and L-lactic acid sodium 1 mg/g was intraperitoneally injected in group AAL, and vehicle 0.5 ml was given instead in group S. Another 6 Prkn-/- mice were selected and assigned to Prkn-/-+ ALI+ agonist group (group PAA), and UBCS039 30 mg/kg was injected via the tail vein immediately after developing the ALI model. The mice were anesthetized and sacrificed at 12 h after lipopolysaccharide instillation, and the lung tissue was obtained for determination of the FIS1 lactylation and ubiquitination levels, the binding levels of FIS1 to SIRT6 and Parkin (using co-immunoprecipitation), expression of PTEN-induced kinase 1 (PINK1), microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), and mitochondrial Parkin (by Western blot) and for microscopic examination of the pathological changes (after haematoxylin and eosin staining) which were scored. The wet/dry lung weight (W/D) ratio was calculated, and the apoptosis rate of cells in lung tissues was calculated by TUNEL assay. Results:Compared with group S, the FIS1 lactylation level, W/D ratio, apoptosis rate of cells, and lung injury score were significantly increased in group ALI ( P<0.05). Compared with group ALI, the FIS1 lactylation level, W/D ratio, apoptosis rate of cells, and lung injury score were significantly decreased, the binding level of FIS1 to Parkin and FIS1 ubiquitination level were increased, and the expression of PINK1, LC3Ⅱ and mitochondrial Parkin was up-regulated in group AA ( P<0.05). Compared with group AA, the FIS1 lactylation level was significantly increased, and the binding level of FIS1 to Parkin was decreased in group AAL, and the W/D ratio, apoptosis rate of cells, and lung injury score were significantly increased, the FIS1 ubiquitination level was decreased, and the expression of PINK1, LC3Ⅱ and mitochondrial Parkin was down-regulated in group AAL and group PAA ( P<0.05). Conclusions:SIRT6 inhibits FIS1 lactylation, increases the binding of FIS1 to Parkin, and thus promotes mitophagy, which is involved in the process of ALI in mice.