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 explore the efficacy and mechanism of Euphorbia humifusa on acute kidney injury （AKI） based on network pharmacology， molecular docking and experimental verification. MethodsThe active components and targets of E. humifusa were retrieved from TCMSP and SwissTargetPrediction database， and the AKI targets were screened by GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. The drug targets and disease targets were intersected to construct a protein-protein interaction network， and the intersection targets were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. Discover Studio software was used to verify the molecular docking of key components and core targets. Gentamicin （GM） was used to induce AKI rat model. Control group， model group， verapamil （16 mg·kg^-1） group， E. humifusa extract （18， 54， 162 mg·kg^-1·d^-1） group and E. humifusa 70% ethanol extract （423 mg·kg^-1） group were continuously administered for 14 days. Urine volume was detected 24 h after modeling and administration. Serum creatinine （SCr）， Blood urea nitrogen （BUN）， 24-hour urine protein （24 hUTP） and uric acid （UA） content； the contents of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， carbon monoxide synthase （NOS） and lactate dehydrogenase （LDH） in kidney were measured. The levels of interleukin （IL）-6 and tumor necrosis factor （TNF）-α in serum were detected by enzyme linked immunosorbent assay（ELISA） kit. The pathological changes of renal tissue were detected by hematoxylin-eosin （HE） and Masson staining. Western blot was used to detect the expression of PI3K/protein kinase B（Akt）/NF-κB signaling pathway-related proteins. ResultsIn this study， 13 active components such as kaempferol， luteolin， apigenin， gallic acid and quercetin were screened and identified from E. humifusa. Through bioinformatics analysis， these components and AKI have a total of 289 targets， of which 62 are core targets， including Akt1， TNF， tumor protein p53（TP53） and IL-1β. These targets are mainly involved in the regulation of biological processes such as NF-κB signaling pathway， HIF-1 signaling pathway， TNF signaling pathway， PI3K/Akt signaling pathway and mitogen-activated protein kinase（MAPK） signaling pathway. In animal experiments， we successfully constructed a GM-induced AKI model in rats. Compared with the model group， E. humifusa extract could significantly reduce the levels of 24 hUTP， BUN and SCr in rats （P<0.01）， indicating its improvement effect on renal function. In addition， the extract of E. humifusa also significantly reduced LDH activity and MDA content in rat kidney tissue （P<0.05， P<0.01）， and significantly increased SOD， NOS activity and GSH content （P<0.05）， indicating that the extract of E. humifusa has the potential of anti-oxidation and protection of renal function. Further analysis of inflammatory factors showed that the levels of IL-6 and TNF-α in serum of rats treated with E. humifusa extract were significantly decreased （P<0.01）， indicating that E. humifusa extract had anti-inflammatory effects. In addition， the extract of E. humifusa can also regulate the protein expression of PI3K/Akt/NF-κB signaling pathway， which further confirmed its mechanism of reducing GM-induced AKI. ConclusionThe extract of E. humifusa has a significant therapeutic effect on acute kidney injury through its multi-component and multi-target mechanism. Its effect is reflected in improving renal function， anti-oxidation， anti-inflammation and regulating immune response. These findings provide a scientific basis for the application of E. humifusa in the treatment of acute kidney injury， and point out the direction for future drug development and clinical research.

Purpose: The role of the Clinical Treatment Score post-5 years (CTS5) in male breast cancer (MBC) remains unclear. This study aimed to investigate the characteristics and prognosis of CTS5 between MBC and female breast cancer (FBC). Materials and Methods: Patients diagnosed with human epidermal growth factor receptor 2–negative/estrogen receptor–positive breast cancer between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The chi-square test, Kaplan-Meier analysis, and multivariate Cox proportional hazard model were used for statistical analysis. Results: This study included 169,869 patients, comprising 168,422 (99.1%) FBC and 1,447 (0.9%) MBC patients. More MBC patients had intermediate risk (IR)/high risk (HR) disease compared to FBC patients (17.7% vs. 8.7%, p < 0.001). MBC patients had an inferior overall survival (OS) but similar breast cancer-specific survival compared to those with FBC. Sensitivity analyses showed that sex was an independent prognostic factor associated with OS but not breast cancer-specific survival (BCSS) in both the low-risk (LR) and IR/HR cohorts. Those with MBC exhibited significantly worse OS (p < 0.001) than FBC patients in both cohorts. In MBC patients, those with IR/HR disease had significantly worse OS (p < 0.001) and BCSS (p < 0.001) compared to those with LR disease. For FBC patients, the IR/HR group had also significantly worse OS (p < 0.001) and BCSS (p < 0.001) compared to the LR group. Conclusion Our findings highlight critical differences in clinical characteristics, treatment patterns, and outcomes between MBC and FBC, suggesting the need for sex-tailored approaches in breast cancer management.

To analyze the disease burden of hypertension in the elderly population from 1990 to 2021 and to predict future trends in China and globally, thereby providing insights for public health decision-making regarding older adults with hypertension in China.

Objective: To summarize the clinical characteristics, diagnosis, treatment and outcomes of rectal injury (RI) occurring after radical prostatectomy (RP). Methods: The clinical data of 513 patients with prostatic cancer undergoing RP in our hospital during Mar.2013 and Oct.2022 were retrospectively collected and statistical description of the occurrence of RI among them was conducted.There were a total of 7 patients with RI during operation and 1 progressed to rectourethral fistula (RUF).We summarized the clinical and pathological data of these 7 patients.The treatment strategies of RI/RUF after RP in 11 different centers were explored and summarized in combination with literature review. Results: Among the 7 RI patients, 6 developed RI during operation and healed after repair, while 1 progressed to RUF after operation.For this patient, conservative treatment failed and colostomy was performed along with bilateral ureteral stent placement and cystostomy.The RUF was repaired via the transanal approach.During the treatment process, recurrent and refractory bladder irritation symptoms and bladder spasms occurred.Data of 3203 patients who underwent RP in 11 different centers were collected; 56(1.75%) cases developed RI, 41 of which were detected and repaired during operation; 14(0.44%) developed RUF, 7 of which had fistula closed spontaneously and 7 received surgical repair. Conclusion: RI, especially RUF, is one of the rarest and severest complications after RP.Once RI is detected during operation, immediate and thorough two-layer suture repair should be performed.

BACKGROUND:Cell senescence is one of the major risk factors for osteoarthritis,but there is no widely accepted anti-osteoarthritis therapy targeting senescent cells.OBJECTIVE:To develop a feasible treatment strategy targeting senescent cells in osteoarthritis.METHODS:The cationic liposome containing rapamycin,RAPA@Lipo,was prepared by thin film dispersion method.Methylallylated hyaluronic acid hydrogel was synthesized,and RAPA@Lipo was added to the methylallylated hyaluronic acid hydrogel aqueous phase solution.The hydrogel microspheres were prepared by microfluidic equipment.Solid hydrogel microspheres(RAPA@Lipo@MS)were crosslinked under violet light.Primary human chondrocytes were co-cultured with RAPA@Lipo and RAPA@Lipo@MS,respectively.The biocompatibility of the materials was evaluated by CCK-8 assay and live/dead staining.Primary rat chondrocytes were cultured in four groups.Normal control group was cultured for 48 hours.The model group was stimulated with H2O2 for 24 hours to establish senescent cell model.RAPA@Lipo group and RAPA@Lipo@MS group were cultured for 24 hours after establishing senescent cell model with RAPA@Lipo and RAPA@Lipo@MS,respectively.After culture,immunofluorescence was used to observe the expression of p62 and type Ⅱ collagen.RT-PCR was used to detect the mRNA expression of interleukin 6,matrix metalloproteinase 13,type Ⅱ collagen,aggrecan,and ADAMTS-5.RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead staining showed that RAPA@Lipo and RAPA@Lipo@MS had good biocompatibility.(2)Compared with the normal control group,the protein expression of p62 was increased(P<0.05);the expression of type Ⅱ collagen was decreased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were increased(P<0.05);mRNA expression levels of type Ⅱ collagen and aggrecan were decreased(P<0.05)in the model group.Compared with the model group,the expression of p62 protein was decreased(P<0.05);the expression of type Ⅱ collagen was increased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were decreased(P<0.05);mRNA expression of type Ⅱ collagen and aggrecan increased(P<0.05)in the RAPA@Lipo@MS group.(3)These findings indicate that RAPA@Lipo@MS can control the quality of cells in vivo by enhancing autophagy,reduce senescent cells in vivo,and locally eliminate senescent cells and senescence-associated secretory phenotype factors in osteoarthritis,thereby slowing the progression of osteoarthritis and creating a cartilage microenvironment that promotes regeneration.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

Objective:To investigate the association between early reduction (within 3 days of admission) of serum triglyceride (TG) to 5.65 mmol/L and clinical outcomes in patients with acute pancreatitis extremely severe hypertriglyceridemia-induced (HTG-AP).Methods:The clinical data were derived from the PERFORM database, which prospectively collected clinical information on 613 HTG-AP patients admitted to 38 medical centers across China between November 2020 and June 2023 with serum TG level ≥11.3 mmol/L at admission. This study further screened extremely severe HTG patients with TG≥22.6 mmol/L. Patients were divided into the target-reaching group (TG≤5.65 mmol/L on day 3 after admission) and non-target-reaching group (TG>5.65 mmol/L on day3 after admission). The effect of early reduction of serum triglyceride to standard level on organ failure was observed. The primary outcome was organ failure-free days (OFFD) to 14 days of admission. Secondary outcomes included the presence of organ failure on day 7 and day 14, persistent organ failure (POF) to day 14, new-onset organ failure to day 14, maximum sequential organ failure assessment (SOFA) score to day 14, incidence of infected pancreatic necrosis (IPN) by day 60 of admission, length of ICU and hospital stay, mortality by day 60 of admission. The linear regression model was used for multivariate analysis. The subgroup forest plot was drawn to assess the effect of early reduction of TG on OFFD in different subgroups. The Kaplan-Meier method was used to plot the cumulative recurrence rate curve for the time to organ failure resolution and Log-Rank test was used for comparison between two groups.Results:Overall, 212 patients with HTG-AP were enrolled, with 118 in the target-reaching group and 94 in the non-target-reaching group. There was no significantly statistical difference on baseline TG level between two groups, but patients in non-target-reaching group had higher total cholesterol, LDL and CRP than those in target-reaching group. The median OFFD with 14 days of admission in target-reaching and non-target-reaching group was 14.0(11.0, 14.0) and 14.0(13.0, 14.0) days, respectively, without significant difference ( P=0.279). Moreover, there was no significant difference on the presence of organ failure on day 7 and day 14, POF to day 14, new-onset organ failure to day 14, maximum SOFA score to day 14, incidence of IPN by day 60 of admission, length of ICU and hospital stay, mortality by day 60 of admission between two groups. Results of multivariate analysis revealed that there was no significant difference on OFFD between two groups. Subgroup analyses were performed according to age, body mass index, baseline acute physiology and chronic health evaluation-Ⅱ (APACHE-Ⅱ) score, and whether there was organ failure at baseline. However, no association of early reduction of TG with OFFD to day 14 was shown in any subgroup. Among the 67 patients with organ failure at baseline, there was no significant difference in the time to organ failure resolution between target-reaching group and non-target-reaching group ( HR=1.256, 95% CI 0.746-2.116; P=0.343). Conclusions:For patients with acute pancreatitis complicated with extremely severe HTG (TG≥22.6 mmol/L), rapid TG decline (TG≤5.65 mmol/L on day 3 after admission) is not associated with reduced incidence and shorter duration of organ failure.

Objective:The high-quality clinical studies published in the field of hypertriglyceridemia associated acute pancreatitis (HTG-AP) were summarized to analyze the incidence and trends of HTG-AP in China.Methods:Clinical studies related to acute pancreatitis in PubMed, Medline, Cochrane Library and Web of Science from January 1, 2000 to November 12, 2021 were searched and screened. Keywords included China, acute pancreatitis, and clinical study. According to the inclusion and exclusion criteria, related literature were accurately selected and evaluated before extracting data. Meta-analysis was performed using R4.2 and RevMan5.3 software. The effect sizes of annual average percentage change (AAPC) for acute pancreatitis in different regions were merged and forest plot was drawn. Patients were divided into severe acute pancreatitis (SAP) group, moderately severe acute pancreatitis (MSAP) group and mild acute pancreatitis (MAP) group, and forest plot was drawn to analyze the AAPC of HTG-AP. Regression curve for time-dependent changes in the percentage of AP with different etiological factors was constructed.Results:Totally, 67 articles (33 randomized clinical trials, 34 retrospective cohort study) and 30 421 patients were included. The meta-analysis showed that the proportion of HTG-AP among AP patients was increasing over the past 20 years, with an AAPC of 0.52% (95% CI 0.34-1.39). In subgroup analyses, the proportion of HTG-AP in SAP and MSAP group both increased significantly, with the AAPC of 0.74% (95% CI 0.23-1.24) and 3.12% (95% CI 1.62-4.63), respectively. Furthermore, the proportion of HTG-AP among AP patients has shown an upward trend over the past 20 years with faster speed. The proportion of biliary pancreatitis among AP patients has also shown an upward trend, with the rate of increase gradually slowed. The proportion of alcohol-associated pancreatitis among AP patients has remained stable. Conclusions:Since 2000, the incidence proportion of HTG-AP has significantly increased in China with the rate of increase gradually quicker.

Objective:To investigate the impact of plasmapheresis therapy on the clinical efficacy in predicted severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) patients.Methods:The clinical data of 500 HTG-AP patients admitted to 36 medical centers across China in the Chinese Acute Pancreatitis Clinical Trials Group-PERFORM database from November 2020 to June 2023 were retrospectively analyzed. Besides the inclusion and exclusion criteria from PERFORM study, patients who had acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score ≥8 or CRP>150 mg/L on admission were included in the final analyses ( n=189). Patients were categorized into the plasmapheresis group ( n=51) and the routine treatment group ( n=138) according to the triglyceride-lowering therapies they received. General data, laboratory findings, AP severity, and clinical outcomes were recorded. Results:Patients undergoing plasmapheresis had higher initial triglyceride levels, APACHEⅡ score, SOFA score, and more organ failure than those receiving routine medical treatment. Results of multivariable logistic regression models showed that the plasmapheresis group, as compared to the routine treatment group, was neither associated with decreased risk of persistent organ failure within 14 days [54.9% (28/51) vs 37.7% (52/138), OR=0.89, 95% CI 0.36-2.21, P=0.810], nor with reduced incidence of organ failure on day 7 [17.7% (9/51) vs 15.9% (22/138), OR=0.60, 95% CI 0.19-1.88, P=0.378]. There was no significant difference on the dynamic changes of serum triglyceride within the first three days of admission ( P=0.108). Conclusions:Early plasmapheresis is not associated with reduced incidence of persistent organ failure in predicted severe HTG-AP patients.