BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

Objective : To investigate the effect of long non-coding RNA LUCAT1 (lncRNA LUCAT1) on the biological behavior of MIA PaCa-2 in human pancreatic cancer cells , and to explore the potential role of LUCAT1 in the malignant progression of pancreatic cancer. Methods : The mutation and expression of LUCAT1 in pancreatic cancer were analyzed by GEPIA , the expression levels of LUCAT1 in human pancreatic ductal cells HPNE and hu- man pancreatic cancer cells were detected by q-PCR , and the expression and distribution of LUCAT1 in human pancreatic cancer tissues were detected by FISH . CCK-8 assay and Transwell assay were used to detect the effects of LUCAT1 on the proliferation , apoptosis , drug resistance , and migration of MIA PaCa-2 cells . Gene ensemble enrichment analysis was performed to compare the related signaling pathways involved in LUCAT1 , and Western blot assay was used to verify the protein expression level . Results : The results of GEPIA analysis showed that the expression level of LUCAT1 in human pancreatic cancer tissues was up-regulated , and the expression of LUCAT1 in human pancreatic cancer cells was significantly higher ( P < 0. 05 ) . Knockdown and overexpression of LUCAT1 could affect the proliferation , apoptosis , gemcitabine resistance , migration and invasion of pancreatic cancer cells , and the differences were statistically significant (P < 0. 05) . In addition , LUCAT1 affected p-Akt expression levels in pancreatic cancer and was inhibited after treatment with Akt inhibitor MK-2206 . Conclusion LUCAT1 regulates the malignant progression of MIA PaCa-2 in pancreatic cancer cells through the PI3K-Akt signaling pathway.

Objective:To explore the clinical effect of rejuvenation of lower eyelid through orbital septum fat and orbital repositioning combined with thermal compression.Methods:A total of 423 patients who underwent skin approach blepharoplasty with skin laxity accompanied by different degrees of lacrimal groove and palpebromalar groove deformity admitted to the Plastic Surgery Department of Hemangioma and Vascular Malformation, the Plastic Surgery Hospital of Chinese Academy of Medical Sciences, from April 2020 to January 2023 were selected, including 403 females and 20 males, aged 33-68 (45.0±11.1) years. During the operation, the combined subcutaneous and suborbicularis oculi approaches were used to separate the prezygomatic space and premaxillary space. In the space, the orbital septum fat flap was fixed with the orbital septum flap under the infraorbital margin by lmbricate suture, and the orbital septum was tightened with energy hemostasis device to reshape and strengthen the anatomical structure of the lower eyelid. The patients were followed up to evaluate the incision healing and complications after surgery.Results:All the 423 patients were followed up for 1-48 months. The patients were healed in one stage, without lower eyelid retraction, lower eyelid ectropion and other complications. The incision of the lower eyelid was concealed and smooth, and the depression of lacrimalgroove and palpebromalar groove and lower eyelid relaxation were improved significantly.Conclusions:For patients with lower eyelid bag skin laxity and different degrees of lacrimal groove and palpebromalar groove depression, the surgical design is reasonable, and the structure of orbital septum fat and orbital septum is reset, and the effect is reliable.

Objective To explore the application effect of upper abdominal moxibustion combined with bedside ultrasound monitoring of gastric residual volume(GRV)in pre-pyloric feeding in stroke patients.Methods Eighty stroke patients admitted to the Department of Rehabilitation Medicine of Zhejiang Provincial People's Hospital from January 1,to December 31,2023 were selected as the study subjects.They were divided into control group(n=38)and observation group(n=42)using a random number table method.All patients had a nasogastric tube for pre-pyloric feeding.The control group used the traditional syringe aspiration method to monitor GRV,while the observation group used upper abdominal moxibustion combined with bedside ultrasound to monitor GRV.The study compared the differences between two groups in terms of enteral nutrition intolerance,feeding complications,enteral nutrition compliance rate within 7 days of admission,time to achieve enteral nutrition compliance,and changes in hemoglobin(Hb),serum prealbumin,serum albumin(ALB),and serum transferrin before and after 14 days of feeding.Results The incidence rates of vomiting,abdominal distention,intra-abdominal hypertension,reflux,and aspiration pneumonia in observation group were lower than those in control group(P＜0.05).The rate of achieving intestinal nutrition standard within 7 days of hospitalization was significantly higher in observation group compared to the control group.The time to achieve intestinal nutrition standard was shorter in observation group compared to control group.Furthermore,after 14 days of feeding,the levels of Hb and ALB in observation group were higher than those in control group,and the differences were statistically significant(P＜0.05).Conclusion Upper abdominal moxibustion combined with bedside ultrasonic monitoring of GRV can significantly reduce intestinal nutrition intolerance and feeding complications during pre-pyloric feeding in stroke patients,shorten the time to achieve nutritional benchmarks,and improve nutritional status.

【Objective】 To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. 【Results】 The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P<0.05). The unqualified rate of HBsAg, anti HCV, anti HIV and anti TP was (0.15±0.09)%, (0.05±0.04)%, (0.06±0.03)% and (0.20±0.05)% respectively. The average unqualified rate, average hemolysis rate, average insufficient volume rate and the abnormal hematocrit rate of samples in 17 blood bank laboratories was 0.21‰, 0.08‰, 0.01‰ and 0.02‰ respectively. There were differences in the retest concordance rates of four HBsAg, anti HCV and anti HIV reagents, and three anti TP reagents among 17 blood bank laboratories (P<0.05). The usage rate of ELISA reagents was (114.56±3.30)%, the outage rate of ELISA was (10.23±7.05) ‰, and the out of range rate of ELISA was (0.90±1.17) ‰. There was no correlation between the out of range rate, outrage rate and usage rate (all P>0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P<0.05). A total of 443 HBV DNA positive samples were detected in all blood banks, with an unqualified rate of 3.78/10 000; 15 HCV RNA positive samples were detected, with an unqualified rate of 0.13/10 000; 5 HIV RNA positive samples were detected, with an unqualified rate of 0.04/10 000. The unqualified rate of NAT was (0.72±0.04)‰, the single NAT reaction rate [(0.39±0.02)‰] was positively correlated with the single HBV DNA reaction rate [ (0.36±0.02) ‰] (r=0.886, P<0.05). There was a difference in the discriminated reactive rate by individual NAT among three blood bank laboratories (C, F, H) (P<0.05). The median resolution rate of 17 blood station laboratories by minipool test was 36.36%, the median rate of invalid batch of NAT was 0.67%, and the median rate of invalid result of NAT was 0.07‰. The consistency rate of ELISA dual reagent detection results was (99.63±0.24)%, and the median length of equipment failure was 14 days. The error rate of blood type testing in blood collection department was 0.14‰. 【Conclusion】 The quality monitoring indicator system for blood testing process in Shandong can monitor potential risks before, during and after the experiment, and has good applicability, feasibility, and effectiveness, and can facilitate the continuous improvement of laboratory quality control level. The application of blood testing quality monitoring indicators will promote the homogenization and standardization of blood quality management in Shandong, and lay the foundation for future comprehensive evaluations of blood banks.

Objective To investigate the expression of CD4+T cell subtypes and related inflammatory factors in patients with neutrophil-predominant frequent acute exacerbation chronic obstructive pulmonary disease(NE-FE-COPD).Methods COPD patients who were treated in the hospital from March 2019 to March 2021 were selected as the research objects.According to different phenotypes,they were divided into the infrequent exacerbator COPD group(IECOPD group,n=11),the eosinophilic dominant frequent acute plus severe COPD group(Eos-FE-COPD group,n=13),and the neutrophil dominant frequent exacerbator COPD group(NE-FE-COPD group,n=15).Patients with normal lung function and smoking history＞10 packs/year were the control group(CTRL group,n=9).Bronchoalveolar lavage fluid(BALF)was collected from each group,and the expression of CD4+T cell subtypes and inflammatory factors were detected by flow cytometry.The correlation between BALF and lung function and the frequency of acute exacerbation was ana-lyzed.CD4+CD28nullT cells and CD4+CD28+T cells were co-cultured with human airway epithelial cells(hAECs)and divided into co-culture group and Control group.The damage of hAECs was observed by immu-nofluorescence staining,and the mRNA and protein expression levels of ZO-1 and occludin were detected by RT-qPCR and Western blot.Results The proportion of CD4+CD28nullT cells and IL-1β level in BALF in the NE-FE-COPD group were higher than those in the CTRL group,the IE-COPD group,and the Eos-FE-COPD group,and the difference was statistically significant(P＜0.05).The proportion of CD4+CD28nullT cells and IL-1βlevel were negatively correlated with lung function(P＜0.05),and positively correlated with acute ex-acerbation frequency(P＜0.05).Compared with the Control group,hAECs tight junctions were damaged in the co-culture group,and mRNA and protein expression levels of ZO-1 and occludin decreased,with statistical significance(P＜0.05).Conclusion CD4+CD28nullT cells and IL-1β may be involved in the occurrence and de-velopment of NE-FE-COPD.

Objective: To systematically evaluate the correlation between selenium in the body and the risk of chronic kidney disease (CKD), so as to provide insights into CKD prevention and control. Methods: Publications pertaining to the correlation between selenium level and CKD were retrieved from electronic databases, including CNKI, WanFang Data, PubMed and Web of Science from inception until July 28, 2022. Meta-analysis was performed using the software Stata 16.0, and all measures were expressed with standardized mean difference (SMD) and its 95%CI. The source of heterogeneity was analyzed using subgroup analysis and meta-regression, and sensitivity analysis was performed using the leave-one-out method. In addition, the publication bias was evaluated with d funnel plot, Egger's test and Begg's test, and the robustness of the result was evaluated using the trim and filling method. Results: A total of 2 990 publications were screened, and 63 eligible publications were included in the final analysis, including 18 cross-sectional studies, 40 case-control studies, 2 cohort studies and 3 randomized controlled trials (RCTs), which covered 5 099 CKD patients and 6 334 controls. Meta-analysis showed lower selenium levels in CKD patients than in controls (SMD=-1.828, 95%CI: -2.132 to -1.523, P<0.001). Subgroup analysis showed lower selenium levels among CKD patients than among controls from Asia, Europe and multiple continents (P<0.05), and lower selenium levels were detected in patients undergoing conservative treatment, hemodialysis and peritoneal dialysis than in controls (P<0.05), while the selenium levels were significantly lower in CKD patients than in controls in cross-sectional studies, case-control studies and RCTs (P<0.05). The selenium level was significantly lower among CKD patients than among controls regardless of the study year, sample size and score for quality of publications (P<0.05). Sensitivity analysis showed robustness of this meta-analysis. Publication bias was identified by funnel plot, Begg's test and Egger's test, and the robustness of the result was found using the trim-and-fill method. Conclusion There may be a possible correlation between selenium and the risk of CKD.

Objective:To explore the oxidative stress of cerebral white matter lesion (WML) and normal-appearing white matter (NAWM) with in vivo proton exchange rate (k ex) MRI on relapse-remitting multiple sclerosis (RRMS) patients. Methods:Clinical and imaging data of 37 patients (case group) with RRMS patients of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology were analyzed retrospectively from November 2018 to November 2021, including 11 males and 26 females aged 18-41 (29±7) years. Another 22 age-matched healthy volunteers (control group) were recruited for the same period, including 4 males and 18 females aged 23-44 years with a median age of 25 (24, 28.25) years. All subjects received conventional MR protocols and chemical exchange saturation transfer imaging. The manifestation of WML on the k ex map and T 1WI images were assessed while the k ex values of WML, NAWM and normal white matter (NWM) of control group were quantitatively evaluated. Student′s t test was used to compare the k ex difference of WML and NAWM in the case group, NAWM in the case group and NWM in the control group, low-signal and isosignal WML in T 1WI. Spearman rank correlation was used to analyze the correlation of the k ex values of WML with patients′ expanded disability status scale (EDSS) score. Results:A total of 272 WML were found in the 37 RRMS patients, and 25.4% (69/272) were T 1-hypointense. The k ex value of WML in the case group [(932±108) s -1] was higher than that of NAWM [(771±26) s -1], and the difference was statistically significant ( t=8.95, P<0.001); the k ex value of NAWM in the case group [(771±26) s -1 ] was higher than that of NWM [(745±26) s -1] in the control group, and the difference was statistically significant ( t=3.96, P<0.001). The k ex value [(1 039±110) s -1] of WML with low signal at T 1WI was higher than that of WML with equal signal [(895±79) s -1], with a statistically significant difference ( t=9.78, P<0.001). Correlation analysis showed that the k ex value of WML in the case group was positively correlated with the EDSS score ( r=0.54, P<0.001). Conclusions:The elevated k ex values of WML and NAWM reflect the cerebral oxidative stress of RRMS patients and are positively correlated to the severity of tissue damage, which suggests the role of oxidative stress in RRMS lesion formation and brain atrophy.