Objective: To analyze the impact of premature death due to four major chronic diseases on life expectancy in Yangpu District, Shanghai Municipality from 2010 to 2021, so as to provide the evidence for formulating chronic disease prevention and control strategies. Methods : Mortality data of registered residents in Yangpu District from 2010 to 2021 were collected through the Death Information Registration and Management System of the Shanghai Municipal Disease Control and Prevention Information Management Platform. The premature death probability of malignant tumors, diabetes, cardiovascular and cerebrovascular diseases, and chronic respiratory diseases, and life expectancy of residents were calculated using the abridged life table method. Trends in premature death probability for four types of chronic diseases were analyzed using the average annual percent change (AAPC). The impact of premature death probability due to four chronic diseases on life expectancy was assessed by Arriaga's decomposition method. Results : The premature death probability due to four major chronic diseases in Yangpu District decreased from 9.88% in 2010 to 9.22% in 2021, showing an overall declining trend (AAPC=-0.540%, P<0.05). Among females, the premature death probability declined from 6.71% to 4.90% (AAPC=-2.715%, P<0.05), whereas no statistically significant trend was observed in males (P>0.05). Life expectancy increased from 82.52 years in 2010 to 84.50 years in 2021, with an overall upward trend (AAPC=0.244%, P<0.05). Life expectancy rose by 1.71 years for males and 2.34 years for females (AAPC=0.197% and 0.303%,both P<0.05). Declines in premature death probability from malignant tumors (AAPC=-0.967%, P< 0.05) and chronic respiratory diseases (AAPC=-3.071%, P<0.05) contributed to gains in life expectancy of 0.30 years and 0.03 years, with contribution rates of 12.18% and 1.29%, respectively. Changes in premature death probability due to diabetes as well as cardiovascular and cerebrovascular diseases were not statistically significant (both P>0.05), resulting in reductions in life expectancy of 0.05 years and 0.10 years, with contribution rates of -2.40% and -5.05%, respectively. Notably, an increase in premature death probability due to cardiovascular and cerebrovascular diseases among males (AAPC=1.673%) contributed to a decrease of 0.22 years in male life expectancy, whereas a decrease among females (AAPC=-3.824%) contributed to an increase of 0.03 years in female life expectancy, with contribution rates of -13.03% and 1.14%, respectively. Conclusions From 2010 to 2021, Yangpu District experienced an overall decline in premature death probability due to four major chronic diseases and an increase in life expectancy. Greater attention should be paid to the negative impacts of premature death probability from diabetes as well as cardiovascular and cerebrovascular diseases among males on life expectancy.

The Type III Secretion System (T3SS) serves as a pivotal virulence apparatus for numerous Gram-negative bacterial pathogens, enabling them to infect both animal and plant hosts. Functioning as a molecular syringe, the T3SS directly translocates bacterial effector proteins from the bacterial cytoplasm into the interior of eukaryotic host cells. These effectors are central weapons that precisely manipulate a wide spectrum of host cellular physiological processes, ranging from cytoskeletal dynamics to immune signaling, to establish a favorable niche for bacterial survival and proliferation. Among the diverse arsenal of T3SS effectors, the YopJ family constitutes a critical group of virulence factors. Members of this family are characterized by a conserved catalytic triad structure—a hallmark of the CE clan of cysteine proteases that has been evolutionarily repurposed to confer acetyltransferase activity. A defining and intriguing feature of these enzymes is their stringent dependence on a host-derived eukaryotic cofactor, inositol hexakisphosphate (IP₆), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF‑κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP₆-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.

Objective:To investigate the main causes of failed endoscopic retrograde cholangiopancreatography (ERCP) in children and the remedial treatment strategies.Methods:This retrospective cohort study analyzed the clinical data of 21 children who experienced failed ERCP at Beijing Children′s Hospital, Capital Medical University between January 2021 and December 2024. Data was collected included demographic information, clinical diagnoses, and ERCP outcomes. The annually trend in the ERCP failure rate was analyzed. Patients were categorized by etiology into the following groups: chronic pancreatitis, post-surgical status, pancreatic trauma, pancreas divisum, non-neoplastic pancreatic lesions, and ulcerative colitis. The relationship between etiologies and ERCP failure was analyzed by Fisher exact test.Results:A total of 175 ERCP procedures were included, of which 21 procedures failed (12.0%). The failure rate decreased annually from 2021 to 2024: 18.2% (4/22), 13.2% (5/38), 11.4% (5/44), and 9.9% (7/71), respectively. The etiological distribution among the 21 failed cases was as follows: chronic pancreatitis 28.6% (6/21), pancreatic duct stenosis following pancreatic trauma 23.8% (5/21), post-surgical status 14.3% (3/21), pancreas divisum 9.5% (2/21), acute pancreatitis 9.5% (2/21), non-neoplastic pancreatic lesions 9.5% (2/21), and pancreatic duct stenosis associated with ulcerative colitis 4.8% (1/21). Remedial treatments included surgical intervention (2 cases), ultrasound-guided percutaneous drainage (3 cases), and repeat ERCP (2 cases). For post-surgical and pancreatic trauma patients, failure was primarily due to bile duct stenosis, pancreatic duct stenosis, or pancreaticobiliary duct disruption. Active surgical interventions such as cholangiojejunostomy and pancreaticojejunostomy, and ultrasound-guided drainage following ERCP failure led to significant clinical improvement.Conclusions:A stratified management approach guided by etiology is essential following failed ERCP in children. Early and active remedial treatment, particularly surgical interventions, is recommended for post-surgical and pancreatic trauma cases.

Objective:To investigate the main causes of failed endoscopic retrograde cholangiopancreatography (ERCP) in children and the remedial treatment strategies.Methods:This retrospective cohort study analyzed the clinical data of 21 children who experienced failed ERCP at Beijing Children′s Hospital, Capital Medical University between January 2021 and December 2024. Data was collected included demographic information, clinical diagnoses, and ERCP outcomes. The annually trend in the ERCP failure rate was analyzed. Patients were categorized by etiology into the following groups: chronic pancreatitis, post-surgical status, pancreatic trauma, pancreas divisum, non-neoplastic pancreatic lesions, and ulcerative colitis. The relationship between etiologies and ERCP failure was analyzed by Fisher exact test.Results:A total of 175 ERCP procedures were included, of which 21 procedures failed (12.0%). The failure rate decreased annually from 2021 to 2024: 18.2% (4/22), 13.2% (5/38), 11.4% (5/44), and 9.9% (7/71), respectively. The etiological distribution among the 21 failed cases was as follows: chronic pancreatitis 28.6% (6/21), pancreatic duct stenosis following pancreatic trauma 23.8% (5/21), post-surgical status 14.3% (3/21), pancreas divisum 9.5% (2/21), acute pancreatitis 9.5% (2/21), non-neoplastic pancreatic lesions 9.5% (2/21), and pancreatic duct stenosis associated with ulcerative colitis 4.8% (1/21). Remedial treatments included surgical intervention (2 cases), ultrasound-guided percutaneous drainage (3 cases), and repeat ERCP (2 cases). For post-surgical and pancreatic trauma patients, failure was primarily due to bile duct stenosis, pancreatic duct stenosis, or pancreaticobiliary duct disruption. Active surgical interventions such as cholangiojejunostomy and pancreaticojejunostomy, and ultrasound-guided drainage following ERCP failure led to significant clinical improvement.Conclusions:A stratified management approach guided by etiology is essential following failed ERCP in children. Early and active remedial treatment, particularly surgical interventions, is recommended for post-surgical and pancreatic trauma cases.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Objective:To investigate the therapeutic effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) and stent implantation in the treatment of pancreaticobiliary injuries in children.Methods:A retrospective analysis was conducted on the clinical data of children diagnosed with pancreaticobiliary injury and undergoing ERCP and stent implantation at Beijing Children′s Hospital, Capital Medical University from January 2021 to December 2022. Demographic information, clinical data, endoscopic treatment methods, postoperative complications and clinical prognosis of the children were collected. The etiology, location of pancreaticobiliary injury, occurrence of complications after endoscopic treatment, and the time for improvement and recovery after endoscopic treatment were analyzed. The patients were divided into five groups according to the etiologies of pancreaticobiliary duct injuries: post-surgical, pancreatic trauma, acute pancreatitis, chronic pancreatitis, and systemic lupus erythematosus groups. They were also classified into four groups according to the sites of pancreaticobiliary duct injuries: common bile duct, pancreatic head, pancreatic body, and pancreatic tail groups. Multi-factor analysis of variance was used for comparing the time of improvement and recovery among different groups.Results:Among 22 patients, there were 8 males and 14 females, and the age was 7.5 (3.3,10.8) years. There were 19 cases of pancreatic or bile duct fistula, and 3 cases of pancreatic or bile duct stenosis. A total of 33 endoscopic procedures were performed on the 22 patients, out of which, 3 duct stenosis were failed to insert the stent because the catheter failed to pass through the stenosis site. The success rate was 91% (30/33). The pancreatic duct or bile duct stent was inserted, with the stent located at pancreatic or bile duct fistula. Postoperative complications included pancreatitis in 3 cases (9%, 3/33), hyperamylasemia in 5 cases (15%, 5/33), and postoperative infection in 4 cases (12%, 4/33). All patients were followed up for more than 1 year. Significant improvement was observed in external drainage and imaging monitoring among patients with successfully placed stents. There was no significant difference in the improvement time of ERCP in the treatment of pancreaticobile duct injury caused by different etiology ( F=0.65, P=0.637). However, there were significant differences in healing time ( F=6.46, P=0.004), among which the healing time of injuries caused by systemic lupus erythematosus was significantly different from that after surgery, trauma, acute pancreatitis and chronic pancreatitis (all P<0.05). There was no significant difference in the improvement and healing time among different injury sites (all P>0.05). Conclusions:ERCP and stent implantation can safely and effectively improve the clinical symptoms of children with pancreaticobiliary injury. Early intervention can improve long-term prognosis.

Objective To explore the mechanism by which curcumin improves behavioral deficits in mice with Parkinson's disease(PD)through fecal microbiota transplantation.Methods A subacute model of PD in mice was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Fecal microbiota from both the model group and the curcumin(Cur)-treated group(80 m g/kg)were collected and analyzed.The experiment involving fecal microbiota transplantation was structured into four distinct groups,fecal microbiota solvent transplantation group(FMTcon),model fecal microbiota transplantation group(FMTmodel),MPTP-induced model group(model),and model group subjected to fecal microbiota transplantation following curcumin treatment(model+FMTCur).The motor skills of the mice were assessed by using rod rotation,pole climbing experiment,and open field tests.Immunofluorescence techniques were employed to observe the expression tyrosine hydroxylase(TH)-positive neurons in the substantia nigra of the brain.Additionally,the gene expression of tumor necrosis factor-α(TNF-α)in the midbrain of mice was analyzed,alongside the protein expression of nuclear factor-κB(NF-κB)and nucleotide binding oligomerization domain-like receptor protein 3(NLRP3).Results The subacute PD animal model in mice was successfully established,and fecal microbiota were separated and gathered.The model group exhibited significant motor impairment,as evidenced by a shortened rod rotation time(P＜0.05),prolonged pole climbing time(P＜0.05),significantly reduced total movement distance within the open field(P＜0.001),and decreased time spent in the central zone(P＜0.01).The relative expression level of TH+neurons in the substantia nigra was significantly reduced(P＜0.01).Moreover,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with significant elevations in protein expression of NF-κB(P＜0.001),phosphorylated NF-κB(p-NF-κB)(P＜0.01),NLRP3(P＜0.001),and Caspase-1(P＜0.01).The transplanted model microbial group(FMTmodel)also exhibited motor impairment,manifested by a trend of shortened rod rotation time,prolonged pole climbing time,a significant decrease in total movement distance within the open field(P＜0.01),and a trend of shortened time spent in the central zone.The relative expression level of TH+neurons in the substantia nigra decreased significantly(P＜0.05).Additionally,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with notable elevations in the protein expression of NF-κB(P＜0.05),and Caspase-1(P＜0.01).Treatment with curcumin in the fecal microbiota transplantation group of mice(model+FMTCur)showed improvements in motor abilities,evidenced by shortened pole climbing time(P＜0.05),significantly prolonged rod rotation time(P＜0.01),and extended time spent in the central zone(P＜0.05).The relative expression level of TH+dopaminergic neurons in the substantia nigra increased significantly(P＜0.05).Moreover,mRNA expression of TNF-α in the midbrain decreased significantly(P＜0.01),along with notable reductions in the protein expression of NF-κB(P＜0.001),p-NF-κB(P＜0.01),NLRP3(P＜0.05),and Caspase-1(P＜0.01).Conclusion Fecal microbiota transplantation in PD model mice can induce behavioral deficits,damage TH+neurons in the substantia nigra,and trigger neuroinflammation in the brain.Subsequent curcumin treatment can ameliorate these deficits,reverse damage to TH+neurons,reduce neuroinflammatory factors,and decrease the expression of NF-κB and NLRP3 pathways.This preliminary evidence suggests that curcumin may improve Parkinsonian behavioral deficits in mice by modulating the gut microbiota.

ObjectiveTo understand the incidence and mortality trends of acute cardiovascular and cerebrovascular events in Yangpu District of Shanghai from 2009 to 2022, and provide a basis for the prevention and control of cardiovascular and cerebrovascular events. MethodsData were obtained from the Shanghai Acute Cardiovascular and Cerebrovascular Events Surveillance Platform. Data on the incidence and mortality of cardiovascular and cerebrovascular events in the population (age group, gender) from 2009 to 2022 were collected, and the Joinpoint Regression Program version 4.9 was used to calculate the average annual percent change (AAPC) in the incidence and mortality rates of acute cardiovascular and cerebrovascular events. ResultsFrom 2009 to 2022, the crude incidence and standardized incidence rate of acute cardiovascular and cerebrovascular events in Yangpu District showed no significant changes (AAPC=1.41%, P=0.569; AAPC=-1.03%, P=0.675), the crude mortality rate of acute cardiovascular and cerebrovascular events in Yangpu District did not change significantly (AAPC=-3.04%, P=0.213), while the standardized mortality rate showed a decreasing trend (AAPC=-6.23% P=0.014). From 2009 to 2022, the crude incidence rates and age-standardized incidence rates for both males and females in Yangpu District showed no significant changes. The crude mortality trends for both genders were not significant, while the age-standardized mortality rates showed a decline (AAPC=-5.33%, P=0.029; AAPC=-7.50%, P=0.006). The incidence rate and age-standardized incidence rate were higher in males than in females. The crude incidence rates in the 30‒, 40‒, and 45‒year-old age groups increased annually (AAPC=9.13%、7.11%、4.67%, all P=0.001), and the crude mortality ratse in the 60‒, 65‒, 70‒, 75‒, 80‒, and 85‒year-old age groups declined annually (AAPC=-4.24%, P=0.044; AAPC=-5.41%, P=0.028; AAPC=-6.73%, P=0.004; AAPC=-7.46%, P=0.002; AAPC=-8.24%, P=0.002; AAPC=-6.16%, P=0.035). ConclusionFrom 2009 to 2022, the crude incidence, standardized incidence rate and crude mortality rate of cardiovascular and cerebrovascular events in Yangpu District tended to be stable, and the standardized mortality rate showed a downward trend. Men, middle-aged and young people were the key groups in the prevention and treatment of cardiovascular and cerebrovascular diseases, and it should be continued to improve the ability of medical emergency and increase the integration of medical and prevention.

Osteoarthritis (OA) is a prevalent degenerative joint disease predominantly affecting the elderly and is characterized by cartilage degradation, synovitis, and subchondral bone sclerosis. Despite its widespread occurrence, no effective pharmacological interventions currently exist to halt or reverse disease progression. Polyphenolic compounds, a diverse class of plant-derived substances, have attracted considerable attention for their potent anti-inflammatory and antioxidant activities. This review summarizes recent advances in understanding the multifaceted roles of polyphenols in OA. Specifically, polyphenols protect chondrocytes and preserve the extracellular matrix by mitigating oxidative stress, suppressing inflammation, regulating autophagy and cholesterol metabolism, and inhibiting programmed cell death pathways, including apoptosis, pyroptosis, and ferroptosis. Furthermore, they exert protective effects on synovial tissue by regulating macrophage polarization and inhibiting pathogenic fibroblast activation, while also contributing to the maintenance of subchondral bone homeostasis. Recent progress in nanotechnology-based delivery systems, designed to overcome the poor solubility and limited bioavailability of polyphenols, is also highlighted. Collectively, this review integrates mechanistic insights with emerging therapeutic strategies, underscoring the potential of polyphenolic compounds as disease-modifying agents for OA.