Diabetic retinopathy (DR) is one of the most prevalent and vision-threatening microvascular complications of diabetes mellitus, yet its pathogenesis extends far beyond vascular injury alone. As the retina is among the most energy-demanding tissues in the body, its neurons, glial cells, pigment epithelial cells, pericytes, and endothelial cells are highly dependent on mitochondrial oxidative phosphorylation to maintain visual signal transduction, ionic homeostasis, and neurovascular integrity. This review summarizes current evidence indicating that mitochondrial dysfunction is not merely a downstream consequence of chronic hyperglycemia, but a central pathogenic hub that initiates, amplifies, and perpetuates retinal neurovascular degeneration in DR. Persistent hyperglycemia activates multiple abnormal metabolic pathways, including the polyol pathway, hexosamine pathway, protein kinase C signaling, advanced glycation end-product formation, and angiotensin II-related responses. Although these pathways differ mechanistically, they converge on excessive reactive oxygen species (ROS) generation, antioxidant depletion, and mitochondrial injury. Under diabetic stress, electron transport chain overload promotes mitochondrial ROS leakage, damages mitochondrial DNA, disrupts membrane potential, and impairs the transcription of key respiratory chain components. In parallel, mitochondrial quality-control systems become progressively compromised. The balance between fusion and fission shifts toward pathological fragmentation through reduced MFN1/2 and OPA1 activity and enhanced DRP1-mediated fission. Mitochondrial biogenesis is suppressed through inhibition of the AMPK/SIRT1/PGC-1α/NRF1/TFAM axis, while mitophagy changes from an early compensatory response to a later state of autophagic flux blockade and accumulation of dysfunctional mitochondria. Importantly, damaged mitochondria serve as signal amplifiers linking metabolic stress to inflammation and programmed cell death. Mitochondrial ROS, oxidized mitochondrial DNA, calcium overload, cardiolipin exposure, and membrane permeabilization activate interrelated death pathways, including intrinsic apoptosis, ferroptosis, and pyroptosis. Cytochrome C and apoptosis-inducing factor promote caspase-dependent and caspase-independent apoptosis; iron dyshomeostasis, glutathione depletion, GPX4 dysfunction, and lipid peroxidation drive ferroptosis; and mitochondrial danger signals activate the NLRP3 inflammasome and gasdermin-dependent pyroptosis. These pathways jointly damage the retinal neurovascular unit and contribute to pericyte loss, endothelial barrier breakdown, Müller cell dysfunction, retinal ganglion cell apoptosis, retinal pigment epithelial injury, and photoreceptor degeneration. This review also emphasizes the role of epigenetic regulation in stabilizing mitochondrial pathology. DNA methylation, histone modifications, and non-coding RNAs interact to silence mitochondrial protective genes, alter antioxidant responses, and maintain the “metabolic memory” of DR even after glycemic normalization. Therefore, mitochondrial dysfunction should be understood as a dynamic, multidimensional network rather than a single pathological event. Current clinical approaches, such as laser photocoagulation, intravitreal anti-VEGF therapy, and vitrectomy, mainly target advanced vascular lesions and are limited by invasiveness, incomplete responsiveness, recurrence, and potential adverse effects. Therapeutically, strategies targeting mitochondrial ROS, restoring mitochondrial dynamics, enhancing biogenesis, regulating mitophagy, inhibiting inflammasome activation, correcting epigenetic abnormalities, and improving targeted delivery systems show promising potential. However, major translational barriers remain, including retinal cell heterogeneity, stage-specific mitochondrial responses, insufficient organelle-specific drug delivery, and long-term safety concerns. A deeper understanding of mitochondrial regulatory networks may support earlier, more precise, and multi-target interventions for preventing or slowing DR progression.

Sichuan Province is a hilly schistosomiasis-endemic province in China with the highest endemicity and largest coverage. During the period of more than 70 years of integrated control, there are five distinct phases of schistosomiasis control in Sichuan Province, including baseline investigation, Oncomelania hupensis snail control, chemotherapy for both humans and livestock, management of source of Schistosoma japonicum infections, and sustained control and intensified surveillance and early warning, and a package of key interventions are implemented, including environmental modification, snail control with chemical treatment, large-scale chemotherapy for humans and livestock, management of source of S. japonicum infections, intensified integrated control, establishment of an early warning and surveillance system. As a result, schistosomiasis has been eliminated across all 63 disease-endemic counties (cities, districts) in Sichuan Province by June 2025. Government-led multi-sectoral collaborations, science and technology-supported precision control strategies, and a sustainable control model tailored to the ecological and socio-economic conditions in endemic regions are essential to achieving the target of schistosomiasis elimination in Sichuan Province.

This paper systematically analyzes schistosomiasis transmission risks during the elimination stage and reviews the evolution of the schistosomiasis surveillance system in China from a One Health perspective, with a special emphasis on schistosomiasis surveillance and response practices during the elimination stage from a One Health perspective. These practices include precise screening of human schistosomiasis under low-endemicity conditions, systematic monitoring of schistosomiasis in domestic and wild animals, ecological management of Oncomelania snails, and information-coordinated responses. Nevertheless, the current surveillance and response system for schistosomiasis suffers from challenges of insufficient cross-sectoral coordination and complex external environments, which constrain precise schistosomiasis surveillance and response in China. Therefore, it is urgently necessary to integrate coordination mechanisms, empower the surveillance system with technological innovation, improve capacity building, and actively promote diverse social participation in the One Health framework, so as to consolidate current schistosomiasis control achievements and achieve the target for schistosomiasis elimination across China, which may provide a replicable technical model for global zoonoses control.

Objective:To construct an evaluation indicator system for accessories of patient monitor,so as to provide a basis for clinical management,equipment procurement,and technical improvement for accessories of medical monitor.Methods:The initial selection indicators of corresponding accessories of three types of monitoring of medical monitors,including electrocardiogram(ECG),blood oxygen saturation(SpO2)and non-invasive blood pressure(NIBP),were determined through literature research,expert consultation,and actual investigation.The Delphi method was adopted to conduct two rounds of questionnaire consultation for experts from clinical medicine,biomedical engineering and other fields in medical institutions included Sichuan Provincial People's Hospital,The Affiliated Hospital of Southwest Medical University and Medical Institute of Chengdu Institute of Metrology Verification and Testing.The evaluation indicators were screened and optimized,and the Analytic Hierarchy Process(AHP)was used to calculate the weights of each indicator.The consistency test was conducted to verify the rationality of the evaluation indicator system.Results:The evaluation indicator system for accessories of medical monitor included three first-level indicators:clinical value,cost value,and management value.The number of second-level indicators about ECG,SpO2 and NIBP of evaluation indicator system were respectively 10,9 and 8,and the number of third-level indicators of that were respectively 20,19,and 14.In the first-level indicators,the clinical value had the highest weight,with 72.49%for ECG,70.88%for SpO2 and 70.32%for NIBP.In the second-level indicators,the accuracy(28.70%for ECG,38.13%for SpO2 and 43.03%for NIBP)and safety(27.47%for ECG,26.48%for SpO2 and 23.06%for NIBP)were the core indicators.The weights of cost value and management value were between 14.62%and 17.41%,and between 12.27%and 12.89%,respectively.Conclusion:The evaluation indicator system for accessories of medical monitor integrates multi-dimensional expert opinions and quantitative analysis,highlights the priority principle for clinical performance.It can provide theoretical support for optimizing selection about accessory for medical institutions,and improving quality of monitoring,and promoting standardized management in the industry.

Objective To explore the expression of Nudix hydrolase 5(NUDT5)protein in breast cancer tissues and its correlation with ultrasound signs and clinicopathological characteristics.Methods A total of 108 patients with breast cancer admitted to our hospital from October 2019 to April 2022 were selected as the research objects.Ultrasound examination was performed before operation to observe the ultrasound signs of patients.Immunohistochemical method was used to detect the expressions of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor 2(HER-2)in breast cancer tissues,and the expression levels of NUDT5 protein in breast cancer tissues and adjacent tissues,and the relationships of NUDT5 protein expression with ultrasound signs and clinicopathological characteristics of patients were analyzed.Results Among 108 patients,there were 62 cases with ER positive,60 cases with PR positive,and 28 cases with HER-2 positive.The positive expression rate of NUDT5 protein in breast cancer tissues was higher than that in adjacent tissues(P<0.05).The positive expression rate of NUDT5 protein was higher in breast cancer tissues with microcalcification,blood flow imaging grade(grade 2 to 3)and lymph node metastasis(P<0.05).The positive expression of NUDT5 protein was correlated with histological grade,ER and HER-2(P<0.05).The expression of NUDT5 protein in breast cancer tissue was positively correlated with ER negative and HER-2 positive(rs=0.463,0.398,P<0.05).Conclusion The positive expression rate of NUDT5 protein in breast cancer tissues is higher than that in adjacent tissues,and its expression has a certain correlation with microcalcification,blood flow imaging grade(grade 2 to 3),lymph node metastasis in ultrasound signs and histological grade,ER,and HER-2 in clinicopathological characteristics.

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

AIM:To investigate the potential mechanism of neutrophil extracellular traps(NETs)in the pla-centa during the pathogenesis of preeclampsia(PE).METHODS:Differential neutrophil infiltration in PE versus normo-tensive placentas was assessed using placental transcriptome sequencing data.Single-cell sequencing analysis of GSE173193 dataset was conducted to evaluate the expression of NETs formation-related genes in neutrophils from PE pla-centa and control placenta.Immunofluorescence and ELISA were used to measure NETs levels in placental tissues.Fol-lowing NETs generation and treatment of human extravillous trophoblast(EVT)HTR8/Svneo strain with NETs,RNA se-quencing was utilized to identify potential signaling pathways through which NETs regulate trophoblast function.RE-SULTS:Neutrophil infiltration,and expression of NETs formation critical genes,MPO(myeloperoxidase)and ELANE(elastase,neutrophil expressed),in neutrophils were significantly increased in PE placentas compared with controls.The level of NETs was elevated in PE placentas as well.The NETs significantly inhibited the migration of HTR8/Svneo cells.Disrupted F-actin arrangement,aggregate formation,and reduced paxillin expression were observed in NETs-treated HTR8/Svneo cells.Single-cell sequencing analysis revealed that focal adhesion and stress fiber pathways were down-regu-lated in the EVT of PE placenta.CONCLUSION:Neutrophil infiltration and NETs formation were increased in PE.The NETs may inhibit EVT migration by inducing stress fiber disassembly and down-regulating paxillin expression,thereby dis-rupting cytoskeletal organization and focal adhesion formation.