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Abstract Background The hyperpronation (HP) maneuver, known for its high success rate in reducing radial head subluxation after initial treatment failure, has gained significant favor among surgeons over the traditional supination-flexion (SF) maneuver. Despite its perceived advantages, the optimal treatment approach remains a topic of debate in the medical community due to uncertainties surrounding repeat and crossover reduction outcomes. Further research and clinical assessments are needed to establish a definitive treatment protocol ensuring optimal patient outcomes. This systematic review and meta-analysis aim to compare the efficacy of HP and SF maneuvers following unsuccessful initial treatments for radial head subluxation. Methods A thorough search of PubMed, Embase, and Cochrane Library databases up to May 13, 2024 was conducted. The Cochrane risk-of-bias tool evaluated study quality, and RevMan 5.3 facilitated systematic review calculations. Subgroup analyses explored reasons for heterogeneity by considering second reduction attempts with crossover and repeat maneuvers. Sensitivity analyses using fixed and random effects models were performed for ambiguous decisions. Results Nine studies with 170 patients were analyzed. The success rate for the second reduction was significantly higher with HP (OR = 2.48, 95% CI 1.18 to 5.20, P = 0.02) compared to SF. Repeat maneuver success rate for the second reduction also favored HP (OR = 3.79, 95% CI 1.57 to 9.16, P

This study investigates the structural response of in-service tunnels during excavation to provide an accurate evaluation of their service status. Existing theoretical analytical models typically simplify tunnels as continuous long beams, overlooking the reduction in stiffness at segment joints; this fails to reflect real-world conditions. To address this, a discontinuous beam-Pasternak model is established which accounts for joint stiffness weakening, and a theoretical solution for the tunnel’s structural response under excavation unloading is derived using the finite difference method. The model’s rationality and accuracy are validated through comparison against two sets of measurement data and calculation results from existing models. The results show that the displacement curve calculated by the proposed model shows discontinuity in the abrupt change at joints, which is advanced. In certain cases, the parameters of the proposed model can be aligned with those of existing models by using specific values. The influence of the critical parameters of the proposed model on the structural response of the in-service joined tunnel is further analyzed. The findings of this study may offer a practical method for swiftly assessing the structural response characteristics of in-service tunnels during excavation unloading.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is highly prevalent worldwide and poses a significant threat to men’s health, particularly affecting young men. However, the exact causes and mechanisms behind CP/CPPS remain unclear, leading to challenges in its treatment. In this research, a CP/CPPS rat model was established with complete Freund’s adjuvant (CFA), and berberine hydrochloride was administered through daily gavage to assess its therapeutic effects. The alterations in the gut microbiome induced by CP/CPPS and berberine hydrochloride were investigated through 16S ribosomal RNA sequencing of cecum content and colonic epithelial cells. To investigate the impact of the gut microbiome on CP/CPPS, a pseudo germ-free rat model was established, and fecal microbiome transplantation (FMT) was performed on these rats. In all, berberine hydrochloride demonstrated effective reduction of inflammation and oxidative stress in the prostate, offering significant therapeutic advantages for CP/CPPS. Through analysis of the gut microbiome using 16S ribosome RNA sequencing, distinct differences were observed between CP/CPPS rats and control rats, and Clostridium butyricum was identified as a key bacteria. Pseudo germ-free rats that underwent FMT from CP/CPPS rats or rats treated with berberine hydrochloride displayed varying levels of inflammatory cytokine production, oxidative stress, and activity of associated signaling pathways. In conclusion, the therapeutic potential of berberine hydrochloride in addressing CP/CPPS is highly significant. The gut microbiome has emerged as a critical factor in the development of CP/CPPS and plays a pivotal role in mediating the therapeutic effects of berberine hydrochloride.

Recently, lithium-ion capacitors (LICs) have developed rapidly and have been applied in many fields, such as power storage and new energy transportation. LICs utilize the cathode materials of electrical double-layer capacitors (EDLCs) and the anode materials of lithium-ion batteries (LIBs). This produces a unique energy storage mechanism different from those of LIBs and EDLCs, i.e., charge transfer and Li+ insertion and desorption. Consequently, LICs combine the advantages of LIBs and EDLCs with high energy density, high power density, and long cycle life. However, because of this unique energy storage protocol, LICs inherit the poor low-temperature performance of LIBs, severely limiting their widespread application. Sometimes, the electrolyte becomes more viscous or even solidifies, affecting normal ion transportation and charge transfer. An increase in impedance prevents the normal operation of LICs, severely limiting their all-weather applications. Improving the low-temperature performance of LICs has become an urgent issue and has received widespread attention from researchers. Electrodes and electrolytes are the main components of LICs, and numerous studies have shown that their relationship directly determines the energy storage process of LICs at low temperatures. Therefore, this article reviews the recent research progress on the design and fabrication of low-temperature LICs in terms of electrodes and electrolytes. First, the research on key electrode materials for high-performance low-temperature LICs is discussed, including chemical modification, surface modification, ion insertion, and the development of new electrode materials for rapid intercalation of traditional carbon-based materials. Second, the electrolyte system that matches the electrode material is critically reviewed. The fundamental reasons for the poor performance of LICs in low-temperature environments are comprehensively explained from the chemical properties, physical states, and reaction mechanisms, providing a sufficient theoretical basis for searching electrolyte systems with better low-temperature performance. Third, starting from the main components of the electrolyte–lithium salts, solvents, and additives, this article summarizes the past year’s progress on low-temperature electrolytes in LICs. Emphasis is placed on additives for LIC electrolytes, which, as the essence of the entire electrolyte system, are the most controllable factor throughout the electrolyte system and currently the most available factor for selection. They can reduce the viscosity of the electrolyte with minimal content and improve the low-temperature charging and discharging ability of LICs. Commonly used low-temperature additives such as fluoroethylene carbonate (FEC), vinylene carbonate (VC), ropylene sulfite (PS) and lithium difluorooxalate borate (LiODFB) demonstrate excellent low-temperature performance. Finally, the article summarizes the research progress of the new generation of low-temperature electrolytes and provides a tentative outlook toward next-generation LICs with a wide temperature range.

Abstract Background Trigger thumb is a prevalent hand condition observed in children, and its management remains a topic of considerable debate, ranging from mere observation to surgical intervention. In recent times, there has been a growing interest in exploring nonoperative treatments as alternatives to surgical procedures for managing pediatric trigger thumb. Gaining insight into the prevalence of spontaneous resolution in pediatric trigger thumb is of paramount importance. However, the literature presents a wide variation in estimates regarding the prevalence of this spontaneous resolution, highlighting the need for further investigation and consensus. The aim of this review was to estimate the overall prevalence of spontaneous resolution among pediatric trigger thumb. Methods This study meticulously followed the PRISMA guidelines and registered in the PROSPERO. The PubMed, Embase, and Cochrane Library databases were searched for all relevant studies up to May 2024.Inclusion criteria were studies reported only observation spontaneous resolution pediatric trigger thumb, aged up to 14 years, reported at least 10 thumbs and followed up time at least 3 months. Confounded intervention treatment measure studies were excluded. To synthesize the prevalence rates from individual studies, we employed a random-effects meta-analysis. In order to uncover the sources of heterogeneity and to compare prevalence estimates across different groups, we performed sensitivity and subgroup analyses. To meticulously evaluate the quality of the included studies, the Joanna Briggs Institute’s quality assessment checklist was employed. Furthermore, to assess the heterogeneity among the studies, both Cochran’s Q test and the I² statistic were utilized. Results A total of eleven studies were included for the final analysis, with 599 pediatric trigger thumbs. Our final meta-analysis showed that more than one-third of these pediatric trigger thumb cases resolved spontaneously, with a resolution rate of 43.5% (95% CI 29.6–58.6). Subgroup analyses showed that in terms of age at the first visit, the prevalence of spontaneous resolution in the less than 24 months group and in the 24 months or older group was 38.7%(95% CI 18.1–64.4)and 45.8%(95% CI 27.4–65.4), respectively. There was no significant difference between the two groups(P = 0.690). When analyzing follow up time, the prevalence of spontaneous resolution in the 24 months or longer group and in the less than 24 months group was 58.9%(95% CI 41.6–74.2)and 26.8%(95% CI 14.7–43.8), respectively.There was significant statistical differences between the two groups(P = 0.009). Based on the initial severity of interphalangeal (IP) joint flexion contracture, the prevalence of spontaneous resolution in the 30 degrees or less group and in the other measurements group was 54.1%(95% CI 31.5–75.1)and 37.1%(95% CI 21.9–55.4), respectively.There was no significant difference between the two groups(P = 0.259). Conclusion Our study demonstrates that a significant proportion of pediatric trigger thumbs resolve spontaneously. This finding highlights the benefits of early observation in managing this condition. By prioritizing non-operative observation, both parents and surgeons are better equipped to make informed decisions regarding the treatment of pediatric trigger thumb, potentially reducing the need for surgical intervention.

Abstract Background Chemoresistance remains a significant challenge in colorectal cancer (CRC) treatment, necessitating a deeper understanding of its underlying mechanisms. HOXC11 has emerged as a potential regulator in various cancers, but its role in CRC chemoresistance remains unclear. Methods Sulforhodamine B assay was employed to assess the cell viability of CRC cells following treatment with chemotherapeutic drugs. Immunofluorescence staining was performed to examine the subcellular localization of HOXC11 in normal and chemoresistant CRC cells. The Seahorse mito stress test was conducted to evaluate the mitochondrial respiratory function of CRC cells. Real-time PCR was utilized to measure the expression level and copy number of mitochondrial DNA (mtDNA). Results Our findings revealed that HOXC11 was overexpressed in CRC cells compared to normal colorectal cells and correlated with poorer prognosis in CRC patients. Knockout of HOXC11 reversed acquired chemoresistance in CRC cells. Furthermore, we observed a functional subset of HOXC11 localized to the mitochondria in chemoresistant CRC cells, which regulated mitochondrial function by modulating mtDNA transcription, thereby affecting chemoresistance. Conclusions In summary, our study reveals that HOXC11 regulates mitochondrial function through the modulation of mtDNA transcription, impacting chemoresistance in colorectal cancer cells. These findings underscore the significance of understanding the molecular mechanisms underlying chemoresistance and highlight the potential therapeutic implications of targeting mitochondrial function in CRC treatment.

ObjectivesChina’s national comprehensive medical reform (NCMR) is an important attempt in the reform of healthcare system, and quantitative evaluation of its effect is of great significance for continuously deepening medical reform, grasping the reform direction, and building a healthy China. Therefore, focusing on medical resources and medical burden, this study aims to systematically explore the policy effectiveness and the provincial heterogeneity of NCMR, as well as the potential influencing factors.MethodsUtilizing the collected multi-period panel data of 31 provinces in mainland China in 2006–2021, we regarded the release of the two batches of pilot provinces in NCMR as a quasi-natural experiment and comprehensively adopted a Staggered difference-in-differences (DID) model and Synthetic Control Method (SCM), combined with word frequency statistics and grouping regression analysis.ResultsNCMR can effectively increase the number of licensed physicians by 12.6% and reduce the per capita medical expense for in-patients by 7.2% in the pilot provinces. Furthermore, the NCMR policy effect in different pilot provinces shows various characteristics, and only Jiangsu, Zhejiang, and Chongqing achieve both the growth of medical resources and the reduction of medical expenditure. Meanwhile, word frequency statistics are conducted based on related policy descriptions and news reports on the official websites, so as to summarize the specific policy means in the three provinces, and provide a reference for other provinces to practice the healthcare reforms. Besides, extensibility analysis shows that the effect of NCMR is affected by the population aging and health status. Groups with low degree of population aging (low-AG)/high population health status (high-HE) performed a more obvious reform effect.ConclusionThis study provides beneficial policy implications for increasing medical resources, reducing medical burden, and promoting medical reform process.

The construction of smart cities plays a pivotal role in promoting regional sustainability by utilizing technology-driven urban development in the digital era. This study employs the difference-in-differences model to empirically analyze the impact of the smart city pilot policy on corporate carbon intensity, using data from Chinese A-share listed corporates from 2009 to 2021. The findings are as follows: First, the smart city pilot policy significantly reduces corporate carbon intensity in pilot cities, and this conclusion remains robust after a series of sensitivity tests. Second, the policy exhibits heterogeneous effects on corporate carbon intensity across different industries and city locations, with more pronounced effects observed in central cities, traditional industries, and heavily polluting industries. Third, mechanism analysis reveals that the policy reduces corporate carbon intensity through three channels: promoting technological innovation, increasing external market attention, and providing ex-ante government subsidies.

The transition from vernacular architectural patterns to current architecture in rural Iran has led to various socio-cultural and environmental problems in the last decade. This study explores the nature of this transition, which has been overlooked in the studies of vernacular architecture in Iran. Furthermore, this article contributes to the ongoing academic debate on the decline and transformation of vernacular architectural patterns in the context of modernization. It analyzes the forces behind the decline and rise of vernacular settlements in a case study area, the Salami region of the Khaf district in Iran’s Khorasan Razavi province, by exploring how it is possible to reinterpret vernacular architectural patterns in the context of current architecture to utilize the new developments in rural Iran not as an obstacle but as an opportunity for improvement. To this end, this article explores vernacular architectural patterns in a case study area in Iran, supported by socio-cultural aspects and the environmental conditions of the region. This study conducts architectural and anthropological fieldwork on three vernacular houses in a case study area and uses participant observation and informal interview methods to understand the people and their interaction with their built environment. The findings of this article thus contradict previous studies on learning from vernacular architecture by shedding light on vernacular architecture in Iran as a system by demonstrating the inextricable links between different vernacular architectural patterns. Therefore, this study argues that to draw lessons from vernacular architectural patterns for current architecture in rural Iran, it is necessary to limit its communication concerning people’s contemporary needs but not to neglect this communication completely.

Abstract Background Tuberculosis (TB) remains a pressing public health issue, posing a significant threat to individuals' well-being and lives. This study delves into the TB incidence in Chinese mainland during 2014–2021, aiming to gain deeper insights into their epidemiological characteristics and explore macro-level factors to enhance control and prevention. Methods TB incidence data in Chinese mainland from 2014 to 2021 were sourced from the National Notifiable Disease Reporting System (NNDRS). A two-stage distributed lag nonlinear model (DLNM) was constructed to evaluate the lag and non-linearity of daily average temperature (℃, Atemp), average relative humidity (%, ARH), average wind speed (m/s, AWS), sunshine duration (h, SD) and precipitation (mm, PRE) on the TB incidence. A spatial panel data model was used to assess the impact of demographic, medical and health resource, and economic factors on TB incidence. Results A total of 6,587,439 TB cases were reported in Chinese mainland during 2014–2021, with an average annual incidence rate of 59.17/100,000. The TB incidence decreased from 67.05/100,000 in 2014 to 46.40/100,000 in 2021, notably declining from 2018 to 2021 (APC = -8.87%, 95% CI: -11.97, -6.85%). TB incidence rates were higher among males, farmers, and individuals aged 65 years and older. Spatiotemporal analysis revealed a significant cluster in Xinjiang, Qinghai, and Xizang from March 2017 to June 2019 (RR = 3.94, P 71.73%), low sunshine duration (

Abstract. Background:. Alterations in macular thickness and vascular density before clinically visible diabetic retinopathy (DR) remain inconclusive. This study aimed to determine whether retinal manifestations in abnormal glucose metabolism (AGM) patients differ from those in the healthy individuals. Methods:. PubMed, Embase, and Web of Science were searched between 2000 and 2021. The eligibility criteria were AGM patients without DR. Primary and secondary outcomes measured by optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed and expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). A random-effects model was used in the data synthesis. The potential publication bias for the variables was evaluated using Egger’s test. Results:. A total of 86 observational studies involving 13,773 participants and 15,416 eyes were included. OCT revealed that compared to healthy controls, the total macular thickness of AGM patients was thinner, including the thickness of fovea (–0.24, 95% CI [–0.39, –0.08]; P = 0.002, I2 = 87.7%), all regions of parafovea (–0.32, 95% CI [–0.54, –0.11]; P = 0.003; I2 = 71.7%) and the four quadrants of perifovea; the thickness of peripapillary retinal nerve fiber layer (pRNFL), macular retinal nerve fiber layer (mRNFL), and ganglion cell layer (GCL) also decreased. OCTA indicated that the superficial and deep vascular density decreased, the foveal avascular zone (FAZ) area enlarged, and the acircularity index (AI) reduced in AGM individuals. Conclusions:. Retinal thinning and microvascular lesions have occurred before the advent of clinically detectable DR; OCT and OCTA may have the potential to detect these preclinical changes. Registration:. PROSPERO; http://www.crd.york.ac.uk/prospero/; No. CRD42021269885.

Introduction: Objective structured clinical examinations have traditionally been used to assess clinical skills. However, these face-to-face clinical assessments were hindered by physical and social restrictions imposed during COVID-19. This created a need to develop novel approaches for reliable assessment of clinical skills. We explored and evaluated a virtual exercise teleconsultation assessment (VETA) to replicate a teleconsultation setting where physiotherapy students were assessed on exercise prescription and coaching skills. Methods: We conducted a cross-sectional mixed-methods study using convenience sampling. A VETA was implemented for 172 physiotherapy students via Zoom to allow synchronous interaction with standardised patients (SPs). 67 students and 9 SPs completed two separate post evaluation surveys on themes relating to administration, support, authenticity, effectiveness, and value of the VETA. Likert-type responses were categorised as positive, neutral, or negative while coded qualitative responses were consolidated into themes by inductive content analysis. Results: 76% of students agreed that the assessment was authentic while 93% felt that the SPs were realistic and believable. Responders also highlighted important challenges including the limited camera viewing angle, time and space constraint, adequacy of equipment and reliability of connectivity. Exploratory factor analysis of responses revealed three latent constructs: (1) clarity of assessment, (2) clinical relevance, and (3) value of assessment. Conclusion: Despite the technical challenges, VETA demonstrated clarity and value as an alternative assessment and showed relevance to future telehealth practice, which is increasingly pervasive in clinical settings. This paper demonstrates a feasible approach for the virtual assessment of clinical competencies.

Summary: Background: Co-existence of efficient transportation networks and geographic imbalance of medical resources greatly facilitated inter-city migration of patients of infectious diseases in China. Methods: To characterize the migration patterns of major notifiable infectious diseases (NIDs) during 2016–2020 in China, we collected migratory cases, who had illness onset in one city but were diagnosed and reported in another, from the National Notifiable Infectious Disease Reporting System, and conducted a nationwide network analysis of migratory cases of major NIDs at the city (prefecture) level. Findings: In total, 2,674,892 migratory cases of NIDs were reported in China during 2016–2020. The top five diseases with the most migratory cases were hepatitis B, tuberculosis, hand, foot and mouth disease (HFMD), syphilis, and influenza, accounting for 79% of all migratory cases. The top five diseases with the highest proportions of migratory cases were all zoonotic or vector-borne (37.89%‒99.98%). The network analysis on 14 major diseases identified three distinct migration patterns, where provincial capitals acted as key node cities: short distance (e.g., pertussis), long distance (e.g., HIV/AIDS), and mixed (e.g., HFMD). Strong drivers for patient migration include population mobility and labor flow intensities between cities as well as the economic development level of the destination city. Interpretation: Collaborative prevention and control strategies should target cities experiencing frequent patient migration and cater to unique migration patterns of each disease. Addressing disparity in healthcare accessibility can also help alleviate case migration and thereby reduce cross-regional transmission. Funding: National Key Research and Development Program of China.

Introduction: Chemicals, such as MNU (N-methyl-N-nitrosourea) and NaIO3 (sodium iodate), are widely used to induce retinal degeneration in rodents. Streptozotocin (STZ) is an analog of N-acetyl glucosamine in which an MNU moiety is linked to a hexose and has a special toxic effect on insulin-producing pancreatic β-cells. It is commonly used to induce hyperglycemia to model diabetes. While intracerebroventricular injection of STZ can produce Alzheimer's disease independent of hyperglycemia, most retinal studies using STZ focus on the effects of hyperglycemia on the retina, but whether STZ has any impact on retinal cells independent of hyperglycemia is unknown. We aimed to investigate the role of cytotoxicity of STZ in rat retina.Methods: Intravitreal or subcutaneous injection of STZ was performed on newborn rats. Electroretinogram (ERG) and H&E staining investigated retinal function and morphological changes. Retinal cell types, cell death, proliferation, inflammation, and angiogenesis were studied by immunostaining. RNA sequencing was performed to examine the transcriptome changes of retinal cells after intravitreal injection of STZ.Results: Intravitreal (5 μg or 10 μg) or subcutaneous (30 mg/kg) injection of STZ at the early stage of newborn rats couldn’t induce hyperglycemia but caused NSIR (Neonatal STZ-induced retinopathy), including reduced ERG amplitudes, retinal rosettes and apoptosis, cell cycle arrest, microglial activation, and delayed retinal angiogenesis. STZ did not affect the early-born retinal cell types but significantly reduced the late-born ones. Short-term and long-term hyperglycemia had no significant effects on the NSIR phenotypes. RNA sequencing revealed that STZ induces oxidative stress and activates the p53 pathway of retinal cells. Locally or systemically, STZ injection after P8 couldn’t induce SINR when all retinal progenitors exit the cell cycle.Conclusion: NSIR in rats is independent of hyperglycemia but due to STZ’s direct cytotoxic effects on retinal progenitor cells. NSIR is a typical reaction to STZ-induced retinal oxidative stress and DNA damage. This significant finding suggests that NSIR may be a valuable model for studying retinal progenitor DNA damage-related diseases, potentially leading to new insights and treatments.

AimsThis study is designed to generalize and depict the research hotspots of endophthalmitis through bibliometric methods and software and analyze the evolutive tendency of the work on this severe disease over the past 30 years.MethodsThis study employed a rigorous bibliometric approach. We identified all endophthalmitis-related literature by conducting a comprehensive search of the Science Citation Index Expanded database under the Web of Science Core Collection. The data was then analyzed and visualized using CiteSpace and VOSviewer, two widely recognized software tools in the field of bibliometrics. CiteSpace was used to analyze the country distributions, dual map overlay of journals, keyword bursts, and co-cited references. VOSviewer was employed to describe the authors and co-cited authors, the journals, the co-cited journals, and the keywords co-occurrence network. This robust methodology ensures the reliability and validity of the study’s findings.ResultsA total of 2960 publications, including 2695 articles and 265 reviews, were included in this bibliometric study. There has been no shortage of endophthalmitis-related publications since 1993, with an apparent upward trend during recent years. Possible correlations with the COVID-19 pandemic are also analyzed. These studies were finished by 11,048 authors from 75 countries worldwide, with the United States in the lead. In the keyword co-occurrence network, except for the endophthalmitis term, cataract surgery becomes the keyword with the highest frequency. Different categories of endophthalmitis, including postoperative, post-injection, post-traumatic, and endogenous endophthalmitis, and antibacterial and anti-inflammatory therapies of infectious endophthalmitis, are discussed by categories. From the perspective of the timeline, postoperative and post-injection endophthalmitis were the dominant forms before and after the year 2000, respectively. Co-citation analyses reveal that the Endophthalmitis Vitrectomy Study (EVS) conducted in 1995 provides pivotal guidance for later research. Diverse pathogenic bacteria (e.g., Coagulase-negative Staphylococci, Propionibacterium acnes, Viridians Streptococci, and Bacillus cereus) or fungi (e.g., Candida, Aspergillus, and Fusarium) contribute to varying treatment principles and clinical prognosis, which should be taken seriously. In addition, intravitreal and intracameral antibiotics are the mainstay for treating and preventing infectious endophthalmitis, respectively.ConclusionOur bibliometric analysis provides an overview of dynamic evolution and structural relationships in the research field of endophthalmitis. The displayed hotspots and developmental directions have reference values for future investigation.

IntroductionInherited retinal diseases (IRDs) affect ∼4.5 million people worldwide. Elusive pathogenic variants in over 280 genes are associated with one or more clinical forms of IRDs. It is necessary to understand the complex interaction among retinal cell types and pathogenic genes by constructing a regulatory network. In this study, we attempt to establish a panoramic expression view of the cooperative work in retinal cells to understand the clinical manifestations and pathogenic bases underlying IRDs.MethodsSingle-cell RNA sequencing (scRNA-seq) data on the retinas from 35 retina samples of 3 species (human, mouse, and zebrafish) including 259,087 cells were adopted to perform a comparative analysis across species. Bioinformatic tools were used to conduct weighted gene co-expression network analysis (WGCNA), single-cell regulatory network analysis, cell–cell communication analysis, and trajectory inference analysis.ResultsThe cross-species comparison revealed shared or species-specific gene expression patterns at single-cell resolution, such as the stathmin family genes, which were highly expressed specifically in zebrafish Müller glias (MGs). Thirteen gene modules were identified, of which nine were associated with retinal cell types, and Gene Ontology (GO) enrichment of module genes was consistent with cell-specific highly expressed genes. Many IRD genes were identified as hub genes and cell-specific regulons. Most IRDs, especially the retinitis pigmentosa (RP) genes, were enriched in rod-specific regulons. Integrated expression and transcription regulatory network genes, such as congenital stationary night blindness (CSNB) genes GRK1, PDE6B, and TRPM1, showed cell-specific expression and transcription characteristics in either rods or bipolar cells (BCs). IRD genes showed evolutionary conservation (GNAT2, PDE6G, and SAG) and divergence (GNAT2, MT-ND4, and PDE6A) along the trajectory of photoreceptors (PRs) among species. In particular, the Leber congenital amaurosis (LCA) gene OTX2 showed high expression at the beginning of the trajectory of both PRs and BCs.ConclusionWe identified molecular pathways and cell types closely connected with IRDs, bridging the gap between gene expression, genetics, and pathogenesis. The IRD genes enriched in cell-specific modules and regulons suggest that these diseases share common etiological bases. Overall, mining of interspecies transcriptome data reveals conserved transcriptomic features of retinas across species and promising applications in both normal retina anatomy and retina pathology.

BackgroundRetroperitoneal lymphatic malformations (LMs) are rare. Currently, the treatment of retroperitoneal LMs remains challenging. This study aimed to examine the safety and efficacy of laparoscopic-assisted sclerotherapy for retroperitoneal LMs in pediatric patients.MethodsWe retrospectively reviewed patients treated with laparoscopic-assisted sclerotherapy for retroperitoneal LMs in a single tertiary medical center between July 2020 and February 2023. Doxycycline was prepared into a solution with a concentration of 10 mg/ml for use in sclerotherapy. Demographic data, clinical features, details of management, and outcomes were collected and analyzed.ResultsA total of six patients, comprising three males and three females, were identified. The LMs were categorized into four macrocystic and two mixed-cystic types. The mean age and weight were 52.2 months (range, 11–108 months) and 20 kg (range, 12.5–27.5 kg), respectively. Three patients presented with abdominal pain or distension, while the other three patients were asymptomatic. All six patients underwent a total of eight sclerotherapy sessions. Two patients experienced intra-cystic hemorrhage and required a second sclerotherapy session. Only one patient presented with vomiting after sclerotherapy, which resolved spontaneously. Five patients met the complete response criteria, and one patient met the effective criteria. The mean reduction in lesion size was 92.3% (range, 69.9%–99.6%). No further complications or recurrence were recorded during follow-up.ConclusionLaparoscopic-assisted sclerotherapy is a safe and effective approach for treating retroperitoneal LMs. This technique is applicable for both macrocystic and mixed-cystic retroperitoneal LMs.

Introduction: Intervertebral disc degeneration often occurs in the elderly population, but in recent years, there has been an increasing incidence of disc degeneration in younger individuals, primarily with mild degeneration.Methods: In order to explore the underlying mechanisms of disc degeneration in both young and aging individuals, we collected four types of nucleus pulposus (NP) single-cell sequencing samples for analysis based on Pfirrmann grading: normal-young (NY) (Grade I), normal-old (NO) (Grade I), mild degenerative-young (MY) (Grade II-III), and mild degenerative-old (MO) (Grade II-III).Results: We found that most NP cells in NO and MY samples exhibited oxidative stress, which may be important pathogenic factors in NO and MY groups. On the other hand, NP cells in MO group exhibited endoplasmic reticulum stress. In terms of inflammation, myeloid cells were mainly present in the degenerative group, with the MY group showing a stronger immune response compared to the MO group. Interestingly, dendritic cells in the myeloid lineage played a critical role in the process of mild degeneration.Discussion: Our study investigated the molecular mechanisms of intervertebral disc degeneration from an age perspective, providing insights for improving treatment strategies for patients with disc degeneration at different age groups.

Abstract The perplexing issues related to positive surgical margins and the considerable negative consequences associated with systemic chemotherapy have posed ongoing challenges for clinicians, especially when it comes to addressing bladder cancer treatment. The current investigation describes the production of nanocomposites loaded with gemcitabine (GEM) and cisplatin (CDDP) through the utilization of electrospinning technology. In vitro and in vivo studies have provided evidence of the strong effectiveness in suppressing tumor advancement while simultaneously reducing the accumulation of chemotherapy drugs within liver and kidney tissues. Mechanically, the GEM and CDDP-loaded electrospun nanocomposites could effectively eliminate myeloid-derived suppressor cells (MDSCs) in tumor tissues, and recruit CD8+ T cells and NKp46+ NK cells to kill tumor cells, which can also effectively inhibit tumor microvascular formation. Our investigation into the impact of localized administration of chemotherapy through GEM and CDDP-loaded electrospun nanocomposites on the tumor microenvironment will offer novel insights for tackling tumors. Graphical abstract Drug-loaded electrospun nanofibrous mats suppress bladder tumor growth by improving the tumor immune microenvironment.

Background: Excessive heat exposure can lead to hyperthermia in humans, which impairs physical performance and disrupts cognitive function. While heat is a known physiological stressor, it is unclear how severe heat stress affects brain physiology and function. Methods: Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures (Tre) attained 39.5°C, inducing exertional or passive hyperthermia, respectively. In a separate trial, blended ice was ingested before and during exercise as a cooling strategy. Data were compared to a control condition with seated rest (normothermic). Brain temperature (Tbr), cerebral perfusion, and task-based brain activity were assessed using magnetic resonance imaging techniques. Results: Tbr in motor cortex was found to be tightly regulated at rest (37.3°C ± 0.4°C (mean ± SD)) despite fluctuations in Tre. With the development of hyperthermia, Tbr increases and dovetails with the rising Tre. Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks, implying a reduced central motor drive in hyperthermic participants (Tre = 38.5°C ± 0.1°C). Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive hyperthermia. Executive function was poorer under a passive hyperthermic state, and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital cortex. Conversely, ingestion of blended ice before and during exercise alleviated the rise in both Tre and Tbr and mitigated heat-related neural perturbations. Conclusion: Severe heat exposure elevates Tbr, disrupts motor cortical activity and executive function, and this can lead to impairment of physical and cognitive performance.

The rising prevalence of pathogenic bacteria in livestock meat poses a growing public health concern in China. The determination of antimicrobial resistance (AMR) is critical for the clinical management of foodborne infections stemming from livestock meat consumption. This study aimed to assess the prevalence of pathogenic bacteria in livestock meat (pork, beef, and mutton) sampled in China in 2021 and to identify the most common AMR patterns among the isolated pathogens. A total of 2515 raw livestock meat samples were collected across 15 provinces in China during 2021. Pathogen detection, including Listeria monocytogenes, Salmonella, and diarrheagenic Escherichia coli (DEC), followed China’s national food safety standards. All Salmonella isolates underwent serotyping via slide agglutination. Antimicrobial susceptibility of Salmonella and DEC isolates was assessed using the broth dilution method. The detection rates for L. monocytogenes, Salmonella, and DEC in raw livestock meat were 9.06% (228/2, 515), 10.54% (265/2, 515), and 6.16% (155/2, 515), respectively. Pork showed the highest contamination rates for Salmonella and DEC, with prevalence rates of 17.60% (214/1, 216, χ2 = 124.62, p < 0.05) and 7.89% (96/1, 216, χ2 = 14.466, p < 0.05), respectively. L. monocytogenes contamination was notably higher in chilled (14.43%, 84/582) and frozen (12.39%, 55/444) meat than in fresh meat (χ2 = 43.510, p < 0.05). In contrast, Salmonella (12.09%, 180/1489, χ2 = 15.173, p < 0.05) and DEC (7.25%, 108/1489, χ2 = 12.275, p < 0.05) were more prevalent in fresh meat than in chilled or frozen samples. The predominant Salmonella serotypes identified were Salmonella enterica subsp. enterica serovar Typhimurium, followed by Salmonella enterica serovar Derby, Salmonella enterica serovar Rissen, Salmonella enterica serovar London, and Salmonella enterica serotype Enteritidis. Enteroaggregative E. coli was the most frequent pathotype among DEC (84.7%, 133/157), followed by enteropathogenic E. coli (8.3%, 13/157) and enterohemorrhagic E. coli (5.1%, 8/157). Among the 14 tested antimicrobial agents, Salmonella isolates demonstrated an overall resistance rate of 87.50%, while DEC exhibited a resistance rate of 84.70%. Ampicillin and tetracycline showed the highest resistance rates in both pathogens. Multi-drug resistance (MDR) was observed in 67.53% of Salmonella isolates (183 isolates) and 57.96% of DEC isolates (91 isolates). This study highlights the significant contamination of retail raw livestock meat in China by L. monocytogenes, Salmonella, and DEC. The high resistance of MDR in both pathogens poses serious public health risks. Chinese food safety and veterinary authorities should implement stricter measures to control pathogen contamination and regulate the use of antimicrobials in livestock to mitigate these risks.

Background: Several scholarly publications have thoroughly examined the significant role of autophagy in the pathogenesis, progression, and treatment of retinal diseases. This research utilized bibliometric analysis to identify the primary areas of focus and emerging trends within the discipline and offer a comprehensive summary. Methods: The research articles and reviews regarding autophagy and retinal diseases from 2009-01-01 to 2022-12-31 were from the Web of Science Core Collection (WOSCC). The software VOSviewer and CiteSpace were applied to analyze and visualize maps of countries, organizations, authors, journals, keyword networks, and citations in the field of autophagy in retinal diseases. Results: 854 qualified records (721 articles and 133 reviews) were retrieved in this research. The annual publication output of literature shows a growing trend. China is the most productive country, and the author with the most publications is Kai Kaarniranta. Journal Autophagy published the most articles in this field. Keywords analysis can effectively reflect the research hot spots and indicate that diabetic retinopathy and glaucoma have drawn more attention recently. Researchers have shifted the research emphasis on “AMPK”, “angiogenesis”, “mutation”, and “inflammation”. Conclusions: With the bibliometric analysis approach, we presented the number of publications, countries, regions, authors, institutions, keywords, and citations, which further helps researchers understand the hot spots and trends in the field of autophagy in retinal diseases and explore the issues in the rapidly developing area.

BackgroundBeyond the direct effect of COVID-19 infection on young people, the wider impact of the pandemic on other infectious diseases remains unknown. ObjectiveThis study aims to assess changes in the incidence and mortality of 42 notifiable infectious diseases during the pandemic among children and adolescents in China, compared with prepandemic levels. MethodsThe Notifiable Infectious Disease Surveillance System of China was used to detect new cases and fatalities among individuals aged 5-22 years across 42 notifiable infectious diseases spanning from 2018 to 2021. These infectious diseases were categorized into 5 groups: respiratory, gastrointestinal and enterovirus, sexually transmitted and blood-borne, zoonotic, and vector-borne diseases. Each year (2018-2021) was segmented into 4 phases: phase 1 (January 1-22), phase 2 (January 23-April 7), phase 3 (April 8-August 31), and phase 4 (September 1-December 31) according to the varying intensities of pandemic restrictive measures in 2020. Generalized linear models were applied to assess the change in the incidence and mortality within each disease category, using 2018 and 2019 as the reference. ResultsA total of 4,898,260 incident cases and 3701 deaths were included. The overall incidence of notifiable infectious diseases decreased sharply during the first year of the COVID-19 pandemic (2020) compared with prepandemic levels (2018 and 2019), and then rebounded in 2021, particularly in South China. Across the past 4 years, the number of deaths steadily decreased. The incidence of diseases rebounded differentially by the pandemic phase. For instance, although seasonal influenza dominated respiratory diseases in 2019, it showed a substantial decline during the pandemic (percent change in phase 2 2020: 0.21, 95% CI 0.09-0.50), which persisted until 2021 (percent change in phase 4 2021: 1.02, 95% CI 0.74-1.41). The incidence of gastrointestinal and enterovirus diseases decreased by 33.6% during 2020 but rebounded by 56.9% in 2021, mainly driven by hand, foot, and mouth disease (percent change in phase 3 2021: 1.28, 95% CI 1.17-1.41) and infectious diarrhea (percent change in phase 3 2020: 1.22, 95% CI 1.17-1.28). Sexually transmitted and blood-borne diseases were restrained during the first year of 2021 but rebounded quickly in 2021, mainly driven by syphilis (percent change in phase 3 2020: 1.31, 95% CI 1.23-1.40) and gonorrhea (percent change in phase 3 2020: 1.10, 95% CI 1.05-1.16). Zoonotic diseases were not dampened by the pandemic but continued to increase across the study period, mainly due to brucellosis (percent change in phase 2 2020: 0.94, 95% CI 0.75-1.16). Vector-borne diseases showed a continuous decline during 2020, dominated by hemorrhagic fever (percent change in phase 2 2020: 0.68, 95% CI 0.53-0.87), but rebounded in 2021. ConclusionsThe COVID-19 pandemic was associated with a marked decline in notifiable infectious diseases in Chinese children and adolescents. These effects were not sustained, with evidence of a rebound to prepandemic levels by late 2021. To effectively address the postpandemic resurgence of infectious diseases in children and adolescents, it will be essential to maintain disease surveillance and strengthen the implementation of various initiatives. These include extending immunization programs, prioritizing the management of sexually transmitted infections, continuing feasible nonpharmaceutical intervention projects, and effectively managing imported infections.

BackgroundAn accelerated epidemiological transition, spurred by economic development and urbanization, has led to a rapid transformation of the disease spectrum. However, this transition has resulted in a divergent change in the burden of infectious diseases between urban and rural areas. The objective of our study was to evaluate the long-term urban-rural disparities in infectious diseases among children, adolescents, and youths in China, while also examining the specific diseases driving these disparities.Methods and findingsThis observational study examined data on 43 notifiable infectious diseases from 8,442,956 cases from individuals aged 4 to 24 years, with 4,487,043 cases in urban areas and 3,955,913 in rural areas. The data from 2013 to 2021 were obtained from China's Notifiable Infectious Disease Surveillance System. The 43 infectious diseases were categorized into 7 categories: vaccine-preventable, bacterial, gastrointestinal and enterovirus, sexually transmitted and bloodborne, vectorborne, zoonotic, and quarantinable diseases. The calculation of infectious disease incidence was stratified by urban and rural areas. We used the index of incidence rate ratio (IRR), calculated by dividing the urban incidence rate by the rural incidence rate for each disease category, to assess the urban-rural disparity. During the nine-year study period, most notifiable infectious diseases in both urban and rural areas exhibited either a decreased or stable pattern. However, a significant and progressively widening urban-rural disparity in notifiable infectious diseases was observed. Children, adolescents, and youths in urban areas experienced a higher average yearly incidence compared to their rural counterparts, with rates of 439 per 100,000 compared to 211 per 100,000, respectively (IRR: 2.078, 95% CI [2.075, 2.081]; p < 0.001). From 2013 to 2021, this disparity was primarily driven by higher incidences of pertussis (IRR: 1.782, 95% CI [1.705, 1.862]; p < 0.001) and seasonal influenza (IRR: 3.213, 95% CI [3.205, 3.220]; p < 0.001) among vaccine-preventable diseases, tuberculosis (IRR: 1.011, 95% CI [1.006, 1.015]; p < 0.001), and scarlet fever (IRR: 2.942, 95% CI [2.918, 2.966]; p < 0.001) among bacterial diseases, infectious diarrhea (IRR: 1.932, 95% CI [1.924, 1.939]; p < 0.001), and hand, foot, and mouth disease (IRR: 2.501, 95% CI [2.491, 2.510]; p < 0.001) among gastrointestinal and enterovirus diseases, dengue (IRR: 11.952, 95% CI [11.313, 12.628]; p < 0.001) among vectorborne diseases, and 4 sexually transmitted and bloodborne diseases (syphilis: IRR 1.743, 95% CI [1.731, 1.755], p < 0.001; gonorrhea: IRR 2.658, 95% CI [2.635, 2.682], p < 0.001; HIV/AIDS: IRR 2.269, 95% CI [2.239, 2.299], p < 0.001; hepatitis C: IRR 1.540, 95% CI [1.506, 1.575], p < 0.001), but was partially offset by lower incidences of most zoonotic and quarantinable diseases in urban areas (for example, brucellosis among zoonotic: IRR 0.516, 95% CI [0.498, 0.534], p < 0.001; hemorrhagic fever among quarantinable: IRR 0.930, 95% CI [0.881, 0.981], p = 0.008). Additionally, the overall urban-rural disparity was particularly pronounced in the middle (IRR: 1.704, 95% CI [1.699, 1.708]; p < 0.001) and northeastern regions (IRR: 1.713, 95% CI [1.700, 1.726]; p < 0.001) of China. A primary limitation of our study is that the incidence was calculated based on annual average population data without accounting for population mobility.ConclusionsA significant urban-rural disparity in notifiable infectious diseases among children, adolescents, and youths was evident from our study. The burden in urban areas exceeded that in rural areas by more than 2-fold, and this gap appears to be widening, particularly influenced by tuberculosis, scarlet fever, infectious diarrhea, and typhus. These findings underscore the urgent need for interventions to mitigate infectious diseases and address the growing urban-rural disparity.

To explore the predictive value of thyroid function in severe aplastic anemia (SAA) patients treated with immunosuppressive therapy (IST), 149 SAA patients in our center were enrolled between February 2015 and June 2020 in this study. We assessed the thyroid function of 134 patients without primary thyroid diseases, and discovered that 89 patients were accompanied by abnormal thyroid hormone, especially low triiodothyronine (T3). Patients with higher pretreatment-free T3 (FT3) levels (>5 pmol/L) demonstrated superior response rates at 3 and 6 months after IST compared to those with lower FT3 levels (54.5% vs 35.4%, P = .020; 67.3% vs 46.9%, P = .020). Multivariate analysis indicated that shorter disease duration (≤56 days) and response at 6 months were independent favorable factors of overall survival (relative risk [RR] = 2.66, 95% confidence interval [CI] = 1.03–6.90, P = .040; RR = 30.10, 95% CI = 4.02–225.66, P = .001). The 6-year failure-free survival (FFS) was 53.8% (95% CI = 40.9%–65.1%). Multivariate analysis revealed that patients with a response at 6 months, shorter duration (≤56 days) and receiving rabbit antithymocyte globulin (ATG) had better FFS outcomes than those without a response at 6 months, with a longer duration and receiving porcine ATG (RR = 22.6, 95% CI = 7.9–64.9, P < .001; RR = 2.4, 95% CI = 1.3–4.5, P = .006; RR = 2.5, 95% CI = 1.1–5.8, P = .030). In conclusion, FT3 levels reflect the severity of SAA, and patients with higher FT3 levels (>5 pmol/L) had superior response rates than those with lower ones.

Abstract This article theorises the local world as a conceptual scaffold for future conservation and regeneration. It aims to catalyse a theoretical dialogue across the East and West to understand how ordinary places and lifeworlds are preserved, reproduced, and possibly reimagined. The local worlds discussed herein are conceptualised as the worlds of many, the worlds of relating, the worlds of structuring and the worlds of becoming. These four cardinal points present a source of open-endedness and futurity for contemporary architectural reinterpretation. The current article examines the characterisation of the Wen village conservation and regeneration project, led by the Amateur Architecture Studio in Zhejiang Province of China (2012–2016), as an architectural reimagination of local worlds, with a strong sensitivity to the ordinary places and lifeworlds of rural China and juxtapositions of new local worlds within old worlds. By piecing together the flows and fragments of the architectural process, this article shows how locally situated designs and dynamics have shaped the project in both its formation and afterlife, both ethically and contemporarily. Using close readings of popular and oral accounts from both architect’s and users’ perspectives, this article extends the case study by broadening theoretical conversations about contemporary architecture’s capacity to reimagine local worlds.

Abstract Background Respiratory infectious diseases (RIDs) remain a pressing public health concern, posing a significant threat to the well-being and lives of individuals. This study delves into the incidence of seven primary RIDs during the period 2017–2021, aiming to gain deeper insights into their epidemiological characteristics for the purpose of enhancing control and prevention strategies. Methods Data pertaining to seven notifiable RIDs, namely, seasonal influenza, pulmonary tuberculosis (PTB), mumps, scarlet fever, pertussis, rubella and measles, in the mainland of China between 2017 and 2021 were obtained from the National Notifiable Disease Reporting System (NNDRS). Joinpoint regression software was utilized to analyze temporal trends, while SaTScan software with a Poisson probability model was used to assess seasonal and spatial patterns. Results A total of 11,963,886 cases of the seven RIDs were reported during 2017–2021, and yielding a five-year average incidence rate of 170.73 per 100,000 individuals. Among these RIDs, seasonal influenza exhibited the highest average incidence rate (94.14 per 100,000), followed by PTB (55.52 per 100,000), mumps (15.16 per 100,000), scarlet fever (4.02 per 100,000), pertussis (1.10 per 100,000), rubella (0.59 per 100,000), and measles (0.21 per 100,000). Males experienced higher incidence rates across all seven RIDs. PTB incidence was notably elevated among farmers and individuals aged over 65, whereas the other RIDs primarily affected children and students under 15 years of age. The incidences of PTB and measles exhibited a declining trend from 2017 to 2021 (APC = −7.53%, P = 0.009; APC = −40.87%, P = 0.02), while the other five RIDs peaked in 2019. Concerning seasonal and spatial distribution, the seven RIDs displayed distinct characteristics, with variations observed for the same RIDs across different regions. The proportion of laboratory-confirmed cases fluctuated among the seven RIDs from 2017 to 2021, with measles and rubella exhibiting higher proportions and mumps and scarlet fever showing lower proportions. Conclusions The incidence of PTB and measles demonstrated a decrease in the mainland of China between 2017 and 2021, while the remaining five RIDs reached a peak in 2019. Overall, RIDs continue to pose a significant public health challenge. Urgent action is required to bolster capacity-building efforts and enhance control and prevention strategies for RIDs, taking into account regional disparities and epidemiological nuances. With the rapid advancement of high-tech solutions, the development and effective implementation of a digital/intelligent RIDs control and prevention system are imperative to facilitate precise surveillance, early warnings, and swift responses. Graphical Abstract

Abstract Background Previous studies have verified the dysfunction of mesenchymal stem cells (MSCs) for immunoregulation in acquired aplastic anemia (AA) patients. Exosomes derived from MSCs can partially substitute MSCs acting as immune regulator. Dysfunction of exosomes (Exos) derived from AA-MSC (AA-Exos) may play a key role in immunologic dissonance. Method In this study, CD3 + T cells were collected and cocultured with AA-Exos and exosomes derived from HD-MSC (HD-Exos). The proliferation, differentiation and activation of CD3 + T cells were detected to compare the immunosuppressive effects between AA-Exos and HD-Exos. An immune-mediated murine model of AA was structured to compare the therapeutic effect of AA-Exos and HD-Exos. Furthermore, total RNA including miRNA from exosomes we purified and total RNA of CD3 + T cells were extracted for RNA-seq in order to construct the miRNA–mRNA network for interactions and functional analysis. Results AA-Exos had impaired inhibition effects on CD3 + T cells in terms of cell proliferation, activation and differentiation compared with exosomes from HD-Exos. HD-Exos showed a more effective rescue of AA mice compared to AA-Exos. Importantly, we found some differentially expressed miRNA involved in immune response, such as miR-199, miR-128 and miR-486. The Gene Ontology analysis of differentially expressed genes (DEGs) revealed involvement of various cellular processes, such as lymphocyte chemotaxis, lymphocyte migration and response to interferon-gamma. The Kyoto Encyclopedia of Genes and Genomes analysis illustrated upregulation of critical pathways associated with T cell function after coculturing with AA-Exos compared with HD-Exos, such as graft-versus-host disease, Th17 cell differentiation and JAK-STAT signaling pathway. A miRNA–mRNA network was established to visualize the interaction between them. Conclusion In summary, AA-Exos had impaired immunosuppressive effect on T cells, less ability to rescue AA mice and differently expressed miRNA profile, which might partly account for the pathogenesis of AA as well as provide a new target of AA treatment.

To tackle the complexity and limited applicability of high-precision segmentation models for damaged road markings, this study proposes a Multi-level Adaptive Lightweight Network (MALNet) based on knowledge distillation. By incorporating multi-scale dilated convolution and adaptive spatial channel attention fusion modules, the MALNet model significantly enhances the precision, integrity, and robustness of its segmentation branch. Furthermore, it employs an intricate knowledge distillation strategy, channeling rich, layered insights from a teacher model to a student model, thus elevating the latter’s segmentation ability. Concurrently, it streamlines the student model by markedly reducing its parameter count and computational demands, culminating in a segmentation network that is both high-performing and pragmatic. Rigorous testing on three distinct data sets for damaged road marking detection—CDM_P (Collective Damaged road Marking—Public), CDM_H (Collective Damaged road Marking—Highways), and CDM_C (Collective Damaged road Marking—Cityroad)—underscores the MALNet model’s superior segmentation abilities across all damage types, outperforming competing models in accuracy and completeness. Notably, the MALNet model excels in parameter efficiency, computational economy, and throughput. After distillation, the student model’s parameters and computational load decrease to only 31.78% and 27.40% of the teacher model’s, respectively, while processing speeds increase to 1.9 times, demonstrating a significant improvement in lightweight design.

Abstract Background Recently, attention has focused on the impact of global climate change on infectious diseases. Storm flooding is an extreme weather phenomenon that not only impacts the health of the environment but also worsens the spread of pathogens. This poses a significant challenge to public health security. However, there is still a lack of research on how different levels of storm flooding affect susceptible enteric infectious diseases over time. Methods Data on enteric infectious diseases, storm flooding events, and meteorology were collected for Changsha, Hunan Province, between 2016 and 2020. The Wilcoxon Rank Sum Test was used to identify the enteric infectious diseases that are susceptible to storm flooding. Then, the lagged effects of different levels of storm flooding on susceptible enteric infectious diseases were analyzed using a distributed lag nonlinear model. Results There were eleven storm flooding events in Changsha from 2016 to 2020, concentrated in June and July. 37,882 cases of enteric infectious diseases were reported. During non-flooding days, the daily incidence rates of typhoid/paratyphoid and bacillary dysentery were 0.3/100,000 and 0.1/100,000, respectively. During flooding days, the corresponding rates increased to 2.0/100,000 and 0.8/100,000, respectively. The incidence rates of both diseases showed statistically significant differences between non-flooding and flooding days. Correlation analysis shows that the best lags for typhoid/paratyphoid and bacillary dysentery relative to storm flooding events may be 1 and 3 days. The results of the distributed lag nonlinear model showed that typhoid/paratyphoid had the highest cumulative RR values of 2.86 (95% CI: 1.71–4.76) and 8.16 (95% CI: 2.93–22.67) after 4 days of general flooding and heavy flooding, respectively; and bacillary dysentery had the highest cumulative RR values of 1.82 (95% CI: 1.40–2.35) and 3.31 (95% CI: 1.97–5.55) after 5 days of general flooding and heavy flooding, respectively. Conclusions Typhoid/paratyphoid and bacillary dysentery are sensitive enteric infectious diseases related to storm flooding in Changsha. There is a lagging effect of storm flooding on the onset of typhoid/paratyphoid and bacillary dysentery, with the best lagging periods being days 1 and 3, respectively. The cumulative risk of typhoid/paratyphoid and bacillary dysentery was highest at 4/5 days lag, respectively. The higher of storm flooding, the higher the risk of disease, which suggests that the authorities should take appropriate preventive and control measures before and after storm flooding.

ObjectiveTo explore the impact of extreme weather events on circulatory system disease mortality among residents in Changsha city , Hunan province from 2015 through 2019 for providing evidence to prevention and control and early warning of circulatory system diseases. Methods Daily number of circulatory disease mortality among residents of Changsha city were collected from Changsha Municipal Center for Disease Control and Prevention for the period of 2015 – 2019. Population data and meteorological data of the same period were simultaneously collected from Hunan Provincial Bureau of Statistics and China Meteorological Data Network. The association of extreme weather events with circulatory disease mortality in the population was analyzed with U-test of Poisson distribution, Spearman correlation analysis and single lag effect analysis. ResultsFollowing extreme weather events were identified during the 5 year period for the city: 72 low temperature and cold wave events occurring in winter season (between January and February and December of each year), 14 heatwave events in summer season (between July and August of each year), and 21 rainy and sunless weather events occurring throughout a year. During the period, totally 123 626 circulatory disease deaths were reported in the city, including 9 865, 5 286 and 14 093 deaths occurred under extreme weather conditions of low temperature and cold wave, high temperature and heat wave, and rainy and sunless weather, respectively. The daily total number of circulatory disease mortality was positively correlated with the occurrence of low temperature and cold wave (r = 0.138), high temperature and heat wave (r = 0.114), and sunless weather (r = 0.097) (all P < 0.01). The lag effect of high temperature and heat wave and rainy and sunless weather on daily number of circulatory disease mortality was not obvious. There was a single-lag effect of low temperature and cold wave on daily number of circulatory disease mortality, with a strong effect at lag day 2 – lag day 4 and the strongest hysteresis effect at lag day 2 (cross-correlation coefficient = 0.161). The single-lag effect of daily minimum temperature in cold season on daily number of circulatory disease mortality was the most obvious and the effect was the strongest at lag day 7 (correlation coefficient = – 0.518). The effect of low temperature and cold wave was the most obvious at lag day 2. ConclusionFrom 2015 to 2019, extreme weather events in Changsha were associated with circulatory disease mortality, among which low temperature and cold snaps had the greatest impact, and there was a significant single-day lag effect on daily number of circulatory disease mortality.

Abstract Background Acute diarrhea with fever can potentially represent a more severe form of the disease compared to non-febrile diarrhea. This study was to investigate the epidemiological characteristics and enteric pathogen composition of febrile-diarrheal patients, and to explore factors including pathogens associated with fever by age group. Methods A nationwide surveillance study of acute diarrheal patients of all ages was conducted in 217 sentinel hospitals from 31 provinces (autonomous regions or municipalities) in China between 2011 and 2020. Seventeen diarrhea-related pathogens, including seven viruses and ten bacteria, were investigated and their association with occurrence of fever symptoms was assessed using multivariate logistic analysis. Results A total of 146,296 patients with acute diarrhea (18.6% with fever) were tested. Th diarrheal children below 5 years had the highest frequency of fever (24.2%), and related to significantly higher prevalence of viral enteropathogens (40.2%) as compared with other age groups (P

Summary: Background: Voiding cystourethrography (VCUG) is the gold standard for the diagnosis and grading of vesicoureteral reflux (VUR). However, VUR grading from voiding cystourethrograms is highly subjective with low reliability. This study aimed to develop a deep learning model to improve reliability for VUR grading on VCUG and compare its performance to that of clinicians. Methods: In this retrospective study in China, VCUG images were collected between January 2019 and September 2022 from our institution as an internal dataset for training and 4 external data sets as external testing set for validation. Samples were divided into training (N = 1000) and validation sets (N = 500), internal testing set (N = 168), and external testing set (N = 280). An ensemble learning-based model, Deep-VCUG, using Res-Net 101 and the voting methods was developed to predict VUR grade. The grading performance was assessed using heatmaps, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, and F1 score in the internal and external testing set. The performances of four clinicians (2 pediatric urologists and 2 radiologists) with and without the Deep-VCUG assisted to predict VUR grade were explored in external testing sets. Findings: A total of 1948 VCUG images were collected (Internal dataset = 1668; multi-center external dataset = 280). For assessing unilateral VUR grading, the Deep-VCUG achieved AUCs of 0.962 (95% confidence interval [CI]: 0.943–0.978) and 0.944 (95% [CI]: 0.921–0.964) in the internal and external testing sets, respectively, for bilateral VUR grading, the Deep-VCUG also achieved high AUCs of 0.960 (95% [CI]: 0.922–0.983) and 0.924 (95% [CI]: 0.887–0.957). The Deep-VCUG model using voting method outperformed single model and clinician in terms of classification based on VCUG image. Moreover, Under the Dee-VCUG assisted, the classification ability of junior and senior clinicians was significantly improved. Interpretation: The Deep-VCUG model is a generalizable, objective, and accurate tool for vesicoureteral reflux grading based on VCUG imaging and had good assistance with clinicians to VUR grading applicability. Funding: This study was supported by Natural Science Foundation of China, “Fuqing Scholar” Student Scientific Research Program of Shanghai Medical College, Fudan University, and the Program of Greater Bay Area Institute of Precision Medicine (Guangzhou).

Abstract Background For the unclear pathogenesis of Sjogren's syndrome (SS), further exploration is necessary. Mesenchymal stem cells (MSCs) and derived exosomes (MSCs‐exo) have exhibited promising results in treating SS. Object This study aimed to investigate the effect and mechanism of human umbilical cord MSCs (UC‐MSCs) on SS. Methods Nonobese Diabetic (NOD) mouse splenic T cells were co‐cultured with UC‐MSCs and UC‐MSCs‐exo, and interferon‐gamma (IFN‐γ), interleukin (IL)‐6, IL‐10, prostaglandin E2 (PGE2), and transforming growth factor‐β1 (TGF‐β1) levels in the supernatant were assessed by quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. Co‐cultured T cells were injected into NOD mice via the tail vein. The inflammatory cell infiltration in the intestine and the submandibular gland was characterized by hematoxylin‐eosin staining. Treg/Th17 homeostasis within the spleen was determined by flow cytometry. Gut microbiota was detected by 16S rRNA sequencing, and the relationship between differential microbiota and Treg/Th17 cytokines was analyzed by the Pearson correlation coefficient. Results UC‐MSCs, UC‐MSCs‐exo, and NOD mouse splenic T cells were successfully cultured and identified. After T cells were co‐cultured with UC‐MSCs and UC‐MSCs‐exo, both IFN‐γ and IL‐6 were decreased while IL‐10, PGE2, and TGF‐β1 were increased in transcriptional and translational levels. UC‐MSCs and UC‐MSCs‐exo partially restored salivary secretion function, reduced Ro/SSA antibody and α‐Fodrin immunoglobulin A levels, reduced inflammatory cell infiltration in the intestine and submandibular gland, raised proportion of Treg cells, decreased IFN‐γ, IL‐6, IL‐2, IL‐17, lipopolysaccharide, and tumor necrosis factor‐alpha levels, and raised IL‐10, Foxp3, and TGF‐β1 levels by affecting co‐cultured T cells. The intervention of UC‐MSCs and UC‐MSCs‐exo improved intestinal homeostasis in NOD mice by increasing microbiota diversity and richness. Additionally, differential microbiota was significantly associated with Treg/Th17 cytokine levels. Conclusion Human UC‐MSCs and UC‐MSCs‐exo improved disease characterization of SS in NOD mice through regulation of gut microbiota and Treg/Th17 cellular immunity.

PurposeLaparoscopic partial nephrectomy (LPN) remains the most commonly used measure for treating localized renal cell cancer (RCC) with an increasing incidence of RCC ever since the 1990s. This study aimed to identify risk factors that affect the postoperative time of drainage and total drainage volume after LPN.MethodThe clinical data of 612 RCC patients who received LPN from January 2012 to December 2022 in our hospital, including the postoperative drainage time and total drainage volume, were retrospectively analyzed. Univariable and multivariable linear regression and correlation analyses were used to identify the correlations between 21 factors, which include gender, age, history of alcohol consumption, family history of RCC, body weight, body mass index (BMI), and operation time, postoperative drainage time, and total drainage volume.ResultsThe mean time of drainage was 3.52 ± 0.71 days (range: 2 to 8 days), with an average total drainage volume of 259.83 ± 72.64 mL (range: 50 to 620 mL). Both univariable and multivariable linear regression analyses revealed several statistically significant associations. Gender (p = 0.04), age (p = 0.008), smoking history (p

Abstract Background Deep learning has been extensively used in digital histopathology. The purpose of this study was to test deep learning (DL) algorithms for predicting the vital status of whole-slide image (WSI) of uveal melanoma (UM). Methods We developed a deep learning model (Google-net) to predict the vital status of UM patients from histopathological images in TCGA-UVM cohort and validated it in an internal cohort. The histopathological DL features extracted from the model and then were applied to classify UM patients into two subtypes. The differences between two subtypes in clinical outcomes, tumor mutation, and microenvironment, and probability of drug therapeutic response were investigated further. Results We observed that the developed DL model can achieve a high accuracy of > = 90% for patches and WSIs prediction. Using 14 histopathological DL features, we successfully classified UM patients into Cluster1 and Cluster2 subtypes. Compared to Cluster2, patients in the Cluster1 subtype have a poor survival outcome, increased expression levels of immune-checkpoint genes, higher immune-infiltration of CD8 + T cell and CD4 + T cells, and more sensitivity to anti-PD-1 therapy. Besides, we established and verified prognostic histopathological DL-signature and gene-signature which outperformed the traditional clinical features. Finally, a well-performed nomogram combining the DL-signature and gene-signature was constructed to predict the mortality of UM patients. Conclusions Our findings suggest that DL model can accurately predict vital status in UM patents just using histopathological images. We found out two subgroups based on histopathological DL features, which may in favor of immunotherapy and chemotherapy. Finally, a well-performing nomogram that combines DL-signature and gene-signature was constructed to give a more straightforward and reliable prognosis for UM patients in treatment and management.

Abstract Background Typhoid fever and paratyphoid fever are one of the most criticial public health issues worldwide, especially in developing countries. The incidence of this disease may be closely related to socio-economic factors, but there is a lack of research on the spatial level of relevant determinants of typhoid fever and paratyphoid fever. Methods In this study, we took Hunan Province in central China as an example and collected the data on typhoid and paratyphoid incidence and socio-economic factors in 2015–2019. Firstly spatial mapping was made on the disease prevalence, and again using geographical probe model to explore the critical influencing factors of typhoid and paratyphoid, finally employing MGWR model to analysis the spatial heterogeneity of these factors. Results The results showed that the incidence of typhoid and paratyphoid fever was seasonal and periodic and frequently occurred in summer. In the case of total typhoid and paratyphoid fever, Yongzhou was the most popular, followed by Xiangxi Tujia and Miao Autonomous Prefecture, Huaihua and Chenzhou generally focused on the south and west. And Yueyang, Changde and Loudi had a slight increase trend year by year from 2015 to 2019. Moreover, the significant effects on the incidence of typhoid and paratyphoid fever from strong to weak were as follows: gender ratio(q = 0.4589), students in ordinary institutions of higher learning(q = 0.2040), per capita disposable income of all residents(q = 0.1777), number of foreign tourists received(q = 0.1697), per capita GDP(q = 0.1589), and the P values for these factors were less than 0.001. According to the MGWR model, gender ratio, per capita disposable income of all residents and Number of foreign tourists received had a positive effect on the incidence of typhoid and paratyphoid fever. In contrast, students in ordinary institutions of higher learning had a negative impact, and per capita GDP shows a bipolar change. Conclusions The incidence of typhoid and paratyphoid fever in Hunan Province from 2015 to 2019 was a marked seasonality, concentrated in the south and west of Hunan Province. Attention should be paid to the prevention and control of critical periods and concentrated areas. Different socio-economic factors may show other directions and degrees of action in other prefecture-level cities. To summarize, health education, entry-exit epidemic prevention and control can be strengthened. This study may be beneficial to carry out targeted, hierarchical and focused prevention and control of typhoid fever and paratyphoid fever, and provide scientific reference for related theoretical research.

Abstract Background Certain bacterial infectious diseases are categorized as notifiable infectious diseases in China. Understanding the time-varying epidemiology of bacterial infections diseases can provide scientific evidence to inform prevention and control measures. Methods Yearly incidence data for all 17 major notifiable bacterial infectious diseases (BIDs) at the province level were obtained from the National Notifiable Infectious Disease Reporting Information System in China between 2004 and 2019. Of them 16 BIDs are divided into four categories, respiratory transmitted diseases (RTDs, 6 diseases), direct contact/fecal-oral transmitted diseases (DCFTDs, 3 diseases), blood-borne/sexually transmitted diseases (BSTDs, 2 diseases), and zoonotic and vector-borne diseases (ZVDs, 5 diseases), and neonatal tetanus is excluded in the analysis. We characterized the demographic, temporal, and geographical features of the BIDs and examined their changing trends using a joinpoint regression analysis. Results During 2004‒2019, 28 779 thousand cases of BIDs were reported, with an annualized incidence rate of 134.00 per 100 000. RTDs were the most commonly reported BIDs, accounting for 57.02% of the cases (16 410 639/28 779 000). Average annual percent changes (AAPC) in incidence were − 1.98% for RTDs, − 11.66% for DCFTDs, 4.74% for BSTDs, and 4.46% for ZVDs. Females had a higher incidence of syphilis than males, and other BIDs were more commonly reported in males. Among 0-5-year-olds, the diseases with the largest increases in incidence were pertussis (15.17% AAPC) and scarlet fever (12.05%). Children and students had the highest incidence rates of scarlet fever, pertussis, meningococcal meningitis, and bacillary dysentery. Northwest China had the highest incidence of RTDs, while South and East China had the highest incidences of BSTDs. Laboratory confirmation of BIDs increased from 43.80 to 64.04% during the study period. Conclusions RTDs and DCFTDs decreased from 2004 to 2019 in China, while BSTDs and ZVDs increased during the same period. Great attention should be paid to BSTDs and ZVDs, active surveillance should be strengthened, and timely control measures should be adopted to reduce the incidence.

It is a challenging task to accurately segment damaged road markings from images, mainly due to their fragmented, dense, small-scale, and blurry nature. This study proposes a multi-scale spatial kernel selection net named M-SKSNet, a novel model that integrates a transformer and a multi-dilated large kernel convolutional neural network (MLKC) block to address these issues. Through integrating multiple scales of information, the model can extract high-quality and semantically rich features while generating damage-specific representations. This is achieved by leveraging both the local and global contexts, as well as self-attention mechanisms. The performance of M-SKSNet is evaluated both quantitatively and qualitatively, and the results show that M-SKSNet achieved the highest improvement in F1 by 3.77% and in IOU by 4.6%, when compared to existing models. Additionally, the effectiveness of M-SKSNet in accurately extracting damaged road markings from images in various complex scenarios (including city roads and highways) is demonstrated. Furthermore, M-SKSNet is found to outperform existing alternatives in terms of both robustness and accuracy.

This study identified 13 GhTIR1/AFB members in G. hirsutum through bioinformatics methods and divided them into three subgroups by phylogenetic tree analysis. Motif and gene structure analysis showed that the genes in this family were highly conserved. Promoter cis-acting element analysis found that the promoters of GhTIR1/AFBs contained a large number of cis-acting elements in response to growth and development and abiotic stress. Further RT-qPCR results showed that GhTIR1/AFB genes responded to various abiotic stresses such as IAA, ABA, cold, and heat, and the expression levels of each gene changed obviously, especially Gh_D08G0763 (GhTIR1), which responded significantly to cold injury. Using VIGS (virus-induced gene silencing) technology to silence Gh_D08G0763 in the cold-tolerant cotton variety ZM36, it was found that the resistance of ZM36 to cold damage was significantly reduced. The physiological response mechanism of the Gh_D08G0763 in resisting cold damage was further analyzed through trypan blue staining of leaves and determination of enzyme activity levels. This study provided effective genetic resources for cotton cold-tolerance breeding.

Background Animal experiments and clinical trials have revealed a potential relationship between sleep disorders and asthma. However, the associations between these factors remain unclear.Material and methods We searched PubMed, Embase, Web of Science and Cochrane Library databases for eligible studies published before 30 December 2022. Studies investigating the association between sleep disorders (insomnia, poor sleep quality and insufficient sleep time) and asthma were selected. Sleep disorders were assessed using questionnaires, interviews, or medical records. Asthma was diagnosed based on medical history and drug use. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality checklist were employed for quality assessment. We used OR with 95% CI as the effect measures and forest plots to display the results. Heterogeneity was evaluated using I2 statistics and subgroup analyses were performed for bias analysis. Publication bias was evaluated using the funnel plots and Egger’s test.Results Twenty-three studies were included in the primary analysis, which suggested a positive association between sleep disorders and asthma (OR: 1.38, 95% CI 1.10 to 1.74). Subgroup analyses were conducted according to the study design, age, family history of asthma and type of sleep disorders. We did not find any association between sleep disorders and asthma in children aged ˂12 years (OR: 1.13, 95% CI 0.97 to 1.32). The association was insignificant in studies where the family history of asthma was adjusted for (OR: 1.16, 95% CI 0.94 to 1.42). Funnel plot and Egger’s test indicated a significant publication bias.Conclusion Sleep disorders are associated with an increased prevalence and incidence of asthma. However, the quality of the evidence was low because of potential biases.PROSPERO registration number CRD42023391989.

Summary: DEAH-Box Helicase 38 (DHX38) is a pre-mRNA splicing factor and also a disease-causing gene of autosomal recessive retinitis pigmentosa (arRP). The role of DHX38 in the development and maintenance of the retina remains largely unknown. In this study, by using the dhx38 knockout zebrafish model, we demonstrated that Dhx38 deficiency causes severe differentiation defects and apoptosis of retinal progenitor cells (RPCs) through disrupted mitosis and increased DNA damage. Furthermore, we found a significant accumulation of R-loops in the dhx38-deficient RPCs and human cell lines. Finally, we found that DNA replication stress is the prerequisite for R-loop-induced DNA damage in the DHX38 knockdown cells. Taken together, our study demonstrates a necessary role of DHX38 in the development of retina and reveals a DHX38/R-loop/replication stress/DNA damage regulatory axis that is relatively independent of the known functions of DHX38 in mitosis control.

Abstract Dynamic processes that occur on the edge of complex networks are relevant to a variety of real-world systems, where states are defined on individual edges, and nodes are active components with information processing capabilities. In traditional studies of edge controllability, all adjacent edge states are assumed to be coupled. In this paper, we release this all-to-all coupling restriction and propose a general edge dynamics model. We give a theoretical framework to study the structural controllability of the general edge dynamics and find that the set of driver nodes for edge controllability is unique and determined by the local information of nodes. Applying our framework to a large number of model and real networks, we find that there exist lower and upper bounds of edge controllability, which are determined by the coupling density, where the coupling density is the proportion of adjacent edge states that are coupled. Then we investigate the proportion of effective coupling in edge controllability and find that homogeneous and relatively sparse networks have a higher proportion, and that the proportion is mainly determined by degree distribution. Finally, we analyze the role of edges in edge controllability and find that it is largely encoded by the coupling density and degree distribution, and are influenced by in- and out-degree correlation.

Due to magnetic gearing effects, spoke-type permanent magnet vernier machines (ST-PMVMs) have the merit of high torque density, where an extra torque amplification coefficient, i.e., pole ratio (the pole-pair ratio of PMs to armature windings) is introduced. However, different from surface-mounted PMVM, the variation of torque against pole ratio in ST-PMVMs is non-linear, which is increased at first and then decreased. This article is devoted to identify the optimal pole ratio of ST-PMVMs by equivalent magnetic circuit model. It is found that except the P r th air-gap magnetomotive force (MMF) harmonic having the same pole-pair of PM, the Pa th air-gap MMF harmonic having the same pole-pair of armature winding is also induced due to the modulation of doubly salient air-gap structure. The P r th MMF harmonic produces positive torque, while Pa th MMF harmonic produces negative torque. With the increase of pole ratio, the proportion of Pa th MMF harmonic as well as negative torque is increased, which reduces the advantages of high pole ratio coefficient. Further, the influence of dimension parameters on the performance of ST-PMVMs under different pole ratio are investigated. Results show that ST-PMVMs with pole ratio 2.6 have high torque density, low cogging torque and high power factor simultaneously. Finally, a prototype is manufactured to validate the analysis.

Abstract Mutations in TUB-like protein 1 (TULP1) are associated with severe early-onset retinal degeneration in humans. However, the pathogenesis remains largely unknown. There are two homologous genes of TULP1 in zebrafish, namely tulp1a and tulp1b. Here, we generated the single knockout (tulp1a −/− and tulp1b −/− ) and double knockout (tulp1-dKO) models in zebrafish. Knockout of tulp1a resulted in the mislocalization of UV cone opsins and the degeneration of UV cones specifically, while knockout of tulp1b resulted in mislocalization of rod opsins and rod-cone degeneration. In the tulp1-dKO zebrafish, mislocalization of opsins was present in all types of photoreceptors, and severe degeneration was observed at a very early age, mimicking the clinical manifestations of TULP1 patients. Photoreceptor cilium length was significantly reduced in the tulp1-dKO retinas. RNA-seq analysis showed that the expression of tektin2 (tekt2), a ciliary and flagellar microtubule structural component, was downregulated in the tulp1-dKO zebrafish. Dual-luciferase reporter assay suggested that Tulp1a and Tulp1b transcriptionally activate the promoter of tekt2. In addition, ferroptosis might be activated in the tulp1-dKO zebrafish, as suggested by the up-regulation of genes related to the ferroptosis pathway, the shrinkage of mitochondria, reduction or disappearance of mitochondria cristae, and the iron and lipid droplet deposition in the retina of tulp1-dKO zebrafish. In conclusion, our study establishes an appropriate zebrafish model for TULP1-associated retinal degeneration and proposes that loss of TULP1 causes defects in cilia structure and opsin trafficking through the downregulation of tekt2, which further increases the death of photoreceptors via ferroptosis. These findings offer insight into the pathogenesis and clinical treatment of early-onset retinal degeneration.

Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren ‘s syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod’s unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.

IntroductionRecently the role of gut microbial dysbiosis in many ocular disorders, including but not limited to uveitis, age-related macular degeneration (AMD), diabetic retinopathy (DR), dry eye, keratitis and orbitopathy is a hot research topic in the field. Targeting gut microbiota to treat these diseases has become an unstoppable trend. Bibliometric study and visualization analysis have become essential methods for literature analysis in the medical research field. We aim to depict this area's research hotspots and future directions by bibliometric software and methods.MethodsWe search all the related publications from the Web of Science Core Collection. Then, CiteSpace was applied to analyze and visualize the country distributions, dual-map overlay of journals, keyword bursts, and co-cited references. VOSviewer was employed to identify authors, co-cited authors, journals and co-cited journals and display the keyword co-occurrence networks.ResultsA total of 284 relevant publications were identified from 2009 to 2023. The number of studies has been small in the first five years and has grown steadily since 2016. These studies were completed by 1,376 authors from 41 countries worldwide, with the United States in the lead. Lin P has published the most papers while Horai R is the most co-cited author. The top journal and co-cited journal are both Investigative Ophthalmology & Visual Science. In the keyword co-occurrence network, except gut microbiota, inflammation becomes the keyword with the highest frequency. Co-citation analyses reveal that gut dysbiosis is involved in common immune- and inflammation-mediated eye diseases, including uveitis, diabetic retinopathy, age-related macular degeneration, dry eye, and Graves' orbitopathy, and the study of microbiomes is no longer limited to the bacterial populations. Therapeutic strategies that target the gut microbiota, such as probiotics, healthy diet patterns, and fecal microbial transplantation, are effective and critical to future research.ConclusionsIn conclusion, the bibliometric analysis displays the research hotspots and developmental directions of the involvement of gut microbiota in the pathogenesis and treatment of some ocular diseases. It provides an overview of this field's dynamic evolution and structural relationships.

Abstract Background To quantitatively assess the impact of the onset-to-diagnosis interval (ODI) on severity and death for coronavirus disease 2019 (COVID-19) patients. Methods This retrospective study was conducted based on the data on COVID-19 cases of China over the age of 40 years reported through China’s National Notifiable Infectious Disease Surveillance System from February 5, 2020 to October 8, 2020. The impacts of ODI on severe rate (SR) and case fatality rate (CFR) were evaluated at individual and population levels, which was further disaggregated by sex, age and geographic origin. Results As the rapid decline of ODI from around 40 days in early January to

Abstract Background Combining immune checkpoint inhibitors with chemotherapy can synergistically improve antitumor activity and are generally well tolerated. Recently, the efficacy and safety of combination therapy has been demonstrated for many cancers, including urothelial carcinomas. The aim of this retrospective pilot study was to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line adjuvant treatment for locally advanced or metastatic bladder cancer. Methods We conducted a retrospective analysis of 31 patients with locally advanced or metastatic bladder cancer from December 2020 to January 2022 with an Eastern Cooperative Oncology Group performance status of 0/1. Of the 31 patients, 14 patients received tislelizumab (200 mg i.v. every 3 weeks, Q3W) plus 21 days cycles of chemotherapy (gemcitabine, 1000 mg/m2 i.v. on days 1 and 8 of each cycle + cisplatin, 70 mg/m2 i.v. on day 2 of each cycle) (TGC) treatment and 17 patients received gemcitabine plus cisplatin chemotherapy (GC) treatment. All patients treated with bladder cytoreductive surgery and were treated for four 21 days cycles until disease progression or intolerable treatment-related adverse events (TRAEs). The objective progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR) and TRAEs were recorded and reviewed. Results As of the cut-off date (March 25, 2022), PFS, OS, ORR, DCR, CBR and TRAEs were evaluated in 14 patients receiving combination therapy and 17 patients in the chemotherapy alone group. The median PFS was 36.0 [95% confidence interval (CI) 33.1–38.9] weeks in the TGC group and 29.0 (95% CI 25.4–32.6) weeks in the GC group [hazard ratio (HR) 0.15 (95% CI 0.04–0.55)]. In the GC group, the median OS was 48.0 (95% CI 39.7–56.3) weeks; the median OS was not yet mature for the TGC group [HR 0.26 (95% CI 0.07–0.94)]. Treatment with TGC resulted in improved DCR (TGC 71.4%; GC 65.0%) and CBR (TGC 64.3%; GC 52.9%) compared with GC. However, although higher incidences of grade ≥ 3 TRAEs were observed with TGC compared with GC (35.7% vs 23.5%), the difference was not statistically significant (p = 0.47). Conclusion This study suggested that TGC provided survivors of locally advanced or metastatic bladder cancer with encouraging antitumor activity and was generally well tolerated.