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Abstract Background To analyze the clinical manifestations, endoscopic features, pathological features, endoscopic resection, and prognosis of esophageal granular cell tumors (GCTs). Methods The present study retrospectively analyzed and followed up the clinical data of 62 patients diagnosed with esophageal GCTs who underwent endoscopic resection at Zhongshan Hospital of Fudan University between July 2007 and March 2022. The clinicopathological features, endoscopic diagnosis, and treatment experience of esophageal GCT patients were summarized. Results Among the 62 patients with esophageal GCT, there were 34 males and 28 females, with an average age of 49.3 ± 11.7 years. Only 11 patients had symptoms, such as epigastric discomfort, regurgitation or dysphagia. One patient had multiple lesions, and the rest had single lesions, totaling 63 lesions. Most lesions (53/63) were located in the median and lower esophagus, the diameters ranged from 3 to 22 mm. The endoscopic morphology of the GCTs was molar, flat, hemispherical, or irregular submucosal protuberance. Endoscopic ultrasound (EUS) was performed in 38 cases, most cases (31/38) were hypoechoic, and 32 cases were appeared as homogeneous lesions. There were no complications during or after the endoscopic operations, and the en bloc resection rate was 100%. The negative rate of microscopic incisional margin was 63.5% (40/63). No patients developed recurrence during the follow-up period. The follow-up duration was 21–197 months (100.5 months for average). Conclusion Esophageal GCT is a rare disease with no obvious symptoms and a good prognosis. Endoscopic resection is a safe and effective method of diagnosis and treatment for esophageal GCTs. A microscopic positive tumor margin may not increase the rate of recurrence.

Central Asia, a crucible of prehistoric and historical Trans-Eurasian interactions, has been pivotal in shaping cultural exchanges, population dynamics, and genetic admixture. Recent insights from ancient DNA studies have shed light on the extensive population turnover within this region, encompassing a spectrum of groups from Paleolithic hunter-gatherers to Holocene herders and the nomadic pastoralist empires of historical times. The genomic analysis of ancient pathogens across the Eurasian steppe has further deepened our understanding of pathogen origins, clonal expansions, and the intricate processes of host-pathogen coevolution in relation to varying pathogen exposures and their spread. We consolidate the latest findings pertaining to the ancient human and pathogen genomes of Central Asia, elucidating their profound influence on the genomic tapestry of contemporary Central Asians. A notable gap in the current genomic databases for Central Asia is underscored, particularly within the scope of genomics-driven precision medicine. We stress the urgent need for the development of extensive, region-specific genomic resources that hold promise for revealing the genetic blueprints underlying human traits and diseases, refining polygenic scoring models for predictive medicine, and bolstering genomic research endeavors across Central Asia.

Abstract A copper-based metal-organic framework named NH2-Cu-MOF has been synthesized and utilized as an effective broad-spectrum antimicrobial material in this article. The obtained NH2-Cu-MOF exhibits satisfying antibacterial activity against both gram-positive bacteria (S. aureus and S. epidermidis) and gram-negative bacteria (E. coli and K. peneumoniae). Additionally, the biocompatibility of this NH2-Cu-MOF has been validated through animal studies, showing no significant adverse effects, thereby confirming its high biocompatibility. These findings prove that NH2-Cu-MOF has positive effects upon the treatment of bacteria-infected wounds, which holds great potential to be applied in biochemistry field.

Abstract Background Incremental peritoneal dialysis (IPD) refers to the use of less than standard full-dose peritoneal dialysis (SPD) in end-stage renal disease patients. While the use of IPD is being reported in the literature, its safety and efficacy vs. SPD is unclear. We hereby performed a systematic review of studies comparing mortality, peritonitis, technique survival, anuria-free survival and residual renal function (RRF) between IPD and SPD. Methods All comparative studies published on PubMed, Embase, CENTRAL, Scopus, and Web of Science databases from inception to 5th September 2023 and reporting on given outcomes were eligible. Results Ten studies were included. Definitions of IPD were heterogenous and hence mostly a qualitative synthesis was undertaken. Majority of studies found no difference in patient survival between IPD and SPD. Meta-analysis of crude mortality data also presented no significant difference. Peritonitis and technique survival were also not significantly different between IPD and SPD in the majority of studies. Data on RRF was conflicting. Some studies showed that IPD was associated with the preservation of RRF while others found no such difference. Conclusion IPD may be a safe alternative to SPD in incident dialysis patients. There seems to be no difference in patient survival, peritonitis, and technique survival between the two modalities. However, the impact of IPD on RRF is still questionable. Evidence is heterogeneous and conflicting to derive firm conclusions.

Abstract Background At present, unequal allocation of medical resources represents a major problem for medical service management in China and many other countries. Equity of intensive care unit (ICU) bed allocation is essential for timely and equitable access to medical care for critically ill patients. This study analysed the equity of ICU bed allocation in 31 provincial regions in China, and the associated factors, to provide a theoretical basis for improvement in the allocation of ICU beds. Methods The equity of ICU bed allocation was investigated in 31 provincial regions in China in 2021. The Gini coefficient combined with Lorenz curves were used to analyse the current status of ICU bed allocation by both population and service area. The spatial heterogeneity and aggregation of ICU bed density were analysed using the Global Moran’s index. The spatial distribution pattern was visualized via LISA maps using the Local Moran’s index. Three grey correlation models were constructed to assess the key factors influencing ICU bed density. Finally, robustness analysis was performed to test the reliability of the results. Results The allocation of ICU beds in China was highly inequitable by service area (Gini = 0.68) and showed better balance by population distribution (Gini = 0.14). The distribution of ICU beds by service area was highly spatially clustered (Global Moran’s I = 0.22). The bed utilization rate exhibited the strongest association with ICU bed density by population. Registered nurses per 10,000 square kilometres was the strongest factor affecting ICU bed density by service area. Conclusions The allocation of ICU beds by population is better than by service area; the allocation by service area is less equitable in China. These findings emphasise the need to implement better measures to reduce ICU bed equity differences between regions and balance and coordinate medical resources. Service area size, bed utilization, the number of registered nurses and other key factors should be considered when performing regional health planning for ICU bed supply. This will increase the equitable access to critical medical services for all populations.

Abstract Exploring efficient and easily implementable prenatal screening strategies aims at birth defect prevention and control. However, there have been limited economic evaluations of non-invasive prenatal screening (NIPS) strategies in China. Furthermore, these studies were predominantly confined to local or geographically proximate provinces and lacked universality and representativeness. This study assesses the health economics of current prenatal screening strategies and NIPS as first-line screening programs, analyzing their efficacy to determine an optimal strategy. From the perspective of health economics, cost-effectiveness, cost-benefit, and single-factor sensitivity were conducted for five different screening strategies using a decision tree model. Among pregnant women aged

ObjectiveTo construct an early warning model of maintenance hemodialysis （MHD） capacity overload based upon basic dialysis data, ultrasound and routine blood biochemistry and examine its clinical effectiveness. Methods From January 2023 to December 2023, 603 patients on MHD were retrospectively reviewed. They were assigned into two sets of modeling （n = 402） and validation （n = 201） according to a ratio of 2:1. The relevant clinical were collected. And the influencing factors of MHD capacity overload in modeling set were analyzed by univariate and LASSO-Logistic regression. The risk prediction nomogram model was constructed. And consistency index, calibration curve, receiver operating characteristic （ROC） curve and decision curve were utilized for verifying the prediction model internally and externally. Results Serum albumin, Kt/V, RRF and left ventricular ejection fraction （LVEF） in overload group were lower than those in normal group. NT-proBNP, ultrasonic lung B-line and right atrial diameter were higher than those in normal group （P＜0.05）. LASSO results indicated that serum albumin, Kt/V, RRF, LVEF, NT-proBNP, ultrasonic lung B-line and right atrial internal diameter were Top 7 characteristic variables of volume overload in MHD. Logistic regression results revealed that Kt/V, serum albumin, RRF and LVEF were the protective factors for MHD volume overload. And NT-proBNP, ultrasonic lung B-line and right atrial diameter were the risk factors for MHD volume overload （P＜0.05）. The risk prediction nomogram model of capacity overload was constructed according to the influencing factors of Logistic regression. Consistency index in modeling and validation sets was 0.860 and 0.814, respectively. Calibration curve showed that the incidence of MHD capacity overload predicted by the model in modeling and validation sets was basically consistent with the actual incidence. ROC curve indicated that the area under the curve as predicted by the model in modeling and validation sets was 0.917（95%CI: 0.886-0.948） and 0.916（95%CI: 0.869-0.962）. Decision curve revealed that when the high-risk threshold of modeling set was 0-0.7 and the high risk threshold of validation set 0-0.7. The model had an excellent clinical net benefit. Conclusion In MHD patients, the occurrence of volume overload is affected by serum albumin, Kt/V, RRF, LVEF, NT-proBNP, ultrasonic lung B-line and right atrial diameter. The early warning model built according to the factors related to volume overload has excellent predictive capability and clinical benefit.

Abstract Background A comprehensive understanding of the genetic basis of rare diseases and their regulatory mechanisms is essential for human molecular genetics. However, the genetic mutant spectrum of pathogenic genes within the Chinese population remains underrepresented. Here, we reported previously unreported functional ABHD12 variants in two Chinese families and explored the correlation between genetic polymorphisms and phenotypes linked to PHARC syndrome. Methods Participants with biallelic pathogenic ABHD12 variants were recruited from the Chinese Deafness Genetics Cohort. These participants underwent whole-genome sequencing. Subsequently, a comprehensive literature review was conducted. Results Two Han Chinese families were identified, one with a compound heterozygous variant and the other with a novel homozygous variant in ABHD12. Among 65 PHARC patients, including 62 from the literature and 3 from this study, approximately 90% (57 out of 63) exhibited hearing loss, 82% (50 out of 61) had cataracts, 82% (46 out of 56) presented with retinitis pigmentosa, 79% (42 out of 53) experienced polyneuropathy, and 63% (36 out of 57) displayed ataxia. Seventeen different patterns were observed in the five main phenotypes of PHARC syndrome. A total of 33 pathogenic variants were identified in the ABHD12. Compared with other genotypes, individuals with biallelic truncating variants showed a higher incidence of polyneuropathy (p = 0.006), but no statistically significant differences were observed in the incidence of hearing loss, ataxia, retinitis pigmentosa and cataracts. Conclusions The diagnosis of PHARC syndrome is challenging because of its genetic heterogeneity. Therefore, exploring novel variants and establishing genotype-phenotype correlations can significantly enhance gene diagnosis and genetic counseling for this complex disease.

Abstract To enhance the energy efficiency and financial gains of the park integrated energy system (PIES). This paper constructs a bi-level optimization model of PIES-cloud energy storage (CES) based on source-load uncertainty. Firstly, the scheduling framework of PIES with refined power-to-gas (P2G), carbon capture and storage (CCS) and CES coupling is constructed. Moreover, a bi-level optimization model with the upper tier subject being the PIES operator and the lower tier subject being the CES operator is established under the ladder-type carbon price mechanism with reward and punishment (LCPMRP). Then a proposed entropy weight adaptive information gap decision theory method (EAIGDT) is proposed to eliminate the subjectivity factor and retain its non-probabilistic features while dealing with multiple source-load uncertainties, and according to the operator’s risk preference to build risk-averse (RA) and risk-seeking (RS) strategies, respectively. Finally, the measured data in a certain area of Xinjiang verifies the proposed optimal scheduling method. The results show that the method can effectively take into account the interests of various subjects and realise PIES low-carbon economic operation.

Abstract Studies have shown that the inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)was neuroprotective against ischemia/reperfusion(I/R) injury. Bisperoxovanadium (bpV), a derivative of vanadate, is a well-established inhibitor of PTEN. However, its function islimited due to its general inadequacy in penetrating cell membranes. Mxene(Ti3C2Tx) is a novel two-dimensional lamellar nanomaterial with an excellent ability to penetrate the cell membrane. Yet, the effects of this nanomaterial on nervous system diseases have yet to be scrutinized. Here, Mxene(Ti3C2Tx) was used for the first time to carry bpV(HOpic), creating a new nanocomposite Mxene-bpV that was probed in a cerebral I/R injury model. The findings showed that this synthetic Mxene-bpV was adequately stable and can cross the cell membraneeasily. We observed that Mxene-bpV treatment significantly increased the survival rate of oxygen glucose deprivation/reperfusion(OGD/R)--insulted neurons, reduced infarct sizes and promoted the recovery of brain function after mice cerebral I/R injury. Crucially, Mxene-bpV treatment was more therapeutically efficient than bpV(HOpic) treatment alone over the same period. Mechanistically, Mxene-bpV inhibited the enzyme activity of PTEN in vitro and in vivo. It also promoted the expression of phospho-Akt (Ser473) by repressing PTEN and then activated the Akt pathway to boost cell survival. Additionally, in PTEN transgenic mice, Mxene-bpV suppressed I/R-induced inflammatory response by promoting M2 microglial polarization through PTEN inhibition. Collectively, the nanosynthetic Mxene-bpV inhibited PTEN’ enzymatic activity by activating Akt pathway and promoting M2 microglial polarization, and finally exerted neuroprotection against cerebral I/R injury. Graphical Abstract

Abstract Background Job burnout is a prevalent and emerging challenge in the primary medical system, causing mass turnover, especially of primary medical staff. Little attention has been paid to the different dimensions of job burnout (emotional exhaustion, personality disintegration, and reduced sense of achievement), which may hinder efforts to tackle high turnover intention among primary medical staff. From the perspective of conservation of resources theory, social support and psychological capital are basic resources with potential to diminish job burnout and thus lower turnover intention. However, there is insufficient research evidence on the relationships between social support, psychological capital, and the three dimensions of job burnout within the primary medical system. Objectives Focusing on primary medical staff, this study conducts a path analysis to examine the correlations between two types of resources (social support and psychological capital) and the three dimensions of job burnout, and to test the impact of the latter on turnover intention. Based on the results, effective management strategies to improve the work stability of primary medical staff are proposed. Methods Multi-stage cluster random sampling was used to select participants in Anhui Province, China. Data were collected using a self-administered questionnaire containing measures of the main variables and demographic questions. In total, 1132 valid questionnaires were returned by primary medical staff. Structural equation modeling was used for path analysis of the data. Results Social support was negatively associated with emotional exhaustion (β = − 0.088, P = 0.020), personality disintegration (β = − 0.235, P

Abstract Background The global BOLERO-2 trial established the efficacy and safety of combination everolimus (EVE) and exemestane (EXE) in the treatment of estrogen receptor positive (ER +), HER2-, advanced breast cancer (ABC). BOLERO-5 investigated this combination in a Chinese population (NCT03312738). Methods BOLERO-5 is a randomized, double-blind, multicenter, placebo controlled, phase II trial comparing EVE (10 mg/day) or placebo (PBO) in combination with EXE (25 mg/day). The primary endpoint was progression-free survival (PFS) per investigator assessment. Secondary endpoints included PFS per blinded independent review committee (BIRC), overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), pharmacokinetics, and safety. Results A total of 159 patients were randomized to EVE + EXE (n = 80) or PBO + EXE (n = 79). By investigator assessment, treatment with EVE + EXE prolonged median PFS by 5.4 months (HR 0.52; 90% CI 0.38, 0.71), from 2.0 months (PBO + EXE; 90% CI 1.9, 3.6) to 7.4 months (EVE + EXE; 90% CI 5.5, 9.0). Similar results were observed following assessment by BIRC, with median PFS prolonged by 4.3 months. Treatment with EVE + EXE was also associated with improvements in ORR and CBR. No new safety signals were identified in BOLERO-5, with the incidence of adverse events in Chinese patients consistent with the safety profile of both drugs. Conclusion The efficacy and safety results of BOLERO-5 validate the findings from BOLERO-2, and further support the use of EVE + EXE in Chinese post-menopausal women with ER + , HER2- ABC. NCT03312738, registered 18 October 2017.

Summary: As environmental awareness grows, the agricultural sector must balance rising product demands with sustainable development. This study investigates the relationship between agricultural trade and green technological innovation, emphasizing how trade-induced efficiency improvements promote input-saving practices. Using panel data from 31 Chinese provinces between 2011 and 2021, our analysis reveals that agricultural trade significantly enhances resource use efficiency, particularly in rural areas where agriculture is concentrated. The findings provide empirical evidence of the positive effects of trade on green innovation and highlight the need for targeted policy interventions to support sustainable agricultural practices. This research underscores agricultural trade’s critical role in fostering green innovation and offers valuable insights for policymakers and agricultural businesses seeking to improve competitiveness and sustainability in an increasingly globalized economy.

ObjectivesDifferences in clinicopathological characteristics of extensive-stage small cell lung cancer (ES-SCLC) patients may influence the immune response. This study aims to evaluate the heterogeneity of response to first-line chemoimmunotherapy between subgroups in ES-SCLC to screen out suitable populations.Materials and methodsWe searched the PubMed, EMBASE, and Cochrane Library databases from inception to December 3, 2022 for randomized controlled trials (RCTs) of ES-SCLC chemoimmunotherapy. We also reviewed main conferences from January 1, 2021 to October 1, 2023. A trial-specific hazard ratio (HR) ratio for each subgroup was calculated, and these ratios were then pooled using the deft approach.ResultsA total of 9 RCTs with 4099 patients were finally included. The pooled ratios were 0.92 (95% CI = 0.77 to 1.09) for OS-HRs and 0.79 (95% CI = 0.55 to 1.13) for PFS-HRs in women versus men. The pooled ratios of OS-HRs and PFS-HRs in patients with positive versus negative PD-L1 expression were 1.26 (95% CI = 0.91 to 1.73) and 1.08 (95% CI = 0.77 to 1.52), respectively. The pooled ratios of OS-HRs and PFS-HRs in patients without versus with brain metastasis were 0.77 (95% CI = 0.59 to 1.01) and 0.71 (95% CI = 0.44 to 1.12). No statistically significant differences were also found in terms of subgroups for age, liver metastasis, smoking status, ECOG PS, LDH level, type of platinum salt and race.ConclusionWomen or patients with negative PD-L1 expression or with LDH ≤ ULN or without brain metastasis tend to benefit more from first-line chemoimmunotherapy in ES-SCLC. More trials are needed to prospectively validate the therapeutic heterogeneity among clinicopathological characteristics.Systematic review registrationhttps://inplasy.com/inplasy-2023-3-0064/ identifier, INPLASY202330064.

Abstract Alzheimer's disease (AD) is a type of dementia characterized by a decline in brain function, which leads to the inability to perform activities independently. Many researchers recognize abnormalities related to beta‐amyloid as the main cause of the disease (i.e., the beta‐amyloid hypothesis), but aging, genetics, coronary heart disease, environmental factors, gender, and other risk factors may also contribute to AD development. Three drugs with different mechanisms are available for AD treatment: cholinesterase inhibitors, N‐methyl d‐aspartate, and aducanumab. This study reviewed the therapies that are already applied in clinical practice and those that are currently being investigated for clinical use. These therapies include not only pharmacological treatments but also non‐pharmacological treatments, such as gut flora therapy and music therapy. A comprehensive understanding of these therapies is necessary to enable early intervention, improve patients' physical and mental conditions, delay the occurrence and development of AD, and extend patients' healthy lifespans.

Introduction Poststroke shoulder pain is a common complication that severely affects the recovery of upper limb motor function. Acupuncture has positive analgesic effects in treating poststroke shoulder pain, and studies have demonstrated the efficacy of transcranial direct current stimulation (tDCS) in treating patients with this pain. However, whether acupuncture combined with tDCS has a superior rehabilitation effect on poststroke shoulder pain is currently unknown. We aimed to observe the effect of the combined intervention on poststroke shoulder pain and explore its possible central analgesic mechanism.Methods and analysis This study describes a randomised controlled trial using assessor blinding. A total of 135 poststroke patients with shoulder pain will be randomly assigned in a 1:1:1 ratio to the tDCS group, acupuncture group and combined group (acupuncture plus tDCS). All three groups will undergo conventional rehabilitation treatment. Participants in the tDCS group will receive tDCS stimulation on the M1 area for 20 min, while the acupuncture group will receive 20 min of acupuncture. The combined treatment group will receive both. All treatments will be performed five times per week for 4 weeks. The primary outcome indicator in this study is the Visual Analogue Scale pain score. Secondary outcome indicators include shoulder mobility, Shoulder Pain and Disability Index, Fugl–Meyer Motor Function Scale, Modified Barthel Index Scale, Self-Rating Anxiety and Depression Scale and functional MRI. All scale results will be assessed at baseline and at 2 weeks and 4 weeks, and during follow-up at 1 month, 3 months and 6 months postdischarge. A repeated analysis of variance will be conducted to observe the group×time interaction effects of the combined intervention. Moreover, functional MRI will be applied to explore the central analgesic mechanism.Ethics and dissemination Ethics approval was obtained from the Ethics Committee of the Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine (2023KY-039–001). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences.Trial registration number ChiCTR2300078270.

Astragaloside IV(AS-IV), the main active ingredient of Astragalus, has been used as a treatment for heart failure with favorable effects, but its molecular mechanism has not been fully elucidated. Network pharmacological analysis and molecular docking revealed that Heat shock transcription factor 1 (HSF1) is a potential target of AS-IV. We designed cellular and animal experiments to investigate the role and intrinsic molecular mechanisms of AS-IV in ameliorating pressure overload-induced heart failure. In cellular experiments, Myocardial microvascular endothelial cells (MMVECs) were cultured in isolation and stimulated by adding high and low concentrations of AS-IV, and a cell model with down-regulation of HSF1 expression was constructed by using siRNA technology. Changes in the expression of key molecules of HSF1/VEGF signaling pathway and differences in tube-forming ability were detected in different groups of cells using PCR, WB and tube-forming assay. In animal experiments, TAC technology was applied to establish a pressure overload-induced heart failure model in C57 mice, postoperative mice were ingested AS-IV by gavage, and adenoviral transfection technology was applied to construct a mouse model with down-regulation of HSF1 expression.Small animal ultrasound for cardiac function assessment, MASSON staining, CD31 immunohistochemistry, and Western blotting (WB) were performed on the mice. The results showed that AS-IV could promote the expression of key molecules of HSF1/VEGF signaling pathway, enhance the tube-forming ability of MMVECs, increase the density of myocardial capillaries, reduce myocardial fibrosis, and improve the cardiac function of mice with TAC.AS-IV could modulate the HSF1/VEGF signaling pathway to promote the angiogenesis and improve the pressure overload-induced heart failure.

Objective Strengthen the legal, compliant, and rational use of medical equipment and further guide the rationalization of medical behaviors. Methods By utilizing the Internet of Things (IoT) and image analysis technology, collect real-time operation data of the equipment, establish a real-time running database for medical equipment, and cooperate with the 12 key links of the “whole life” of the equipment and the 8+6 management system framework to implement lean management of the efficiency, benefit, and effectiveness of medical equipment usage. ResultsIt realizes the improvement of the quality and efficiency of medical equipment, cost reduction and cost control, and provides data support for scientific decision-making. ConclusionThis study innovates the management model for the entire life cycle of medical equipment, providing a scientific approach to the management of hospital equipment.

Abstract Land-use change is a direct driver of biodiversity loss, projection and future land use change often consider a topical issue in response to climate change. Yet few studies have projected land-use changes over Africa, owing to large uncertainties. We project changes in land-use and land-use transfer under future climate for three specified time periods: 2021–2040, 2041–2060, and 2081–2100, and compares the performance of various scenarios using observational land-use data for the year 2020 and projected land-use under seven Shared Socioeconomic Pathways Scenarios (SSP): SSP1-1.9, SSP1-2.6, SSP2-4.5, SSP3-7.0, SSP4-3.4, SSP4-6.0 and SSP5-8.5 from 2015 to 2100 in Africa. The observational land-use types for the year 2020 depict a change and show linear relationship between observational and simulated land-use with a strong correlation of 0.89 (P

Abstract Background Methylmalonic aciduria (MMA) is a group of rare genetic metabolic disorders resulting from defects in methylmalonyl coenzyme A mutase (MCM) or intracellular cobalamin (cbl) metabolism. MMA patients show diverse clinical and genetic features across different subtypes and populations. Methods We retrospectively recruited 60 MMA patients from a single center and diagnosed them based on their clinical manifestations and biochemical assays. We then performed genetic analysis to confirm the diagnosis and identify the causal variants. Results We confirmed the common clinical manifestations of MMA reported previously. We also described four rare MMA cases with unusual symptoms or genetic variants, such as pulmonary hypertension or limb weakness in late-onset patients. We identified 15 MMACHC and 26 MMUT variants in 57 patients, including 6 novel MMUT variants. Two patients had only one MMAA variant each, and one patient had mild MMA due to mitochondrial DNA depletion syndrome caused by a SUCLA2 variant. Among 12 critically ill patients, isolated MMA was associated with higher C3, blood ammonia, and acidosis, while combined MMA was linked to hydrocephalus on skull MRI. MMACHC c.658-660delAAG and MMUT c.1280G > A variants were correlated with more severe phenotypes. Conclusions Our study demonstrates the clinical and genotypic heterogeneity of MMA patients and indicates that metabolic screening and genetic analysis are useful tools to identify rare cases.

Abstract The powerful capability of reconfigurable intelligent surfaces (RISs) in tailoring electromagnetic waves and fields has put them under the spotlight in wireless communications. However, the current designs are criticized due to their poor frequency selectivity, which hinders their applications in real-world scenarios where the spectrum is becoming increasingly congested. Here we propose a filtering RIS to feature sharp frequency-selecting and 2-bit phase-shifting properties. It permits the signals in a narrow bandwidth to transmit but rejects the out-of-band ones; meanwhile, the phase of the transmitted signals can be digitally controlled, enabling flexible manipulations of signal propagations. A prototype is designed, fabricated, and measured, and its high quality factor and phase-shifting characteristics are validated by scattering parameters and beam-steering phenomena. Further, we conduct a wireless communication experiment to illustrate the intriguing functions of the RIS. The filtering behavior enables the RIS to perform wireless signal manipulations with anti-interference ability, thus showing big potential to advance the development of next-generation wireless communications.

Introduction: Stuck tunneled central venous catheters (CVCs) have been increasingly reported. In rare cases, the impossibility of extracting the CVC from the central vein after regular traction is the result of rigid adhesions to the surrounding fibrin sheath. Forced traction during catheter removal can cause serious complications, including cardiac tamponade, hemothorax, and hemorrhagic shock. Knowledge and experience on how to properly manage the stuck catheter are still limited. Case Presentation: Here, we present two cases that highlight the successful removal of the stuck tunneled CVC via thoracotomy through the close collaboration of multidisciplinary specialists in the best possible way. Both patients underwent an unsuccessful attempt at thrombolytic therapy with urokinase, catheter traction under the guidance of digital subtraction angiography and intraluminal balloon dilation. And we reviewed the literature on stuck catheters in the hope of providing knowledge and effective approaches to attempted removal of stuck catheters. Conclusion: There is no standardized procedure for dealing with stuck catheters. Intraluminal percutaneous transluminal angioplasty should be considered as the first-line treatment, while open surgery represents a second option only in the event of failure. Care must be taken that forced extubation can cause patients life-threatening.

Abstract A transition away from coal power always maintains a high level of complexity as there are several overlapping considerations such as technical feasibility, economic costs, and environmental and health impacts. Here, we explore the cost-effectiveness uncertainty brought by policy implementation disturbances of different coal power phaseout and new-built strategies (i.e., the disruption of phaseout priority) in China based on a developed unit-level uncertainty assessment framework. We reveal the opportunity and risk of coal transition decisions by employing preference analysis. We find that, the uncertainty of a policy implementation might lead to potential delays in yielding the initial positive annual net benefits. For example, a delay of six years might occur when implementing the prior phaseout practice. A certain level of risk remains in the implementation of the phaseout policy, as not all strategies can guarantee the cumulative positive net benefits from 2018–2060. Since the unit-level heterogeneities shape diverse orientation of the phaseout, the decision-making preferences would remarkably alter the selection of a coal power transition strategy. More strikingly, the cost-effectiveness uncertainty might lead to missed opportunities in identifying an optimal strategy. Our results highlight the importance of minimizing the policy implementation disturbance, which helps mitigate the risk of negative benefits and strengthen the practicality of phaseout decisions.

Abstract In the era of 5G, billions of terminal devices achieve global interconnection and intercommunication, which leads to the generation of massive data. However, the existing cloud‐based data‐sharing mechanism faces challenges such as sensitive information leakage and data islands, which makes it difficult to achieve secure sharing across domains. In this paper, the authors propose a fine‐grained data‐sharing scheme based on blockchain and ciphertext policy attribute‐based encryption, and design a verifiable outsourced computation method to reduce the computational pressure of end users. Second, the authors comprehensively consider the user's identity privacy and transaction privacy, and propose a multi‐level privacy protection method based on ring signature and garbled bloom filter, which enhance the user's data privacy and availability, and prevent the traceability of requests. Finally, the authors design a set of interconnected smart contracts, and verify that their scheme can achieve secure and efficient data sharing through security analysis and performance testing.

Pidan is an original traditional food in China, which has attracted extensive attention of researchers because of its unique color, fragrance, taste and functions of clearing heat, purging fire, reducing inflammation. Metallic compounds, alkali concentration, and temperature are important in the process of gel formation. Although many studies related to Pidan have been published, there is no systematic summary on the formation mechanism of gel and flavor profile. In this paper, the regulation mechanism of metal compounds in alkaline solutions, and the formation mechanism of gel, color, flavor profile, and Songhua are systematically and comprehensively reviewed to provide theoretical support for the production development and processing of Pidan.

BackgroundBoth inflammatory cytokines and the gut microbiome are susceptibility factors for vascular dementia (VaD). The trends in the overall changes in the dynamics of inflammatory cytokines and in the composition of the gut microbiome are influenced by a variety of factors, making it difficult to fully explain the different effects of both on the different subtypes of VaD. Therefore, this Mendelian randomization (MR) study identified the inflammatory cytokines and gut microbiome members that influence the risk of developing VaD and their causal effects, and investigated whether inflammatory cytokines are gut microbiome mediators affecting VaD.MethodsWe obtained pooled genome-wide association study (GWAS) data for 196 gut microbiota and 41 inflammatory cytokines and used GWAS data for six VaD subtypes, namely, VaD (mixed), VaD (multiple infarctions), VaD (other), VaD (subcortical), VaD (sudden onset), and VaD (undefined). We used the inverse-variance weighted (IVW) method as the primary MR analysis method. We conducted sensitivity analyses and reverse MR analyses to examine reverse causal associations, enhancing the reliability and stability of the conclusions. Finally, we used multivariable MR (MVMR) analysis to assess the direct causal effects of inflammatory cytokines and the gut microbiome on the risk of VaD, and performed mediation MR analysis to explore whether inflammatory factors were potential mediators.ResultsOur two-sample MR study revealed relationships between the risk of six VaD subtypes and inflammatory cytokines and the gut microbiota: 7 inflammatory cytokines and 14 gut microbiota constituents were positively correlated with increased VaD subtype risk, while 2 inflammatory cytokines and 11 gut microbiota constituents were negatively correlated with decreased VaD subtype risk. After Bonferroni correction, interleukin-18 was correlated with an increased risk of VaD (multiple infarctions); macrophage migration inhibitory factor was correlated with an increased risk of VaD (sudden onset); interleukin-4 was correlated with a decreased risk of VaD (other); Ruminiclostridium 6 and Bacillales were positively and negatively correlated with the risk of VaD (undefined), respectively; Negativicutes and Selenomonadales were correlated with a decreased risk of VaD (mixed); and Melainabacteria was correlated with an increased risk of VaD (multiple infarctions). Sensitivity analyses revealed no multilevel effects or heterogeneity and no inverse causality between VaD and inflammatory cytokines or the gut microbiota. The MVMR results further confirmed that the causal effects of Negativicutes, Selenomonadales, and Melainabacteria on VaD remain significant. Mediation MR analysis showed that inflammatory cytokines were not potential mediators.ConclusionThis study helps us to better understand the pathological mechanisms of VaD and suggests the potential value of targeting increases or decreases in inflammatory cytokines and gut microbiome members for VaD prevention and intervention.

Background Children and adolescents who are overweight and obese represent a growing public health issue. The use of step-monitoring devices as an intervention tool may be a simple, cost-effective, and easily replicable solution for addressing obesity in children and adolescents. No prior systematic reviews have evaluated the effectiveness of utilizing step-monitoring devices as an intervention method for obesity in children and adolescents. Methods Previous studies on using step-monitoring devices to prevent and treat obesity in children and adolescents were identified in the following databases: Web of Science, EMBASE, PubMed, Cochrane Library, SPORTDiscus, and SCOPUS. The search period for each database ranged from the year of their inception to 8 March 2023 (updated in June 2024). Meta-analyses were performed for mean differences (MDs) in body mass index (BMI), BMI z -score (BMI-Z), body fat, waist circumference, and body weight. Results From 12,907 relevant records, 23 studies were included in this meta-analysis. The included studies were mainly at low risk of bias, except for blinding. Step-monitoring device-based interventions had significant effects in reducing BMI-Z (MD −0.06; 95% CI −0.10 to −0.02), body fat (MD −0.95%; 95% CI −1.35 to −0.54), and body weight (MD −1.23 kg; 95% CI −2.36 to −0.10). However, there was no significant effect on BMI (MD −0.16 kg/m 2 ; 95% CI −0.55 to 0.22) and waist circumference (MD −0.33 cm; 95% CI −1.23 to 0.58). Subgroup analyses indicated that participants who were overweight or obese showed greater intervention effects on BMI and BMI-Z compared to participants with normal weight. The programs with an intervention duration of ≤6 months presented a greater intervention effect on BMI-Z than those with an intervention duration of more than 6 months. The programs that established goals had a greater intervention effect on body fat than those that did not. Conclusions Step-monitoring devices may be an effective and generalizable intervention tool for the prevention and treatment of obesity in children and adolescents. Future studies should further explore how to set step goals and the duration of interventions to achieve better intervention effects.

IntroductionThe optimal dosage of recombinant human luteinizing hormone (r-hLH) and its impact on endometrial thickness (EMT) when administered alongside recombinant human follicle-stimulating hormone (r-hFSH) during controlled ovarian stimulation (COS) for in vitro fertilization/intracytoplasmic sperm injection and embryo transfer are uncertain, which formed the aims of this systematic review and meta-analysis.MethodA search was performed in PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, and Wanfang from its inception to 10 July 2023. Twenty-seven Randomized controlled trials comparing r-hFSH/r-hLH co-treatment with r-hFSH alone during in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) were included. Pooled odds ratios (OR) for dichotomous data and mean differences (MD) for continuous data, with their respective 95% confidence intervals (CI), were generated. Meta-analysis employed fixed-effect or random-effect models based on heterogeneity, using Q-test and I2-index calculations. The main outcomes included EMT on trigger day, clinical pregnancy rate (CPR) and live birth rate (LBR).Resultsr-hFSH/r-hLH significantly increased EMT on trigger day (MD = 0.27; 95% CI, 0.11–0.42; I2 = 13%), but reduced oocyte number (MD = −0.60; 95% CI, −1.07 to −0.14; I2 = 72%) and high-quality embryos (MD = −0.76; 95% CI, −1.41 to −0.10; I2 = 94%) than r-hFSH alone, more pronounced with the gonadotrophin-releasing hormone agonist long protocol. A subgroup analysis showed r-hLH at 75 IU/day increased CPR (OR = 1.23; 95% CI, 1.02–1.49; I2 = 16%) and EMT on trigger day (MD = 0.40; 95% CI, 0.19–0.61; I2 = 0%). Participants ≥35 years of age exhibited decreased retrieved oocytes (MD = −1.26; 95% CI, −1.78 to −0.74; I2 = 29%), but an increase in EMT on trigger day (MD = 0.26; 95% CI, 0.11–0.42; I2 = 29%).Conclusionr-hFSH/r-hLH during COS significantly improved EMT compared to r-hFSH alone. An r-hLH dose of 75 IU/day may be considered for optimal pregnancy outcomes, which still require further clinical studies to support this dosing regime.Systematic Review Registration[www.crd.york.ac.uk/PROSPERO], identifier [CRD42023454584].

BackgroundDonepezil in combination with memantine is a widely used clinical therapy for moderate to severe dementia. However, real-world population data on the long-term safety of donepezil in combination with memantine are incomplete and variable. Therefore, the aim of this study was to analyze the adverse events (AEs) of donepezil in combination with memantine according to US Food and Drug Administration Adverse Event Reporting System (FAERS) data to provide evidence for the safety monitoring of this therapy.MethodsWe retrospectively analyzed reports of AEs associated with the combination of donepezil and memantine from 2004 to 2023 extracted from the FAERS database. Whether there was a significant association between donepezil and memantine combination therapy and AEs was assessed using four disproportionality analysis methods, namely, the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. To further investigate potential safety issues, we also analyzed differences and similarities in the time of onset and incidence of AEs stratified by sex and differences and similarities in the incidence of AEs stratified by age.ResultsOf the 2,400 adverse drug reaction (ADR) reports in which the combination of donepezil and memantine was the primary suspected drug, most of the affected patients were female (54.96%) and older than 65 years of age (79.08%). We identified 22 different system organ classes covering 100 AEs, including some common AEs such as dizziness and electrocardiogram PR prolongation; fall, pleurothotonus and myoclonus were AEs that were not listed on the drug label. Moreover, we obtained 88 reports of AEs in men and 100 reports of AEs in women; somnolence was a common AE in both men and women and was more common in women, whereas pleurothotonus was a more common AE in men. In addition, we analyzed 12 AEs in patients younger than 18 years, 16 in patients between 18 and 65 years, and 113 in patients older than 65 years. The three age groups had distinctive AEs, but lethargy was the common AE among all age groups. Finally, the median time to AE onset was 19 days in all cases. In both men and women, most AEs occurred within a month of starting donepezil plus memantine, but some continued after a year of treatment.ConclusionOur study identified potential and new AEs of donepezil in combination with memantine; some of these AEs were the same as in the specification, and some of the AE signals were not shown in the specification. In addition, there were sex and age differences in some of the AEs. Therefore, our findings may provide valuable insights for further studies on the safety of donepezil and memantine combination therapy, which are expected to contribute to the safe use of this therapy in clinical practice.

IntroductionWaardenburg syndrome (WS) is a genetic disorder characterized by hearing loss, hypopigmentation, and distinct facial features. Despite > 60% molecular diagnosis rate for WS patients, pathogenic variants within coding regions are predominant, with few non-coding copy number variations (CNVs) reported.MethodsIn this study, we performed whole genome sequencing (WGS) on 59 undiagnosed WS patients and analyzed the CNVs within the promoter and enhancer regions of the SOX10 gene.ResultsWe identified five novel pathogenic deletions ranging from 448 bp to 70 kb upstream of SOX10. Two deletions were in the enhancer region, while three were in the promoter and 5'UTR region. These CNVs manifested as WS type II in eight patients from five unrelated families, demonstrating phenotypic heterogeneity. Furthermore, analysis of CNV1 within the enhancer region suggested a potential mechanism involving Alu-mediated non-allelic homologous recombination (NAHR).ConclusionOur findings extend the mutation spectrum of the SOX10 gene and elucidate the pathogenic role of CNVs in cis-regulatory elements, particularly variations in enhancer and promoter regions, thereby enhancing clinical gene detection and interpretation of non-coding regions.

Tunable Airy beams with controllable propagation trajectories have sparked interest in various fields, such as optical manipulation and laser fabrication. Existing research approaches encounter challenges related to insufficient compactness and integration feasibility, or they require enhanced tunability to enable real-time dynamic manipulation of the propagation trajectory. In this work, we present a novel method that utilizes a dual metasurface system to surpass these limitations, significantly enhancing the practical potential of the Airy beam. Our approach involves encoding a cubic phase profile and two off-axis Fresnel lens phase profiles across the two metasurfaces. The validity of the proposed strategy has been confirmed through simulation and experimental results. The proposed meta-device addresses the existing limitations and lays the foundation for broadening the applicability of Airy beams across diverse domains, encompassing light-sheet microscopy, laser fabrication, optical tweezers, etc.

Abstract Background The implementation of a care bundle might improve functional outcome for patients with intracerebral hemorrhage (ICH). However, the impact of anti-hypertensive treatment on ICH outcomes remains uncertain. Our objective is to examine whether early blood pressure (BP) lowering therapy within first 12 h is associated with good outcome in ICH patients. Methods We included acute ICH patients who had baseline computed tomography (CT) scans within 6 h after onset of symptoms between October 2013 and December 2021. Early BP reduction was defined as use of anti-hypertensive agents within 12 h after onset of symptom. The clinical characteristics were compared between patients who received early BP lowering therapy and those without. The associations between early BP lowering and good outcome and functional independence at 3 months were assessed by using multivariable logistic regression analyses. Results A total of 377 patients were finally included in this study for outcome analysis. Of those, 212 patients received early BP reduction within 12 h after ICH. A total of 251 (66.6%) patients had good outcome. After adjustment for age, admission systolic BP, admission GCS score, baseline hematoma volume, hematoma expansion, and presence of intraventricular hemorrhage, early BP lowering therapy was associated with functional independence (adjusted odd ratio:1.72, 95% confidence interval:1.03–2.87; P = 0.039) and good outcome (adjusted odd ratio: 2.02, 95% confidence interval:1.08–3.76; P = 0.027). Conclusions In ICH patients presenting within 6 h after symptom onset, early BP reduction within first 12 h is associated with good outcome and functional independence when compared to those who do not undergo such early intervention. Implementation of quality measures to ensure early BP reduction is crucial for management of ICH.

Abstract Background Missing data is frequently an inevitable issue in cohort studies and it can adversely affect the study's findings. We assess the effectiveness of eight frequently utilized statistical and machine learning (ML) imputation methods for dealing with missing data in predictive modelling of cohort study datasets. This evaluation is based on real data and predictive models for cardiovascular disease (CVD) risk. Methods The data is from a real-world cohort study in Xinjiang, China. It includes personal information, physical examination data, questionnaires, and laboratory biochemical results from 10,164 subjects with a total of 37 variables. Simple imputation (Simple), regression imputation (Regression), expectation-maximization(EM), multiple imputation (MICE) , K nearest neighbor classification (KNN), clustering imputation (Cluster), random forest (RF), and decision tree (Cart) were the chosen imputation methods. Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) are utilised to assess the performance of different methods for missing data imputation at a missing rate of 20%. The datasets processed with different missing data imputation methods were employed to construct a CVD risk prediction model utilizing the support vector machine (SVM). The predictive performance was then compared using the area under the curve (AUC). Results The most effective imputation results were attained by KNN (MAE: 0.2032, RMSE: 0.7438, AUC: 0.730, CI: 0.719-0.741) and RF (MAE: 0.3944, RMSE: 1.4866, AUC: 0.777, CI: 0.769-0.785). The subsequent best performances were achieved by EM, Cart, and MICE, while Simple, Regression, and Cluster attained the worst performances. The CVD risk prediction model was constructed using the complete data (AUC:0.804, CI:0.796-0.812) in comparison with all other models with p

Abstract Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status.

Abstract Background Pathogenic (P) copy number variants (CNVs) may be associated with second-trimester ultrasound soft markers (USMs), and noninvasive prenatal screening (NIPS) can enable interrogate the entire fetal genome to screening of fetal CNVs. This study evaluated the clinical application of NIPS for detecting CNVs among fetuses with USMs in pregnant women not of advanced maternal age (AMA). Results Fetal aneuploidies and CNVs were identified in 6647 pregnant women using the Berry Genomics NIPS algorithm.Those with positive NIPS results underwent amniocentesis for prenatal diagnosis. The NIPS and prenatal diagnosis results were analyzed and compared among different USMs. A total of 96 pregnancies were scored positive for fetal chromosome anomalies, comprising 37 aneuploidies and 59 CNVs. Positive predictive values (PPVs) for trisomy 21, trisomy 18, trisomy 13, and sex chromosome aneuploidies were 66.67%, 80.00%, 0%, and 30.43%, respectively. NIPS sensitivity for aneuploidies was 100%. For CNVs, the PPVs were calculated as 35.59% and false positive rate of 0.57%. There were six P CNVs, two successfully identified by NIPS and four missed, of which three were below the NIPS resolution limit and one false negative. The incidence of aneuploidies was significantly higher in fetuses with absent or hypoplastic nasal bone, while that of P CNVs was significantly higher in fetuses with aberrant right subclavian artery (ARSA), compared with other groups. Conclusions NIPS yielded a moderate PPV for CNVs in non-AMA pregnant women with fetal USM. However, NIPS showed limited ability in identifying P CNVs. Positive NIPS results for CNVs emphasize the need for further prenatal diagnosis. We do not recommend the use of NIPS for CNVs screening in non-AMA pregnant women with fetal USM, especially in fetuses with ARSA.

Abstract Objective To assess the prevalence and factors associated with early cognitive impairment in intracerebral hemorrhage (ICH) patients and to describe short‐term recovery trajectories among ICH patients with early cognitive impairment. Methods We prospectively enrolled ICH patients without baseline dementia in our institutions. Cognitive function was assessed using mini‐mental state examination (MMSE), and functional outcome was evaluated at discharge, 3, and 6 months after symptoms onset using the modified Rankin Scale (mRS). We used multinomial logistic regression models to investigate potential risk factors and generalized linear models to analyze the functional outcome data. Results Out of 181 patients with ICH, 167 were included in the final analysis. Early cognitive impairment occurred in 60.48% of patients with ICH. Age (odds ratio [OR] per 1‐year increase, 1.037; 95% confidence interval [CI], 1.003–1.071; p = 0.034), National Institutes of Health Stroke Scale (NIHSS) score (OR per 1‐point increase, 1.146; 95% CI, 1.065–1.233; p

Objective: To assess the safety and feasibility of ultra-remote robot-assisted laparoscopic hysterectomy using the Edge Multi-Port Endoscopic Surgical Robot MP1000 (Shenzhen Edge Medical Co., Ltd., Shenzhen, China) combined with 5G communication technology. Methods: A case of remote robot-assisted laparoscopic hysterectomy was successfully completed on May 2024 by using the Edge Multi-Port Endoscopic Surgical Robot MP1000 at Zhongnan Hospital of Wuhan University and the People's Liberation Army General Hospital, approximately 1, 200 ​km apart. The procedure was simultaneously broadcast during the 36th Annual Meeting of the International Society for Gynecologic Endoscopy in Conjuction with the Peking University Gynecologic Oncology Summit Forum. Results: A 49-year-old female was hospitalized in the Department of Gynecology of Zhongnan Hospital of Wuhan University for frequent urination for half a year and increased menstrual flow for over a month. The patient was diagnosed with abnormal uterine bleeding caused by multiple uterine leiomyoma and endometrial polyps, combined with moderate anemia. There were no contraindications for surgery, and the patient had surgical indications. On May 2024, the patient underwent a 5G remote robot-assisted laparoscopic hysterectomy and bilateral salpingectomy under general anesthesia. The procedure was successful, with no surgical complications and no interruptions during the live broadcast. The intraoperative blood loss was approximately 20 ​mL, and the surgery lasted about 70 ​min. The bidirectional latency during the operation was around 19 ​ms, with no adverse events related to the robot or the network. The patient recovered well postoperatively and was discharged on the fourth day with no postoperative complications. Conclusion: Preliminary findings indicate that ultra-remote robot-assisted laparoscopic hysterectomy is safe and feasible with the support of 5G communication technology. This surgery represents the first globally broadcast remote procedure in the field of gynecology, marking a new milestone in the stability and safety of China's remote medical technology. Remote robotic surgery is expected to be widely promoted in the future, providing services to patients in areas with limited medical resources.

Abstract Objective To evaluate the efficacy and safety of peribulbar triamcinolone acetonide injection for treating ocular myasthenia gravis (OMG), with a comparison of traditional oral drug therapy. Methods A total of 22 patients with OMG who received periocular triamcinolone acetonide injection (initially 20 mg weekly, then once per month later if symptoms were improved) from July 2019 to July 2022 were evaluated by a comparison of symptom degree before and after treatment. Adverse reactions were also monitored during the period of treatment. The period of follow-up was more than 6 months. Additionally, a comparison of the treatment efficacy between this periocular injection and traditional oral administration was performed in OMG patients. Results After 4 weeks of treatment, the degree of ptosis in OMG patients decreased to -3.00 ± 0.69, compared to the value (-0.86 ± 1.32) before treatment. The degree of ophthalmoplegia also decreased from 3.12 ± 0.72 to 0.86 ± 0.88 (P

Abstract Background The American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) guidelines recommend using variant enrichment among cases as "strong" evidence for pathogenicity per the PS4 criterion. However, quantitative support for PS4 thresholds from real-world Mendelian case–control cohorts is lacking. Methods To address this gap, we evaluated and established PS4 thresholds using data from the Chinese Deafness Genetics Consortium. A total of 9,050 variants from 13,845 patients with hearing loss (HL) and 6,570 ancestry-matched controls were analyzed. Positive likelihood ratio and local positive likelihood ratio values were calculated to determine the thresholds corresponding to each strength of evidence across three variant subsets. Results In subset 1, consisting of variants present in both cases and controls with an allele frequency (AF) in cases ≥ 0.0005, an odds ratio (OR) ≥ 6 achieved strong evidence, while OR ≥ 3 represented moderate evidence. For subset 2, which encompassed variants present in both cases and controls with a case AF 2.27 or allele count ≥ 3) and the PS4_Moderate threshold (allele count ≥ 6), respectively. Reanalysis applying the adjusted PS4 criteria changed the classification of 15 variants and enabled diagnosis of an additional four patients. Conclusions Our study quantified evidence strength thresholds for variant enrichment in genetic HL cases, highlighting the importance of defining disease/gene-specific thresholds to improve the precision and accuracy of clinical genetic testing.

BackgroundCurrent evidences suggest that Proprotein Convertase Subtilisin/kexin Type 9 inhibitors (PCSK9i) exhibit a protective influence on acute coronary syndrome (ACS). Nevertheless, further investigation is required to comprehend the impact and mechanisms of these pharmaceutical agents on inflammatory factors and arterial stiffness (AS) in patients with ACS. Consequently, the objective of this study is to ascertain the influence of PCSK9i on arterial stiffness in ACS patients and elucidate the underlying mechanisms behind their actions.MethodsThis study employed Mendelian randomization (MR) analysis to examine the association between genetic prediction of PCSK9 inhibition and arterial stiffness. Data of 71 patients with ACS were retrospectively collected, including PCSK9i group (n = 36, PCSK9 inhibitors combined with statins) and control group (n = 35, statins only). Blood lipid levels, inflammatory markers and pulse wave velocity (PWV) data were collected before treatment and at 1 and 6 months after treatment for analysis. Additionally, cell experiments were conducted to investigate the impact of PCSK9i on osteogenesis of vascular smooth muscle cells (VSMCs), utilizing western blot (WB), enzyme-linked immunosorbent assay (ELISA), and calcification index measurements.ResultsThe results of the MR analysis suggest that genetic prediction of PCSK9 inhibition has potential to reduce the PWV. Following treatment of statins combined with PCSK9 inhibitors for 1 and 6 months, the PCSK9i group exhibited significantly lower levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen (FIB) and procalcitonin (PCT) compared to the control group (p

IntroductionMicroRNA-875-5p (miR-875-5p) is a cancer-related microRNA. It has been demonstrated that miR−875−5p participates in the development of various types of cancer such as hepatocellular carcinoma, gastric carcinoma, prostate and bladder cancer. Previous research suggested that miR-875 is implicated in the development of cervical cancer cells. However, the exact role and function of miR−875−5p in cervical cancer remain unexplored. It is important to examine the role and function of miR-875-5p and the associated signaling pathway, as the findings may have diagnostic and therapeutic significance. Thus, in this study, we investigated the effect of miR-875-5p on the growth and metastasis of cervical cancer cells and the possible underlying mechanisms.MethodsReverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-875-5p in cervical cancer cells and normal cervical epithelium. After overexpression or co-expression of miR-875-5p in cells, the changes in cell function were analyzed. Western blot was used to detect the expression changes of epithelial-mesenchymal transition (EMT) -related proteins and autophagy-related proteins.ResultsFunctional studies demonstrated that miR-875-5p overexpression significantly inhibited the proliferation, migration, invasion, and EMT, and promotes apoptosis and autophagy of cervical cancer cells., while miR-875-5p knockdown promoted the proliferation, migration, invasion, and EMT, and inhibited apoptosis and autophagy cervical cancer cells. Furthermore, Western blot results showed that overexpression of miR-875-5p downregulated the expressions of N-cadherin, Snail, Vimentin and microtubule-associated protein 1 light chain 3B I (LC3B I). Conversely, miR-875-5p upregulated the expression of E-cadherin.ConclusionIn conclusion, our findings suggest that miR-875-5p functions as a tumor inhibitor suppressing the growth and metastasis of cervical cancer. Overexpression of miR-875-5p inhibits malignant behavior and promotes autophagy and apoptosis in cervical cancer cells. These findings advance our understanding of the role and function of miR-875-5p in cervical cancer and could facilitate the development of early genetic markers or biomarkers and therapeutic targets for cervical cancer.

ObjectiveTo systematically evaluate the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) on language function in patients with non-fluent aphasia post-stroke.MethodsWe selected randomized clinical trials (RCT) that involved stroke patients with non-fluent aphasia, whose intervention was rTMS vs. no therapy or other therapy. Two researchers autonomously reviewed the literature based on the specified criteria for inclusion and exclusion and completed the process of data extraction, data verification, and quality evaluation. Meta-analysis was performed using RevMan 5.41 and Stata MP 172, while the assessment of risk of bias was carried out utilizing the Risk of Bias version 2 tool (RoB2)3.ResultsThe meta-analysis involved 47 RCTs, encompassing 2,190 patients overall. The indexes indicated that rTMS has the potential to decrease the severity of non-fluent aphasia in stroke patients, including improvement of the capability of repetition, naming, and spontaneous language. The determination of BDNF in the serum of patients was also increased. In addition, rTMS reduced the likelihood of depression in stroke patients.ConclusionTo summarize the relevant studies, rTMS has significant effects on improving the language abilities of stroke patients suffering from non-fluent aphasia, including the abilities of repetition, naming, and spontaneous language.

China is now confronting the intertwined challenges of air pollution and climate change. Given the high synergies between air pollution abatement and climate change mitigation, the Chinese government is actively promoting synergetic control of these two issues. The Synergetic Roadmap project was launched in 2021 to track and analyze the progress of synergetic control in China by developing and monitoring key indicators. The Synergetic Roadmap 2022 report is the first annual update, featuring 20 indicators across five aspects: synergetic governance system and practices, progress in structural transition, air pollution and associated weather-climate interactions, sources, sinks, and mitigation pathway of atmospheric composition, and health impacts and benefits of coordinated control. Compared to the comprehensive review presented in the 2021 report, the Synergetic Roadmap 2022 report places particular emphasis on progress in 2021 with highlights on actions in key sectors and the relevant milestones. These milestones include the proportion of non-fossil power generation capacity surpassing coal-fired capacity for the first time, a decline in the production of crude steel and cement after years of growth, and the surging penetration of electric vehicles. Additionally, in 2022, China issued the first national policy that synergizes abatements of pollution and carbon emissions, marking a new era for China's pollution-carbon co-control. These changes highlight China's efforts to reshape its energy, economic, and transportation structures to meet the demand for synergetic control and sustainable development. Consequently, the country has witnessed a slowdown in carbon emission growth, improved air quality, and increased health benefits in recent years.

Objective: The regional inequality of emergency medicine beds distribution has a great impact on population health as well as the accessibility of emergency services. This study aimed to explore the regional inequality of emergency medicine bed distribution and its influencing factors.Methods: The Gini coefficient and health resource agglomeration were used to analyze the regional inequality of emergency medicine beds distribution by area from 2012 to 2021 in China. Grey correlation models were used to explore the factors influencing the regional inequality of emergency medicine beds distribution.Results: From 2012 to 2021, Gini coefficients of emergency medicine beds distribution by geographic in China showed a worsening trend, rising from 0.6229 to 0.6636. The average HRAD index was 3.43 in the east and 0.44 in the west. Population structure factors have the greatest influence on the regional inequality of emergency medicine beds distribution.Conclusion: Health resources allocation strategy only according to population size should be changed. In formulating policies for emergency medicine beds allocation should take into account population structure, financial structure of expenditure, the inequality of geographical distribution and so on.

Abstract Structural repair of the intestinal epithelium is strongly correlated with disease remission in inflammatory bowel disease (IBD); however, ulcer healing is not addressed by existing therapies. To address this need, this study reports the use of a small molecule prolyl hydroxylase (PHD) inhibitor (DPCA) to upregulate hypoxia‐inducible factor one‐alpha (HIF‐1α) and induce mammalian regeneration. Sustained delivery of DPCA is achieved through subcutaneous injections of a supramolecular hydrogel, formed through the self‐assembly of PEG‐DPCA conjugates. Pre‐treatment of mice with PEG‐DPCA is shown to protect mice from epithelial erosion and symptoms of dextran sodium sulfate (DSS)‐induced colitis. Surprisingly, a single subcutaneous dose of PEG‐DPCA, administered after disease onset, leads to accelerated weight gain and complete restoration of healthy tissue architecture in colitic mice. Rapid DPCA‐induced restoration of the intestinal barrier is likely orchestrated by increased expression of HIF‐1α and associated targets leading to an epithelial‐to‐mesenchymal transition. Further investigation of DPCA as a potential adjunctive or stand‐alone restorative treatment to combat active IBD is warranted.

Respiratory system diseases caused by respiratory viruses are common and exert tremendous pressure on global healthcare system. In our previous studies, we found that Long non-coding RNA NRAV (Lnc NRAV) and its target molecule Rab5c plays a significant role in respiratory virus infection. However, the mechanism by which Rab5c affects virus replication remains unclear. Rab5c, a protein mainly localized on the cell membranes and in early endosomes and phagosomes, participates in endocytosis mediated by clathrin and regulates the fusion of early endosome, maturation of early phagosomes, and autophagy. Therefore, we inferred that Rab5c impacts virus replication, which might be related to endocytosis or autophagy. We selected RSV (respiratory syncytial virus) as a representative enveloped virus and ADV (Adenovirus) as a representative non-enveloped virus to explore the possible mechanism of RSV and ADV replication promoted by Rab5c in A549 cells and in Rab5c-overexpressing mice. Here, we confirmed that the activated Rab5c promotes RSV and ADV replication and the inactivated Rab5c inhibits their replication. However, Rab5c promoting RSV and ADV replication is not mediated by endocytosis rather by autophagy in respiratory epithelial cells. Our study showed that Rab5c upregulates LC3-Ⅱ (microtubule-associated protein 1 light chain 3 beta) protein expression levels by interacting with Beclin1, a key autophagy molecule, which can induce autophagy and promote replication of ADV and RSV. This study enriches the understanding of the interaction between respiratory viruses and Rab5c, providing new insights for virus prevention and treatment.

Abstract The toughest‐ever clean air actions to date in China have helped to reduce national air pollutant emissions significantly in recent years. However, the heterogeneous mitigation paths and their determinated factors among regions were less concerned. To direct regional mitigation strategies more efficiently, we compiled a time‐series emission inventory of Chinese 30 provinces for SO2, NOx, primary PM2.5 and CO2 at detailed socioeconomic sectors, and then used spatial‐temporal index decomposition analysis to evaluate the driving forces for changes in regional pollutant emissions and emission intensities from 2012 to 2017 and from 2017 to 2020, separately. Our results showed that end‐of‐pipe control measures dominated the decreasing trend of China's pollutant emissions (38%–68% for SO2, NOx, and primary PM2.5), but their relative dominance diminished gradually, and the effects from energy policy emerged, even outweighing the former in southern areas during the second phase. Though driven by different factors, the chemistry, nonmetal, metal, energy and residential sectors dominated regional reduction trend and with varying degrees. Clean air action led to the convergence of regional emission intensity, while optimizing and upgrading industrial structure and improving energy efficiency is still necessary for further reduction in northern and western areas at present.

Diabetic retinopathy is an ocular disease caused by long-term damage to the retina due to high blood sugar levels. Elevated blood sugar can impair the microvasculature in the retina, leading to vascular abnormalities and the formation of abnormal new blood vessels. These changes can manifest in the retina as hemorrhages, leaks, vessel dilation, retinal edema, and retinal detachment. The retinas of individuals with diabetes exhibit different morphologies compared to those without the condition. Most histological images cannot be accurately described using traditional geometric shapes or methods. Therefore, this study aims to evaluate and classify the morphology of retinas with varying degrees of severity using multifractal geometry. In the initial experiments, two-dimensional empirical mode decomposition was employed to extract high-frequency detailed features, and the classification process was based on the most relevant features in the multifractal spectrum associated with disease factors. To eliminate less significant features, the random forest algorithm was utilized. The proposed method achieved an accuracy of 96%, sensitivity of 96%, and specificity of 95%.

Abstract Background Concentrated growth factor (CGF), a new autologous platelet concentrate, has been widely investigated to the adjunctive treatment of oral diseases. This study aims to evaluate the efficacy of CGF in the surgical treatment of oral diseases. Methods MEDLINE, Web of Science, Scopus, Cochrane, and EMBASE databases were searched up to July 2023. Only randomized clinical trials were included. The methodologic quality was evaluated by the Cochrane Risk of Bias Tool. RevMan 5.4 software was used for data analysis. Results In the treatment of periodontal intrabony defects, bone graft combined with CGF was significantly superior to bone graft (P

The development of urban underground space (UUS) is of great significance for sustainable urban development because it has potential to solve many urban problems. However, the development of UUS is limited because there are still a lot of constraints and challenges. To better understand the constraining factors of developing UUS and improve the development and utilization of UUS, this study conducts a comprehensive survey of existing literature retrieved from the Web of Science Core Collection database. Five main constraining factors, including the limited geological conditions, high cost, lack of natural light and ventilation, high incidence, and difficulty in collecting data and information on UUS, have been discussed to better understand how they affect the development of UUS. Based on the survey, the critical success factors of developing UUS, such as the effective governance structure, planning system for integrating UUS into urban development, coordination of the design of ground and underground, delineation of land property rights of UUS, and application of information techniques in the use of UUS, have been identified and discussed. In addition, knowledge gaps in the studies on development of UUS have been identified. Finally, the research trends and future directions have been proposed for better understanding and practice of UUS development.