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The increasing frequency of cervical and lumbar spine disorders, driven by aging and evolving lifestyles, has led to a rise in spinal surgeries using pedicle screws. Robotic spinal surgery systems have emerged as a promising innovation, offering enhanced accuracy in screw placement and improved surgical outcomes. We focused on literature of this field from the past 5 years, and a comprehensive literature search was performed using PubMed and Google Scholar. Robotic spinal surgery systems have significantly impacted spinal procedures by improving pedicle screw placement accuracy and supporting various techniques. These systems facilitate personalized, minimally invasive, and low‐radiation interventions, leading to greater precision, reduced patient risk, and decreased radiation exposure. Despite advantages, challenges such as high costs and a steep learning curve remain. Ongoing advancements are expected to further enhance these systems' role in spinal surgery.

Abstract Excessive intake of red meat may cause damage to colorectal tissue but not cause significant damage to the small intestine. However, the underlying mechanism is not clear. In this study, the effect of myoglobin extracted from red meat was explored on the intestinal barrier function of the mice, and its potential mechanism was elucidated through cell culture experiments. Exclusively high‐dose myoglobin (3.39%, equivalent to 450 g red meat per day for human) resulted in marked intestinal permeability with increased levels of serum endotoxin, diamine oxidase, and d‐lactate but reduced the mRNA levels of tight junction proteins and mucin 2 in the duodenal and colonic tissues. The diet also increased free iron and heme levels in the duodenal and colonic tissues, leading to higher level of oxidative stress and inflammatory response. Metabolomic analysis of colonic contents showed that exclusively high‐dose myoglobin altered the relative content of indole and its derivatives, phenolic compounds, and 5‐hydroxy‐l‐tryptophan by regulating tryptophan metabolism and kynurenine cycle and destroying intestinal homeostasis. The very high myoglobin hydrolysate induced oxidative stress and apoptosis more seriously in HT29 cells than in INT407 cells, which could be the main reason for more severe colon injury. Nevertheless, normal low‐dose intake (0.38% myoglobin, equivalent to 50 g per day for human) did not show the above‐mentioned harmful effects. The findings provided a risk assessment for the dosage of red meat intake and new insights into the relationship between red meat intake and intestinal health.

Abstract Objectives Internships in the pharmacy departments of training hospitals represent a crucial stage in the professional development of pharmacy students. However, the quality of internship training varies significantly across training hospitals in China, and there is a lack of standardized readiness evaluation tools. Therefore, the purpose of this study was to develop a self-assessment tool to evaluate the preparedness of training hospitals for providing internship training. Methods This study employed an exploratory mixed-methods approach and was conducted in two phases. In the first phase, during 2021, focus groups were conducted with 16 interns from three tertiary hospitals in Henan Province. In 2022, 14 preceptors from tertiary hospitals in various provinces were interviewed either one-on-one or in focus groups. The interview data were analyzed using thematic analysis to compile a set of self-assessment indicators for internship training readiness. Subsequently, the initial draft of the self-assessment tool for internship training readiness was developed by integrating the indicators derived from the interviews and literature review. In the second phase, the Delphi method was utilized. In 2023, the experts participated in two rounds of correspondence (21 experts in the first round and 19 in the second round), and consensus was reached on the indicators of the self-assessment tool after the two rounds. Meanwhile, these experts assessed the current status of internship training in training hospitals across China. Results The qualitative findings of the first phase included five themes and 22 sub-themes, which were integrated with the indicators derived from the literature review to develop an initial indicator framework for the second phase. This initial framework comprised five domains and 37 items. The second phase involved two rounds of expert surveys, with effective response rates of 90.48% and 89.47%, respectively. Ultimately, the self-assessment tool for evaluating the readiness of pharmacy departments in training hospitals for internships included five dimensions and 35 secondary indicators: (1) organizational structure, (2) training content, (3) training mode, (4) effectiveness evaluation, and (5) emergency management. Additionally, experts assessed the readiness of pharmacy departments in Chinese training hospitals for internships, yielding varied results. Emergency management preparedness scored the highest, followed by organizational structure and training content preparation. However, the modes of internship training and the evaluation of training effectiveness received lower scores. Conclusion The developed tool provides a comprehensive self-assessment checklist for the pharmacy departments of training hospitals and possesses the potential to enhance the development of more effective internship training programs.

Abstract This study aimed to investigate the therapeutic potential of human adipose‐derived mesenchymal stem cells (hADSCs) modified with recombinant adeno‐associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate‐buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control‐hADSCs group), or rAAV VEGF165 vector (VEGF165‐hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium‐binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165‐hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain‐derived neurotrophic factor (BDNF) and glial cell‐derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV‐VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies.

Abstract Objective Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. Methods Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). Results The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. Conclusion The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

Abstract. Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

BackgroundTo date, the differentiated requirements for network performance in various health care service scenarios—within, outside, and between hospitals—remain a key challenge that restricts the development and implementation of digital medical services. ObjectiveThis study aims to construct and implement a private 5G (the 5th generation mobile communication technology) standalone (SA) medical network in a smart health environment to meet the diverse needs of various medical services. MethodsBased on an analysis of network differentiation requirements in medical applications, the system architecture and functional positioning of the proposed private 5G SA medical network are designed and implemented. The system architecture includes the development of exclusive and preferential channels for medical use, as well as an ordinary user channel. A 3-layer network function architecture is designed, encompassing resource, control, and intelligent operation layers to facilitate management arrangements and provide network open services. Core technologies, including edge cloud collaboration; service awareness; and slicing of access, bearer, and core networks, are employed in the construction and application of the 5G SA network. ResultsThe construction of the private 5G SA medical network primarily involves system architecture, standards, and security measures. The system, featuring exclusive, preferential, and common channels, supports a variety of medical applications. Relevant standards are adhered to in order to ensure the interaction and sharing of medical service information. Security is achieved through mechanisms such as authentication, abnormal behavior analysis, and dynamic access control. Three typical medical applications that rely on the 5G network in intrahospital, interhospital, and out-of-hospital scenarios—namely, mobile ward rounds, remote first aid, and remote ultrasound—were conducted. Testing of the 5G-enabled mobile ward rounds showed an average download rate of 790 Mbps and an average upload rate of 91 Mbps. Compared with 4G, the 5G network more effectively meets the diverse requirements of various business applications in prehospital emergency scenarios. For remote ultrasound, the average downlink rate of the 5G network is 4.82 Mbps, and the average uplink rate is 2 Mbps, with an average fluctuation of approximately 8 ms. The bandwidth, performance, and delay of the 5G SA network were also examined and confirmed to be effective. ConclusionsThe proposed 5G SA medical network demonstrates strong performance in typical medical applications. Its construction and application could lead to the development of new medical service models and provide valuable references for the further advancement and implementation of 5G networks in other industries, both in China and globally.

Skin psoriasis is defined as receiving external stimulation to activate skin dendritic cells (DCs) which can release interleukin 23 (IL-23) to interlink the innate and adaptive immunity as well as induce T helper 17 (Th17) cell differentiation leading to elevated production of interleukin 17 (IL-17) for keratinocytes over production. This autoimmune loop in psoriasis pathogenesis is influenced by G protein-coupled receptor (GPCR) signalling transduction, and in particular, function of adhesion molecule GPR97 in psoriasis endures to be utterly addressed. In this research, our team allocated GPR97 depletion (GPR97-/-), GPR97 conditional depletion on dendritic cell (DC-cKO), and keratin 14-conditional knockout (K14-cKO) mice models to explore the function of GPR97 which influences keratinocytes and skin immunity. It was found that significantly aggravated psoriasis-like lesion in GPR97-/- mice. In addition, hyperproliferative keratinocytes as well as accumulation of DCs and Th17 cells were detected in imiquimod (IMQ)-induced GPR97-/- mice, which was consistent with the results in DC-cKO and K14-cKO psoriasis model. Additional investigations indicated that beclomethasone dipropionate (BDP), an agonist of GPR97, attenuated the psoriasis-like skin disease and restricted HaCaT cells abnormal proliferation as well as Th17 cells differentiation. Particularly, we found that level of NF-κB p65 was increased in GPR97-/- DCs and BDP could inhibit p65 activation in DCs. Role of GPR97 is indispensable and this adhesion receptor may affect immune cell enrichment and function in skin and alter keratinocytes proliferation as well as differentiation in psoriasis.

Abstract The risk for suffering immune checkpoint inhibitors (ICIs)‐associated myocarditis increases in patients with pre‐existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single‐cell RNA sequencing, and flow cytometry are used to decipher how anti‐cytotoxic T lymphocyte antigen‐4 m2a antibody (anti‐CTLA‐4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti‐CTLA‐4 m2a antibody increases cardiac fibroblast‐derived C‐X‐C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1‐Cxcr2 chemotaxis. It is identified that the C–C motif chemokine ligand 5 (Ccl5)‐neutrophil subpopulation is responsible for high activity of cytokine production, adaptive immune response, NF‐κB signaling, and cellular response to interferon‐gamma and that the Ccl5‐neutrophil subpopulation and its‐associated proinflammatory cytokines/chemokines promoted macrophage (Mφ) polarization to M1 Mφ. These altered infiltrating landscape and phenotypic switch of immune cells, and proinflammatory factors synergistically aggravated anti‐CTLA‐4 m2a antibody‐induced cardiac injury in EAM mice. Neutralizing neutrophils, Cxcl1, and applying Cxcr2 antagonist dramatically alleviates anti‐CTLA‐4 m2a antibody‐induced leukocyte infiltration, cardiac fibrosis, and dysfunction. It is suggested that Ccl5‐neutrophil subpopulation plays a critical role in aggravating anti‐CTLA‐4 m2a antibody‐induced cardiac injury in EAM mice. This data may provide a strategic rational for preventing/curing ICIs‐associated myocarditis.

Abstract Backgrounds The ossification of the ligamentum flavum (OLF) is one of the major causes of thoracic myelopathy. Previous studies indicated there might be a potential link between metabolic disorder and pathogenesis of OLF. The aim of this study was to determine the potential role of metabolic disorder in the pathogenesis of OLF using the strict bioinformatic workflow for metabolism‐related genes and experimental validation. Methods A series of bioinformatic approaches based on metabolism‐related genes were conducted to compare the metabolism score between OLF tissues and normal ligamentum flavum (LF) tissues using the single sample gene set enrichment analysis. The OLF‐related and metabolism‐related differentially expressed genes (OMDEGs) were screened out, and the biological functions of OMDEGs were explored, including the Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and protein–protein interaction. The competing endogenous RNA (ceRNA) network based on pairs of miRNA‐hub OMDEGs was constructed. The correlation analysis was conducted to explore the potential relationship between metabolic disorder and immunity abnormality in OLF. In the end, the cell experiments were performed to validate the roles of GBE1 and TNF‐α in the osteogenic differentiation of LF cells. Results There was a significant difference of metabolism score between OLF tissues and normal LF tissues. Forty‐nine OMDEGs were screened out and their biological functions were determined. The ceRNA network containing three hub OMDEGs and five differentially expressed miRNAs (DEmiRNAs) was built. The correlation analysis between hub OMDEGs and OLF‐related infiltrating immune cells indicated that metabolic disorder might contribute to the OLF via altering the local immune status of LF tissues. The cell experiments determined the important roles of GBE1 expression and TNF‐α in the osteogenic differentiation of LF cells. Conclusions This research, for the first time, preliminarily illustrated the vital role of metabolic disorder in the pathogenesis of OLF using strict bioinformatic algorithms and experimental validation for metabolism‐related genes, which could provide new insights for investigating disease mechanism and screening effective therapeutic targets of OLF in the future.

Abstract Background It was reported the paraspinal muscle played an important role in spinal stability. The preoperative paraspinal muscle was related to S1 screw loosening. But the relationship between preoperative and postoperative change of psoas major muscle (PS) and S1 pedicle screw loosening in degenerative lumbar spinal stenosis (DLSS) patients has not been reported. This study investigated the effects of preoperative and follow-up variations in the psoas major muscle (PS) on the first sacral vertebra (S1) screw loosening in patients with DLSS. Methods 212 patients with DLSS who underwent lumbar surgery were included. The patients were divided into the S1 screw loosening group and the S1 screw non-loosening group. Muscle parameters were measured preoperatively and at last follow-up magnetic resonance imaging. A logistic regression analysis was performed to investigate the risk factors for S1 screw loosening. Results The S1 screw loosening rate was 36.32% (77/212). The relative total cross-sectional areas and relative functional cross-sectional areas (rfCSAs) of the PS at L2–S1 were significantly higher after surgery. The increased rfCSA values of the PS at L3–S1 in the S1 screw non-loosening group were significantly higher than those in the S1 screw loosening group. The regression analysis showed male, lower CT value of L1 and longer segment fusion were independent risk factors for S1 screw loosening, and postoperative hypertrophy of the PS was a protective factor for S1 screw loosening. Conclusions Compared to the preoperative muscle, the PS size increased and fatty infiltration decreased after surgery from L2–3 to L5–S1 in patients with DLSS after short-segment lumbar fusion surgery. Postoperative hypertrophy of the PS might be considered as a protective factor for S1 screw loosening. MRI morphometric parameters and postoperative selected exercise of PS for DLSS patients after posterior lumbar fusion surgery might contribute to improvement of surgical outcome.

Abstract Background This study aimed to analyze the trends of Parkinson’s disease (PD) mortality rates among Chinese residents from 2004 to 2021, provide evidence for the formulation of PD prevention and control strategies to improve the quality of life among PD residents. Methods Demographic and sociological data such as gender, urban or rural residency and age were obtained from the National Cause of Death Surveillance Dataset from 2004 to 2021. We then analyzed the trends of PD mortality rates by Joinpoint regression. Results The PD mortality and standardized mortality rates in China showed an overall increasing trend during 2004–2021 (average annual percentage change [AAPC] = 7.14%, AAPCASMR=3.21%, P 85 years was the highest. Considering gender, female aged > 85 years had the fastest mortality trend (annual percentage change [APC] = 5.69%, P 85 years were risk factors for PD-related death and should be the primary focus for PD prevention.

Abstract Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect. Mechanistically, mitochondrial translocation of DJ-1 promoted the recruitment of hexokinase 2 (HK2) to damaged mitochondria by activating Akt and subsequently Parkin-dependent mitophagy to inhibit oxidative stress-induced apoptosis in NPCs. However, silencing Parkin, reducing mitochondrial recruitment of HK2, or inhibiting Akt activation suppressed DJ-1-mediated mitophagy. Furthermore, overexpression of DJ-1 ameliorated IDD in rats through HK2-mediated mitophagy. Taken together, these findings indicate that DJ-1 promotes HK2-mediated mitophagy under oxidative stress conditions to inhibit mitochondria-dependent apoptosis in NPCs and could be a therapeutic target for IDD.

Background The prevalence of combinations of comorbidities and their associations with inpatient service utilization and readmission among patients with chronic obstructive pulmonary disease (COPD) have not been extensively examined. To address this gap in knowledge, an observational prospective study was conducted using retrospective data.Aims To identify patterns of comorbidities linked to length of hospital stay, daily expenses, and one-year readmission.Methods The 30 most common comorbidities were identified in patients with secondary diagnoses using the association rule mining (ARM) method. Regression models were used to examine the relationships between combinations of comorbidities and service utilization, with adjustments for covariates.Results The five most prevalent comorbidities were pulmonary heart disease (40.99%), ischemic heart disease (38.97%), heart failure (36.77%), hypertension (34.11%), and respiratory disorders (19.12%). Most combinations of comorbidities identified by ARM showed significant associations with an extended length of stay (>13 days), increased daily expenses (>930 CNY), and reduced readmission rates. Among these combinations, glycoprotein metabolism disorder had the strongest association with prolonged length of stay (adjusted odds ratio [aOR]): 1.89, 95% confidence interval [CI]: 1.82–1.95). Conversely, the combination of other brain diseases and respiratory failure was linked to higher daily expenses (aOR: 11.34, 95% CI: 10.58–12.15), and the presence of pulmonary heart disease was associated with elevated one-year readmission rates (aOR: 1.41, 95% CI: 1.37–1.46).Conclusion Common combinations of comorbidities among inpatients with COPD were identified from an extensive collection of discharge medical records. Furthermore, the associations between comorbidities, inpatient service usage, and readmission rates were determined.

Accurate information on gross domestic product (GDP) is essential for better understanding the dynamics of regional economies and urbanization processes. Satellite based nighttime light datasets can well track GDP in urban areas, however, they are difficult to be used in suburban, rural and sparsely populated areas. Thus, this study explored the potential of GlobeLand30 and relief degree for improving the ability of VIIRS Nighttime Light data of GDP estimation. Firstly, we calculated the Moran’s Index (Moran’s I) to measure spatial auto-correlation of GDP. At provincial level, Moran’s I Index of GDP is 0.14, Z value is 2.29. While at the prefecture city level, it is 0.11 and 14.54, respectively. Then, we compared the results derived from geographically weighted regression (GWR) and OLS models (i.e., R2, root mean square error, corrected Akaike information criteria and residuals). Both models suggest that land cover information can significantly improve GDP estimation performance, and total nighttime light (TNL) is the most important economic indicator for estimating GDP. The coefficients of the GWR model for TNL at the provincial and prefecture levels are 1.75 and 1.19, respectively, which are significantly larger than the coefficients for other factors such as land cover and terrain undulation. In addition, the GWR model performed better than OLS model in GDP estimation at both provincial and prefecture levels, and prefecture-level models can better depict the spatial variation in detail. In provincial-level models, GWR could account for 93% of economic development, while OLS could only reflect 82%. Likewise, in prefecture-level models, R2 of GWR model improved almost 50% compared with that of OLS model.

In digital pathology, whole-slide images (WSIs) are widely used for applications such as cancer diagnosis and prognosis prediction. Vision transformer (ViT) models have recently emerged as a promising method for encoding large regions of WSIs while preserving spatial relationships among patches. However, due to the large number of model parameters and limited labeled data, applying transformer models to WSIs remains challenging. In this study, we propose a pretext task to train the transformer model in a self-supervised manner. Our model, MaskHIT, uses the transformer output to reconstruct masked patches, measured by contrastive loss. We pre-trained MaskHIT model using over 7000 WSIs from TCGA and extensively evaluated its performance in multiple experiments, covering survival prediction, cancer subtype classification, and grade prediction tasks. Our experiments demonstrate that the pre-training procedure enables context-aware understanding of WSIs, facilitates the learning of representative histological features based on patch positions and visual patterns, and is essential for the ViT model to achieve optimal results on WSI-level tasks. The pre-trained MaskHIT surpasses various multiple instance learning approaches by 3% and 2% on survival prediction and cancer subtype classification tasks, and also outperforms recent state-of-the-art transformer-based methods. Finally, a comparison between the attention maps generated by the MaskHIT model with pathologist's annotations indicates that the model can accurately identify clinically relevant histological structures on the whole slide for each task.

Abstract Background Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. Methods Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-β were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. Results In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1 −/− rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-β, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic β cells. Conclusions Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.

BackgroundIntestinal malrotation is a rare condition, and its delayed diagnosis can lead to fatal consequences. This study aimed to investigate the identification and treatment of malrotation in children.MethodsClinical data, imaging, operative findings, and early postoperative outcomes of 75 children with malrotation were retrospectively analyzed.ResultsThe mean age was 6.18 ± 4.93 days and 51.26 ± 70.13 months in the neonatal group (56 patients) and non-neonatal group (19 patients), respectively. Sixty-seven patients were under the age of 1 year at the time of diagnosis. The occurrence of bilious vomiting and jaundice was significantly higher in the neonatal group (89.29%) than that in the non-neonatal group (37.5%), p 10% of neonates and nearly 40% of non-neonates. This highlights the importance for emergency physicians and surgeons to be cautious about ruling out malrotation in patients with non-bilious vomiting. Utilizing US can obviate the need for contrast examinations owing to its higher diagnostic accuracy and rapid diagnosis and can be recommended as a first-line imaging technique. Additionally, open surgery is still an option for neonatal patients.

Background Retinal ischemic perivascular lesions (RIPLs) are an indicator of ischemia in the middle retina. We aimed to determine the relationship between RIPLs and single subcortical infarction (SSI). We also investigated the differences in cerebral small vessel disease imaging burden between groups with and without RIPLs in SSI. Methods and Results In this case–control study, we enrolled 82 patients with SSI and 72 nonstroke controls. All participants underwent magnetic resonance imaging and swept‐source optical coherence tomography/optical coherence tomography angiography. Small vessel disease markers such as lacunes, cerebral microbleeds, white matter hyperintensity, and perivascular spaces were rated on brain imaging. RIPLs were assessed via swept‐source optical coherence tomography. Optical coherence tomography angiography was used to measure the superficial vascular complex and deep vascular complex of the retina. After adjusting for risk factors, the presence of RIPLs was significantly associated with SSI (odds ratio [OR], 1.506 [95% CI, 1.365–1.662], P

Caspase (CASP) is a family of proteases involved in cleavage and activation of gasdermin, the executor of pyroptosis. In humans, CASP3 and CASP7 recognize the same consensus motif DxxD, which is present in gasdermin E (GSDME). However, human GSDME is cleaved by CASP3 but not by CASP7. The underlying mechanism of this observation is unclear. In this study, we identified a pyroptotic pufferfish GSDME that was cleaved by both pufferfish CASP3/7 and human CASP3/7. Domain swapping between pufferfish and human CASP and GSDME showed that the GSDME C-terminus and the CASP7 p10 subunit determined the cleavability of GSDME by CASP7. p10 contains a key residue that governs CASP7 substrate discrimination. This key residue is highly conserved in vertebrate CASP3 and in most vertebrate (except mammalian) CASP7. In mammals, the key residue is conserved in non-primates (e.g., mouse) but not in primates. However, mouse CASP7 cleaved human GSDME but not mouse GSDME. These findings revealed the molecular mechanism of CASP7 substrate discrimination and the divergence of CASP3/7-mediated GSDME activation in vertebrate. These results also suggested that mutation-mediated functional alteration of CASP probably enabled the divergence and specialization of different CASP members in the regulation of complex cellular activities in mammals.

IntroductionMeteorological and environmental factors can affect people’s lives and health, which is crucial among the older adults. However, it is currently unclear how they specifically affect the physical condition of older adults people.MethodsWe collected and analyzed the basic physical examination indicators of 41 older adults people for two consecutive years (2021 and 2022), and correlated them with meteorological and environmental factors. Partial correlation was also conducted to exclude unrelated factors as well.ResultsWe found that among the physical examination indicators of the older adults for two consecutive years, five indicators (HB, WBC, HbAlc, CB, LDL-C) showed significant differences across the population, and they had significantly different dynamic correlation patterns with six meteorological (air pressure, temperature, humidity, precipitation, wind speed, and sunshine duration) and seven air quality factors (NO2, SO2, PM10, O3-1h, O3-8h, CO, PM2.5).DiscussionOur study has discovered for the first time the dynamic correlation between indicators in normal basic physical examinations and meteorological factors and air quality indicators, which will provide guidance for the future development of policies that care for the healthy life of the older adults.

Abstract Background This study aimed to compare the postoperative quality of life (PQOL) between non–small–cell lung cancer (NSCLC) patients who underwent video–assisted thoracoscopic sublobar resection (subsegment, segment, or wedge) and lobectomy. Meanwhile, we developed a PQOL scale for patients with NSCLC after optimization. Methods Developing and evaluating the postoperative quality–of–life scale of non–small–cell lung cancer (NSCLC–PQOL) followed by the international principles for developing quality–of–life scale. Therefore, we used the NSCLC–PQOL scale to evaluate the PQOL of patients who underwent different surgeries. Results The overall PQOL of patients who underwent video-assisted thoracoscopic lobectomy and sublobar resection gradually worsened from discharge to 3 months postoperatively and progressively improved from three to 6 months postoperatively. And the sublobar resection group showed better PQOL in chest tightness, breath shortness, breathlessness, cough and expectoration than the lobectomy group, and the differences were statistically significant (P

Bladder cancer (BLCA) remains a difficult malignancy to manage because of its high recurrence, intense follow-up, and invasive diagnostic and treatment techniques. Immune checkpoint inhibitors (ICIs) have forged a new direction for the treatment of BLCA, but it is currently challenging to predict whether an individual patient will be sensitive to ICIs. We collected 43 urine/tumor samples from BLCA patients for primary bladder cancer cells (BCCs) culturing using our previously reported BCC culture platform. We used flow cytometry (FCM) to measure the expression levels of Programmed Death-Ligand 1 (PD-L1) on BCCs before and after interferon-gamma (IFN-γ) treatment and found that PD-L1 expression and the sensitivities to IFN-γ varied among patients. RNA-sequencing, western blotting, and programmed death-1 (PD-1) binding assays confirmed that the BCC FCM-based PD-L1 detection platform (BC-PD-L1) was reliable and was not hindered by the glycosylation of PD-L1. In the subsequent retrospective study, we found that IFN-γ-stimulated PD-L1 (sPD-L1) expression on BCCs detected by BC-PD-L1 could predict the prognosis of BLCA patients. Importantly, the prognostic value was similar or even better in urine-derived BC-PD-L1 (UBC-PD-L1). Transcriptome analysis showed that BCCs with high sPD-L1 tended to enrich genes associated with the collagen-containing extracellular matrix, cell–cell adhesion, and positive regulation of the immune system. In addition, the UBC-PD-L1 also exhibited predictive value for ICI response in BLCA patients. In conclusion, as a novel personalized urine-detection method, UBC-PD-L1 may provide a rapid, accurate, and non-invasive tool for monitoring tumor progression, predicting therapeutic responses, and helping improve BLCA clinical treatment in future.

Abstract Immunogenomic loci remain poorly understood because of their genetic complexity and size. Here, we report the de novo assembly of a cattle genome and provide a detailed annotation of the immunogenomic loci. The assembled genome contains 143 contigs (N50 ~ 74.0 Mb). In contrast to the current reference genome (ARS-UCD1.2), 156 gaps are closed and 467 scaffolds are located in our assembly. Importantly, the immunogenomic regions, including three immunoglobulin (IG) loci, four T-cell receptor (TR) loci, and the major histocompatibility complex (MHC) locus, are seamlessly assembled and precisely annotated. With the characterization of 258 IG genes and 657 TR genes distributed across seven genomic loci, we present a detailed depiction of immune gene diversity in cattle. Moreover, the MHC gene structures are integrally revealed with properly phased haplotypes. Together, our work describes a more complete cattle genome, and provides a comprehensive view of its complex immune-genome.

Abstract Background This study aimed to determine long-term variations in mortality trends and identify the leading causes of death among older adults in China from 2009 to 2019 so as to propose interventions to further stabilise the mortality rate among older adults and facilitate healthy ageing. Methods We extracted data from the China Death Surveillance database from 2009 to 2019 for all-cause mortality and cause-specific death among individuals aged ≥ 65 years. A joinpoint regression model was used to estimate mortality trends by calculating the annual percentage change (APC). A trend chi-square test was used to estimate sex differences in mortality, and descriptive analysis was used to estimate the leading causes of death. Semi-structured expert interviews were conducted to examine health interventions for older adults. Results We observed an overall declining trend in age-adjusted mortality rates among older adults aged ≥ 65 years in China from 2009 to 2019 (APC, -2.44; P

The increasing proliferation of space debris, intermittent space incidents, and the rapid emergence of massive LEO satellite constellations pose significant threats to satellites in orbit. Ground-based optical observations play a crucial role in space surveillance and space situational awareness (SSA). The Zhulong telescopic observation network stands as a pivotal resource in the realm of space object tracking and prediction. This publicly available network plays a critical role in furnishing essential data for accurately delineating and forecasting the orbit of space objects in Earth orbit. Comprising a sophisticated array of hardware components including precise telescopes, optical sensors, and image sensors, the Zhulong network synergistically collaborates to achieve unparalleled levels of precision in tracking and observing space objects. Central to the network’s efficacy is its ability to extract positional information, referred to as angular data, from consecutive images. These angular data serve as the cornerstone for precise orbit determination and prediction. In this study, the CPF (Consolidated Prediction Format) orbit serves as the reference standard against which the accuracy of the angular data is evaluated. The findings reveal that the angular data error of the Zhulong network remains consistently below 3 arcseconds, attesting to its remarkable precision. Moreover, through the accumulation of angular data over time, coupled with the utilization of numerical integration and least squares methods, the Zhulong network facilitates highly accurate orbit determination and prediction for space objects. These methodologies leverage the wealth of data collected by the network to extrapolate trajectories with unprecedented accuracy, offering invaluable insights into the behavior and movement of celestial bodies. The results presented herein underscore the immense potential of electric optic telescopes in the realm of space surveillance. By harnessing the capabilities of the Zhulong network, researchers and astronomers can gain deeper insights into the dynamics of space objects, thereby advancing our understanding of the cosmos. Ultimately, the Zhulong telescopic observation network emerges as a pioneering tool in the quest to unravel the mysteries of the universe.

AIM: To report the clinical characteristics, treatment and outcomes of active syphilitic uveitis in human immunodeficiency virus (HIV) positive patients and compare them with the previously published data. METHODS: Retrospective analysis of the case series from an infectious disease center in southern China was conducted. Comprehensive review of previously published cases of HIV positive syphilitic uveitis was conducted using the PubMed and Web of Science databases and the references listed in the identified articles. RESULTS: Twelve HIV positive patients with active syphilitic uveitis were collected. All were male, with age of 36.3y (range 27 to 53y). Five (41.7%) had a history of syphilis, and three of them had received anti-syphilis treatment. Ocular manifestations included corneal epithelial defect (13%), complicated cataract (17.4%), vitreous opacity (82.6%), optic disc edema (26.1%), macular edema (30.4%), neuro-retinitis (43.5%), and retinal hemorrhage (26.1%). After standardized syphilitic treatment, intraocular inflammation was reduced and vision improved in all cases. The literature review summarizes 105 previously reported cases of HIV positive syphilitic uveitis. High serum rapid plasma regain (RPR) titers may be associated with severe uveitis and poor vision. Treatment with penicillin, ceftriaxone sodium, or penicillin plus benzylpenicillin instead of using benzylpenicillin alone can significantly improve best-corrected visual acuity (BCVA) in HIV positive ocular syphilis patients. CONCLUSION: For HIV positive syphilitic uveitis patients, prompt diagnosis and appropriate treatment and follow-up are paramount. In our series, the clinical manifestations are diverse. Syphilis patients treated by penicillin G or long-acting penicillin before may still develop syphilitic uveitis. Patients who relapse after long-term penicillin treatment can still benefit from penicillin G.

Abstract Background This study aimed to examine the bidirectional relationship between social isolation and cognitive performance among Chinese middle-aged and older adults. Methods We used four waves of data from the China Health and Retirement Longitudinal Study. A latent growth model (LGM) was applied to examine the association between social isolation and cognitive performance across different characteristics. Results In the analysis, we ultimately included 9,367 participants after excluding respondents with missing key variables. Social isolation and cognitive performance showed significant differences across time. After adjusting for the confounders, there was a significant association between higher social isolation and poor cognitive performance (β = −1.38, p

Based on field investigation, InSAR, GNSS monitoring, and deep displacement monitoring, a deformed loess landslide in Lingwan Village, Yujiaping Town, West-East Gas Pipeline Project was analyzed to understand its deformation characteristics and landslide formation mechanism from 2017 to 2022. The analysis shows that the groundwater level of the landslide has reached the toe of the slope, and numerous soil slips have been formed at the front edge of the landslide. The surface of the landslide exhibits vertical subsurface erosion cracks, while the penetrating cracks can be seen at the trailing edge. InSAR data shows that the landslide has been slowly deformed, with an annual deformation rate between 2.0 - 4.0 cm. GNSS deformation and crack deformation show that since August 2020, the surface deformation rate has increased significantly, with a deformation rate between 4.0 - 10.0 cm. The variation of deep deformation monitoring data is minimal, between 0.05 to 1.36 mm. Analysis of rainfall and soil moisture data shows that the landslide has displacement deformation after rainstorm. The comprehensive analysis of monitoring data reveals that the landslide in Lingwan Village is a shallow landslide induced by rainfall. Natural heavy rainfall and human engineering economic activities in the region are the primary inducing factors for the occurrence and development of landslide. Combined with pipeline strain monitoring data, the risk of landslide disasters in Shaanxi Province section of West-East Gas Pipeline Project is controllable.

Abstract Background Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle‐invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD‐1 blockade, has shown benefits in several tumors. This study aimed to investigate the efficacy and safety of neoadjuvant camrelizumab in combination with gemcitabine plus cisplatin (GC) followed by RC for MIBC patients. Methods This was a multi‐center, single‐arm study that enrolled MIBC patients with a clinical stage of T2‐4aN0‐1M0, and scheduled for RC. Patients received three 21‐day cycles of camrelizumab 200 mg on day 1, gemcitabine 1000 mg/m2 on day 1 and 8, and cisplatin 70 mg/m2 on day 2, followed by RC. The primary endpoint was pathologic complete response (pCR, pT0N0). Results From May 2020 to July 2021, 43 patients were enrolled and received study medications at nine centers in China. Three of them were deemed ineligible and excluded from efficacy analysis but included in safety analysis. In total 10 patients were unevaluable as they declined RC (two due to adverse events [AEs] and eight due to patient's willingness). Among 30 evaluable patients, 13 patients (43.3%) achieved pCR, and 16 patients (53.3%) achieved pathologic downstaging. No AEs leading to death were observed. The most common AEs were anemia (69.8%), decreased white blood cell count (65.1%), and nausea (65.1%). Immune‐related AEs were all grade 1 or 2. Pathologic response was not correlated with PD‐L1 expression status or tumor mutation burden. Individual genes as a biomarker for pathologic response were not identified. Conclusions Neoadjuvant treatment with camrelizumab and GC regimen demonstrated preliminary anti‐tumor activity for MIBC patients with manageable safety profiles. The study met its primary endpoint, and the following randomized trial is ongoing.

Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins, antibodies, and even cells. The study in Nature by Chang and Toste introduces a redox-based strategy for tryptophan bioconjugation, employing N-sulfonyloxaziridines as oxidative cyclization reagents, demonstrating high efficiency comparable to traditional click reactions. Meanwhile, this tool provides feasible methods for investigating the mechanisms underlying functional tryptophan-related biochemical processes, paving the way for protein function exploration, activity-based proteomics for functional amino acid identification and characterization, and even the design of covalent inhibitors.

BackgroundTelemedicine has demonstrated its potential in alleviating the unbalanced distribution of medical resources across different regions. Henan, a province in China with a population of approximately 100 million, is especially affected by a health care divide. The province has taken a proactive step by establishing a regional collaborative platform for telemedicine services provided by top-tier provincial hospitals. ObjectiveWe aim to identify the key factors that influence the current operationalization and effectiveness of telemedicine services in Henan province. The insights gained from this study will serve as valuable references for enhancing the efficient operation of telemedicine platforms in low- and middle-income regions. MethodsWe analyzed service reports from the performance management system of telemedicine services in Henan province throughout 2020. Using descriptive statistics and graphical methods, we examined key influencing factors, such as management competency; device configuration; and hospital capability, capacity, and service efficacy, across hospitals at 2 different tiers. In addition, we used generalized linear models and multiple linear regression models to identify key operational factors that significantly affect the service volume and efficacy of 2 major telemedicine services, namely teleconsultation and tele-education. ResultsAmong the 89 tier 3 hospitals and 97 tier 2 hospitals connected to the collaborative telemedicine platform, 65 (73%) and 55 (57%), respectively, have established standardized management procedures for telemedicine services. As the primary delivery method for telemedicine services, 90% (80/89) of the tier 3 hospitals and 94% (91/97) of the tier 2 hospitals host videoconferencing consultations through professional hardware terminals rather than generic computers. Teleconsultation is the dominant service type, with an average annual service volume per institution of 173 (IQR 37-372) and 60 (IQR 14-271) teleconsultations for tier 3 and tier 2 hospitals, respectively. Key factors influencing the service volume at each hospital include available funding, management competency, the number of connected upper tiers, and the number of professional staff. After receiving teleconsultations from tier 3 (65/89, 73%) and tier 2 (61/97, 63%) hospitals, patients reported significant improvements in their medical conditions. In addition, we observed that service efficacy is positively influenced by management competency, financial incentives, the number of connected upper or lower tiers, and the involvement of participating medical professionals. ConclusionsTelemedicine has become increasingly popular in Henan province, with a notable focus on teleconsultation and tele-education services. Despite its popularity, many medical institutions, especially tier 2 hospitals, face challenges related to management competency. In addition to enhancing the effectiveness of existing telemedicine services, health care decision-makers in Henan province and other low- and middle-income regions should consider expanding the service categories, such as including remote emergency care and telesurgery, which have promise in addressing crucial health care needs in these regions.

ObjectiveTo assess the overall effectiveness of non-pharmacological interventions on internet addiction (IA) in youth.MethodRandomized controlled trials (RCTs) published from their inception to April 1, 2023 were searched in Cochrane, Embase, Medline, Web of Science, China National Knowledge Infrastructure, China Science and Technology Journal Database, Chinese BioMedical Literature Database, and WanFang Data. Two reviewers independently extracted data and evaluated bias using the Cochrane Risk of Bias tool.ResultsSixty-six studies performed from 2007 to 2023, with a total of 4,385 participants, were identified. The NPIs included group counseling, cognitive behavioral therapy, sports intervention, combined interventions, eHealth, educational intervention, positive psychology intervention, sand play intervention, and electrotherapy. The results revealed that NPIs significantly reduced IA levels (standardized mean difference, SMD: −2.01, 95% confidence interval, CI: −2.29 to −1.73, I2 = 93.0%), anxiety levels (SMD: −1.07, 95%CI: −1.41 to −0.73, I2 = 72.4%), depression levels (SMD: −1.11, 95%CI: −1.52 to −0.7, I2 = 84.3%), and SCL-90 (SMD: −0.75, 95%CI: −0.97 to −0.54, I2 = 27.7%). Subgroup analysis stratified by intervention measure showed that cognitive behavioral therapy, group counseling, sports intervention, combined intervention, educational intervention, positive psychology intervention, sandplay intervention, and mobile health were all effective in relieving symptoms of IA except electrotherapy.ConclusionNPIs appear to be effective in the treatment of IA in youth, which would act as an alternative treatment of IA. Further studies with larger sample sizes and robust designs are needed.