BackgroundThe violent aggressive behaviors of patients with schizophrenia usually have the characteristics of suddenness， unpredictability， high severity， and great difficulty in prevention. Early identification and accurate assessment of their risk of violent aggression have significant clinical significance. ObjectiveTo construct a predictive model for the violence risk in hospitalized patients with schizophrenia， to identify the key factors influencing the occurrence of violent behavior in these patients， so as to provide references for clinical precise quantitative assessment and early intervention. MethodsA total of 200 patients with schizophrenia who were hospitalized at Taiyuan Psychiatric Hospital from March 2022 to September 2024 and met the diagnostic criteria of the International Classification of Diseases， eleventh edition （ICD-11） were collected to form the modeling cohort. They were randomly divided into a training set （n=140） and a test set （n=60） at a ratio of 7∶3. Based on the least absolute shrinkage and selection operator （LASSO） regression algorithm， the feature variables were screened and dimension-reduced. The support vector machine （SVM） from machine learning was selected for model training and prediction. The discrimination efficacy of the model was evaluated by the area under the receiver operating characteristic （ROC） curve （AUC）， accuracy， precision， sensitivity， specificity， F1 value， and Brier value. ResultsLASSO regression screening identified 16 feature variables. Pearson correlation analysis revealed a positive correlation between prior violent behavior frequency and clinical psychiatric symptom scores （r=0.580， P<0.01）， a positive correlation between hospitalization compliance and current disease status （r=0.550， P=0.003）， and a positive correlation between educational level and family per capita monthly income （r=0.367， P<0.01）. The SVM model achieved an AUC of 0.853， accuracy of 0.800， precision of 0.810， sensitivity of 0.895， specificity of 0.636， F1 value of 0.850， and Brier value of 0.168. ConclusionThe SVM model has a relatively high level of applicability and overall predictive performance in the assessment of violent risk in schizophrenia patients， which is helpful for the early identification of violent risks in such patients. ［Funded by Specialized Research Project for Enhancing the Competence of Health Professionals in Taiyuan City （number， Y2023006）］

Osteoporosis is a common senile bone metabolism disease， clinically characterized by decreased bone mass， destruction of bone microstructure， increased bone fragility， and easy fracture. It tends to occur in the elderly and postmenopausal women， seriously threatening the quality of life and physical and mental health of the elderly. At present， the treatment of osteoporosis is mainly based on oral western medicines， such as calcium， Vitamin D， and bisphosphonates. Still， there are drawbacks such as a long medication cycle and many adverse reactions. In recent years， due to the advantages of multi-component， multi-pathway， and multi-target， some traditional Chinese medicines and effective ingredients can regulate the osteogenic and osteoclastic differentiation process in both directions and are widely used in the prevention and treatment of osteoporosis. Hippophae rhamnoides is a commonly used herbal medicine， and its fruits are rich in flavonoids， polyphenols， fatty acids， vitamins， and trace elements， which have been proven to have a good anti-osteoporosis effect. Isorhamnetin is the main effective ingredient of Hippophae rhamnoides fruits， which has many pharmacological effects such as anti-inflammation， anti-oxidative stress， anti-aging， and anti-tumor. Studies have shown that isorhamnetin can participate in the regulation of bone metabolism and has a good anti-osteoporosis effect. However， the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis have not been systematically summarized. Therefore， this paper reviewed the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis by referring to relevant literature to provide more basis for the development and application of isorhamnetin.

ObjectiveTo investigate the mechanism by which Mingshi prescription regulates the retinal melanopsin-dopamine （Opn4-DA） axis in myopic mice to inhibit endoplasmic reticulum （ER） stress in the retina and sclera， thereby delaying axial elongation associated with myopia. MethodsSixty 4-week-old male SPF-grade C57BL/6J mice were randomly divided into a normal group， a form-deprived myopia group （FDM group）， an intrinsically photosensitive retinal ganglion cells ablation group （ipRGCs group）， a Mingshi Prescription group （MSF group， 5.2 g·kg^-1）， and an ipRGCs + MSF group （5.2 g·kg^-1）. Except for the normal group， all other groups underwent FDM modeling. Additionally， the ipRGCs and ipRGCs + MSF groups received retinal ipRGC ablation. Three weeks after modeling， the MSF and ipRGCs + MSF groups were administered Mingshi prescription via continuous gavage for six weeks. After refraction and axial length were measured in all mice， eyeballs were collected along with retinal and scleral tissues. Pathological and morphological changes in the retina， choroid， and sclera were observed using periodic acid-Schiff （PAS） staining. Western blot was employed to detect the relative protein expression levels of dopamine D1 receptor （DRD1）， C/EBP homologous protein （CHOP）， and glucose-regulated protein 78 （GRP78） in the retina， and CHOP and GRP78 in the sclera. Real-time PCR was used to detect the relative mRNA expression of Opn4， CHOP， and GRP78 in the retina， and CHOP and GRP78 in the sclera. Immunofluorescence staining （IF） was performed to detect the expression of Opn4 and DRD1 in retinal tissues. ResultsCompared with the normal group， the FDM group showed a significant myopic shift in refraction （P<0.05） and a significant increase in axial length （P<0.05）. The retinal layers were thinner， the number of ganglion cells was reduced， and collagen fibers in the sclera were loosely arranged with evident gaps. Opn4 and DRD1 protein and mRNA expression in the retina were significantly decreased （P<0.05）， while CHOP and GRP78 protein and mRNA expression in both retinal and scleral tissues were significantly increased （P<0.05）. Compared with the FDM group， the ipRGCs group exhibited further increases in myopic refraction and axial length （P<0.05）， more pronounced thinning and looseness in the retinal， choroidal， and scleral layers， lower expression of Opn4 and DRD1 protein and mRNA in the retina （P<0.05）， and higher expression of CHOP and GRP78 protein and mRNA in the retina and sclera （P<0.05）. Compared with the FDM group， the MSF group showed significantly reduced refractive error and axial length （P<0.05）， with improved cellular number， arrangement， and thickness in ocular tissues， increased Opn4 and DRD1 protein and mRNA expression in the retina （P<0.05）， and reduced CHOP and GRP78 protein and mRNA expression in both retina and sclera （P<0.05）. Similarly， the ipRGCs + MSF group showed significant improvements in terms of the above items compared with the ipRGCs group （P<0.05）. ConclusionMingshi Prescription delays myopic axial elongation and refractive progression by regulating the Opn4-DA axis in the retina of myopic mice， thereby inhibiting ER stress in the retina and sclera. This intervention promotes Qi and blood nourishment of the eyes， softens the fascia， and restores ocular rhythm.

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

As global greenhouse gases continue rising, the urgency of more ambitious action is clearer than ever before. China is the world's biggest emitter of greenhouse gases and one of the countries affected most by climate change. The evidence about the impacts of climate change on the environment and human health may encourage China to take more decisive action to mitigate greenhouse gas emissions and adapt to climate impacts. This article aimed to review the evidence of environmental damages and health risks posed by climate change and to provide a new science-based perspective for the delivery of sustainable development goals. Over recent decades, China has experienced a strong warming pattern with a growing frequency of extreme weather events, and the impacts of climate change on China's environment and human health have been consistently observed, with increasing O ₃ air pollution, decreases in water resources and availability, land degradation, and increased risks for both communicable and non-communicable diseases. Therefore, China's climate policy should target the key factors driving climate change and scale up strategic measures to curb carbon emissions and adapt to inevitable increasing climate impacts. It provides new insights for not only China but also other countries, particularly developing and emerging economies, to ensure climate and environmental sustainability whilst pursuing economic growth.
Climate Change ; China ; Humans ; Greenhouse Gases ; Air Pollution ; Sustainable Development ; Environment

Childhood primary renal tubular diseases are chronic kidney diseases characterized by impaired renal tubular reabsorption. Primary renal tubular disease has diverse clinical manifestations and lacks of specificity. Laboratory tests are limited，making it prone to missed diagnosis and misdiagnosis. Based on the current knowledge of renal tubular diseases，authors propose early warning signals of renal tubular diseases such as family history of primary tubular diseases，unexplained polyhydramnios during pregnancy，polydipsia，polyuria，delayed growth and development or rickets，decreased muscle strength and tone，unexplained electrolyte disturbance，hyperuricemia，acid-base disturbance，positive urine sugar test，renal tubular proteinuria，urinary imaging examination suggesting kidney stones，calcium deposition，renal cysts and early onset of eye，ear，joint and neuron injury.Meanwhile，some universal management strategies for primary renal tubular disease are proposed，emphasizing the importance of multidisciplinary collaboration，genetic testing and individualized intervention to improve the long-term prognosis of childhood primary renal tubular diseases.

Objective This study aimed to explore the spatial heterogeneity and risk factors for dental caries in 12-year-old children in Shanxi province,China. Methods The data encompassed 3,721 participants from the two most recent oral health surveys conducted across 16 districts in Shanxi Province in 2015 and 2018.Eighteen specific variables were analyzed to examine the interplay between socioeconomic factors,medical resources and environmental conditions.The Geo-detector model was employed to assess the impacts and interactions of these ecological factors. Results Socioeconomic factors(Q=0.30,P<0.05)exhibited a more substantial impact compared to environmental(Q=0.19,P<0.05)and medical resource factors(Q=0.25,P<0.05).Notably,the urban population percentage(UPP)demonstrated the most significant explanatory power for the spatial heterogeneity in caries prevalence,as denoted by its highest q-value(q=0.51,P<0.05).Additionally,the spatial distribution's heterogeneity of caries was significantly affected by SO2 concentration(q=0.39,P<0.05)and water fluoride levels(q=0.27,P<0.05)among environmental factors. Conclusion The prevalence of caries exhibited spatial heterogeneity,escalating from North to South in Shanxi Province,China,influenced by socioeconomic factors,medical resources,and environmental conditions to varying extents.

Objective:To analyze the clinical efficacy of internal fixation and prosthesis revision in the treatment of periprosthesis fracture after total knee arthroplasty.Methods:A total of 35 patients (35 knees) with periprosthetic fractures after total knee arthroplasty were retrospectively analyzed from January 2008 to January 2022 in the Department of Orthopaedics, West China Hospital, Sichuan University, including 13 males and 22 females, aged 71.4±4.1 years (range, 62-81 years). Left knee 19 cases, right knee 16 cases. There were 20 cases of Rorabeck type II and 15 cases of Rorabeck type III. The initial replacement was performed using a fixed platform post-stabilized knee prosthesis, which was fixed with bone cement. Patients with Rorabeck type II were treated with internal fixation alone (internal fixation group) and patients with Rorabeck type III underwent revision with replacement prosthesis (revision group). The Hospital for Special Surgery (HSS) score, range of motion (ROM) of knee joint, alignment of lower extremity and incidence of postoperative complications were compared between the two groups.Results:All patients successfully completed the operation and were followed up for 5.2±3.6 years (range, 1-12 years). Intraoperative blood loss was 680±102 ml (range, 420-1100 ml). The operative time in the internal fixation group was 105±17 min, which was less than 140±21 min in the revision group, and the difference was statistically significant ( t=-5.450, P<0.001). There was no complication of nerve or blood vessel injury during the operation. Five cases in the internal fixation group had unsatisfactory lower extremity force lines (>3° deviation from normal) after surgery, and all lower extremity force lines in the revision group were satisfied, and the difference in the satisfaction rate of lower extremity force lines between the two groups was not statistically significant ( P=0.057). The fracture healing time, knee ROM and HSS scores at the last follow-up were 5.1±1.3 months, 86°±5° and 84±5 in the internal fixation group and 4.8±1.5 months, 83°±6° and 82±4 in the revision group. One case in the revision group was diagnosed postoperatively with periprosthetic infection with pathogen culture suggestive of Candida albicans, recurrent anterior knee sinus tracts and patellar ectasia, which progressed to osteomyelitis, and mid-thigh amputation was performed 1 year after revision. Conclusion:The stability of prosthesis is an important reference for the treatment of periprosthetic fractures after total knee arthroplasty. Strong internal fixation in patients with unloosened prosthesis and revision with replacement of prosthesis in patients with loose prosthesis can achieve good knee joint function.