Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms such as bacteria. In addition to the manifestations of systemic inflammatory response syndrome and primary infection lesions， critical cases often have manifestations of organ hypoperfusion. The morbidity and mortality of sepsis have remained high in recent years， which seriously affect the quality of life of the patients. The pathogenesis of sepsis is complicated， in which uncontrollable inflammation is a key mechanism. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a key role in mediating inflammation in sepsis. The available therapies of sepsis mainly include resuscitation， anti-infection， vasoactive drugs， intensive insulin therapy， and organ support， which show limited effects of reducing the mortality. Therefore， finding new therapeutic drugs is a key problem to be solved in the clinical treatment of sepsis. In recent years， studies have shown that traditional Chinese medicine （TCM） can regulate the PI3K/Akt pathway via multiple pathways， multiple effects， and multiple targets to inhibit inflammation and curb the occurrence and development of sepsis， which has gradually become a hot spot in the prevention and treatment of sepsis. Moreover， studies have suggested that TCM has unique advantages in the treatment of sepsis. TCM can regulate the PI3K/Akt signaling pathway to inhibit inflammation， reduce oxidative stress， and control apoptosis in the prevention and treatment of sepsis. Despite the research progress， a systematic review remains to be performed regarding the TCM treatment of sepsis by regulating the PI3K/Akt signaling pathway. After reviewing relevant papers published in recent years， this study systematically summarizes the relationship between PI3K/Akt pathway and sepsis and the role of TCM in the treatment of sepsis， aiming to provide new ideas for the potential treatment of sepsis and the development of new drugs.

OBJECTIVE To provide technical support for improving recognition rate of adverse drug events （ADEs） related to traditional Chinese medicine （TCM） formula granules and decoction pieces among inpatient patients. METHODS By referencing the global trigger tool （GTT） whitepaper， literature on adverse reactions to TCM， and expert review opinions， ADE trigger items for TCM formula granules and decoction pieces used in the inpatients were established. GTT was applied to analyze ADEs in inpatients who had used TCM formula granules and decoction pieces in our hospital from August 2013 to August 2023， utilizing the Chinese Hospital Pharmacovigilance System. The effectiveness of GTT and the characteristics of these ADEs were analyzed. RESULTS A total of forty-eight triggers were established， including thirty-two laboratory test indexes， thirteen clinical symptoms， and three antidotes. Among the 1 682 patients included， GTT identified 652 potential ADEs， 284 true positive ADEs，with a trigger rate of 38.76% and a positive predictive value of 43.56%. After review by the auditor， 278 cases of ADEs were finally confirmed， with an incidence rate of 16.53%， significantly higher than the number of spontaneously reported ADEs during the same period （0）. The 278 cases of ADEs were mostly grade 1 （223 cases）， mainly involving hepatobiliary system， gastrointestinal system， blood- lymphatic system， etc；a total of 219 types of TCMs are involved，and the top five suspected TCMs used at a frequency higher than 1% were Poria cocos， Codonopsis pilosula， Atractylodes macrocephala， fried Glycyrrhiza uralensis， and Scutellaria baicalensis. CONCLUSIONS The established GTT can improve the recognition rate of ADEs for hospitalized patients using traditional Chinese medicine formula granules and decoction pieces.

ObjectiveTo explore the coercive experience of involuntarily hospitalized adolescents with mental disorders during the admission process and hospitalization， providing references for formulating targeted nursing interventions. MethodsSemi-structured interviews were conducted with 15 involuntarily hospitalized adolescents with mental disorders selected from October to December 2023， and the themes were summarized and extracted by content analysis. ResultsA total of 3 themes and 10 sub-themes were extracted， which were used to elaborate the essential contents， causes， and improvement methods of coercive experience. These encompassed the multi-dimensional content of coercive experience （complex emotional experience， different physical sensations， and contradictory cognitive evaluation）， the multi-faceted causes of coercive experience （insufficient personal preparation， inadequate parental communication， and strict medical management system）， as well as the phased improvement of coercive experience （adequate communication before hospitalization， patient notification before coercive intervention， respecting for demands during coercive intervention， and comforting explanation after coercive intervention）. ConclusionThe essential content of the coercive experience of involuntarily hospitalized adolescents with mental disorders is complex and has various causes， which require cooperation from multiple parties to improve. Therefore， parents should respect the expression of their children’s self-will， and medical staff should respect patients’ autonomy， establishing a protection-constrained doctor-patient relationship model and collaborating to reduce the use of coercive interventions， to improve the overall medical satisfaction of adolescents with mental disorders.

BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs) are common organic compounds in indoor and outdoor air, and enter the human body primarily through the respiratory tract and directly damage the respiratory system. Previous studies have suggested that exposure to VOCs/SVOCs may associate with the prevalence, incidence, and progression of asthma, but the extent of the associations is still vague. Furthermore, biomarkers for efficient and simple asthma diagnosis, typing, and attack prediction remain unclear at this stage. From the perspective of the collection and detection methods of VOCs/SVOCs, this paper summarized the epidemiological associations and underlying biological mechanisms between VOCs/SVOCs exposure and the prevalence, incidence, and progression of asthma in children/adults. It also demonstrated the application of VOCs/SVOCs in recent years in assisting asthma diagnosis, such as distinguishing asthma patients from the healthy population, differentiating different asthma phenotypes, and predicting asthma acute exacerbations, aiming to provide a scientific basis for improving current asthma management.

ObjectiveTo investigate the potential mechanisms of Zhimu （Anemarrhena asphodeloides）-Huangbai （Phellodendron amurense） medicinal pair in alleviating postmenopausal osteoporosis （PMOP）. MethodsSixty unpregnant female SD rats were randomly divided into five groups， blank group， model group， low-dose Zhimu-Huangbai group， high-dose Zhimu-Huangbai group， and estradiol group， with 12 rats in each group. Except for the blank group， all other groups had their ovaries removed to create PMOP rat models， while the blank group only had the fat tissue around the ovaries removed. One week after the ovarian removal， the low-dose and high-dose Zhimu-Huangbai groups received concentrated solution of Zhimu and Huangbai with 1.8， 7.2 g/（kg·d） via gavage， the estradiol group received estradiol solution 0.09 mg/（kg·d） via gavage， and the blank group and the model group received 10 ml/（kg·d） of normal saline via gavage， once daily for 12 weeks. Before sampling， the body mass of the rats was recorded， and uterine tissue was taken to calculate the uterine index. The levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum were detected by ELISA； micro CT was used to examine the parameters of femoral microstructure， including bone volume/tissue volume （BV/TV）， trabecular number （Tb.N）， trabecular thickness （Tb.Th）， bone mineral density （BMD）， trabecular separation （Tb.Sp）， and cortical bone area （Ct.Ar）. HE staining was used to observe pathological changes in the femur； RT-qPCR was used to detect the mRNA expression of osteogenic-adipogenic differentiation-related factors in femoral tissue， including Runt-related transcription factor 2 （Runx2）， bone morphogenetic protein 2 （BMP-2）， peroxisome proliferator-activated receptor γ （PPARγ）， chemerin and chemokine-like receptor 1 （CMKLR1）. ResultsCompared with the blank group， the model group showed a significant increase in body mass， a significant decrease in the uterine index， BV/TV， Tb.N， Tb.Th and BMD， a significant increase in Tb.Sp， and serum IL-1β， IL-6， and TNF-α levels， a significant reduction of mRNA expression of Runx2 and BMP-2 in bone tissue， and a significant increased mRNA expression of PPARγ， chemerin， and CMKLR1 （P＜0.01）. HE staining revealed that the femoral tissue showed a reduction and sparsity of trabeculae， a significant enlargement of the medullary cavity， and a large number of fat cells. Compared to the model group， the low-dose， high-dose Zhimu-Huangbai groups， and estradiol group showed significant improvements in all the above-mentioned indicators （P＜0.05 or P＜0.01）. HE staining revealed a significant increase in trabeculae， more organized arrangement， and a marked reduction in fat cells. Compared to low-dose Zhimu-Huangbai group， the high-dose Zhimu-Huangbai group exhibited a significant increase in the uterine index and BMD， and a significant reduction in body mass and PPARγ and Chemerin mRNA expression （P＜0.05 or P＜0.01）. Compared to high-dose Zhimu-Huangbai group， the estradiol group showed a decrease in uterine index， BV/TV， Tb.N， Tb.Th， BMD， and BMP-2 mRNA expression， while the levels of IL-1β， TNF-α， and IL-6， as well as Tb.Sp and the mRNA expressions of PPARγ， chemerin， and CMKLR1 increased （P＜0.05 or P＜0.01）. ConclusionThe Zhimu-Huangbai medicinal pair can alleviate PMOP bone loss， and its mechanism of action is related to reducing the levels of inflammatory factors， correcting the disorder of osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells （BMSCs）， and promoting the differentiation of BMSCs into osteoblasts.

To analyze the clinical characteristics of acute diquat poisoning complicated by central nervous system injury (CNSI) and identify early risk factors, aiming to provide a theoretical basis for reducing mortality in diquat poisoning with CNSI.

Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

Objective:To explore the impact of treatment duration with human urinary kallidinogenase (HUK) on the efficacy and safety of acute ischemic stroke (AIS).Methods:In this subgroup analysis of RESK study, a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group (HUK for 8 days, n=185) or long medication group (HUK for 15 days or 21 days, n=805). The proportions of patients with modified Rankin Scale (mRS) score of 0, 0-1, 0-2 at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 22 days, the proportions of patients with Barthel index (BI)≥95 at 90 days, and the incidences of adverse events were analyzed. Comparisons between groups were conducted using chi-square test, single factor and multivariate Logistic regression analysis, etc. Results:Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2 [74.1% (137/185) vs 75.0% (604/805); OR=1.047, 95% CI 0.676-1.620, P=0.838] and 22-day NIHSS score change from baseline (4.60±2.00 vs 4.26±2.80; OR=-0.390, 95% CI -1.125-0.344, P=0.297) showed no statistically significant difference between the short medication and long medication groups; the proportions of patients with 90-day mRS score of 0-1 [48.1% (89/185) vs 59.1% (476/805); OR=0.674, 95%CI 0.463-0.983, P=0.041] and 90-day BI≥95 [43.6% (79/181) vs 55.1% (442/802); OR=0.614, 95%CI 0.420-0.897, P=0.012] were significantly lower in the short medication group than in the long medication group. There was no statistically significant difference in the incidences of adverse events between these 2 groups. Conclusions:In AIS patients, consecutive 8-day dosing of HUK improved immediate (22-day NIHSS score) and long-term outcome (90-day mRS score 0-2) and was safely tolerated. When applicable, extended duration of HUK could improve long-term disability-free rate (90-day mRS score 0-1) and quality of life (90-day BI) without increasing the risk of adverse events.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
Humans ; Bone Remodeling ; Cell Differentiation ; Osteogenesis ; Semaphorin-3A/pharmacology* ; Trigeminal Ganglion/metabolism*