OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules （WYJYG） via the NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/apoptosis-associated speck-like protein containing a CARD （ASC）/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group， model group， MCC950 （NLRP3 inflammasome inhibitor） group （10 mg/kg）， fluoxetine group （positive control，2.08 mg/kg），low-dose WYJYG（3.78 g/kg） and high-dose WYJYG group （7.56 g/kg），with 10 rats in each group. From the 22nd day of the experiment， rats in the fluoxetine group， low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration， the contents of ASC， ionized calcium binding adaptor molecule 1 （Iba1）， interleukin-1β （IL-1β）， and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3， cluster of differentiation 68 （CD68）， Caspase-1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein were determined， and neuronal apoptosis was observed. RESULTS After the last administration， compared with the model group， the open-field activity time was significantly prolonged （ P ＜0.05）， and the latency to feed in a novel environment was significantly shortened （ P ＜0.05） in rats of the high-dose WYJYG group. In hippocampal tissue， the contents of ASC， Iba1， IL-1β， and IL-18， as well as the protein expression levels of NLRP3， Caspase-1， and CD68， and the positive rate of neuronal apoptosis were all significantly decreased/downregulated （ P ＜0.05）. Bcl-2 protein expression was significantly upregulated （ P ＜0.05）， and the density of neuronal apoptosis-positive cells was significantly reduced （ P ＜0.05）. CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway， reducing microglia-mediated neuroinflammation， and inhibiting hippocampal neurons apoptosis.

Skeletal muscle atrophy refers to a pathological condition characterized by muscle fiber atrophy as well as decreased muscle mass and muscle strength induced by various predisposing factors. It falls under the category of “flaccidity syndrome” in traditional Chinese medicine， and its pathogenesis is mainly associated with disturbed protein homeostasis， mitochondrial dysfunction and oxidative stress injury. Active ingredients of traditional Chinese medicine exerts synergistic regulatory effects via multiple pathways， thus possessing unique advantages in the clinical prevention and treatment of skeletal muscle atrophy. This paper reviews the mechanisms by which active ingredients of traditional Chinese medicine alleviate skeletal muscle atrophy. Existing studies have demonstrated that such active ingredients can ameliorate skeletal muscle atrophy through multiple approaches： regulating protein metabolic balance （geniposide， matrine， schisandrin A， etc.） and oxidative stress （astragaloside Ⅳ， Gastrodia elata polysaccharide， Angelica sinensis polysaccharide， etc.）， improving mitochondrial function （parthenolide， berberine， curcumin， etc.）， facilitating myogenesis and myogenic differentiation （cucurbitacin Ⅱb， saikosaponin A， saikosaponin D， etc.）， suppressing inflammatory response （ursolic acid， triptolide， emodin， etc.）， ameliorating insulin resistance （akebiasaponin D， etc.）. In the future， active ingredients of traditional Chinese medicine are expected to achieve breakthroughs in clinical treatment for skeletal muscle atrophy， providing novel ideas and strategies for the prevention and treatment of degenerative disorders.

ObjectiveTo improve the quality of artificial cultivation of the source plant of Fritillariae Cirrhosae Bulbus （FCB）， an XGBoost regression model was constructed based on the Group-Lasso method to screen the characteristic variables. The key factors affecting the quality formation of the source plant were then analyzed. MethodsFirstly， with the total alkaloid content （TAC） of FCB as the dependent variable， explanatory characteristic variables were screened from the influencing factors of TAC in the literature studying FCB quality from 2010 to 2024 based on the Group-Lasso regression algorithm. The screening results were verified by ten-fold cross-validation. Secondly， the present study established an XGBoost regression model to analyze the influencing factors of the quality formation of the source plant， and calculated the importance score of the explanatory characteristic variables. ResultsGroup-Lasso regression removed 2 numerical independent variables and retained the remaining 5 categorical variables and 6 numerical variables； cross-validation also showed that the number of screening variables is 11， with the corresponding optimal λ parameter value of 0.000 515 225 1. The results of XGBoost regression model confirmed the geographical origin as the most critical factor affecting the quality formation of source plants， followed by growth status and soil type， and then by mean temperature of the warmest month， original plant type， mean annual temperature， and altitude. Climate type， precipitation， frost-free period and relative humidity of the geographical origin exerted little effect. ConclusionThe prediction tools of Group-Lasso and XGBoost regression analysis models were preliminarily established for the quality formation of FCB. These models overcame the multicollinearity among numerical independent variables， and explored the geographical distribution of TAC and its key driving factors. The suitable cultivation areas can be selected or wild-tending bases established based on these key factors， thereby effectively avoiding blind introduction and cultivation. Finally， the present study provided a reference for the development and utilization of FCB， a theoretical basis for the market expansion and quality regulation， and a direction for the sustainable development and protection of new and efficient FCB resources.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective To investigate the effect of tissue-resident memory T cells(TRM)on imiquimod-induced psoriatic-like skin lesions in mice,and to elucidate the underlying mechanisms of TRM involvement in this process.Methods Forty female BALB/c mice were procured and randomly allocated into four groups:ten in the blank control group,and thirty for the establishment of a psoriasis mouse model.Following successful modeling,the thirty mice were further randomized into three groups:the model control group,the methotrexate-treated group,and the imiquimod-treated group,with ten mice in each group.Mice in the blank control group and model control group were uniformly treated with Vaseline for intervention.The methotrexate group and the imiquimod group were treated with 62.5mg of 5％imiquimod cream.The methotrexate group was administered by gavage at a dose of 1 mg/kg,and the gavage volume of each group was 10 mL/kg.The model control group,blank group and imiquimod group were gavaged with the same volume of normal saline.Treatment was conducted over six consecutive days.Subsequently,comparisons were made across groups regarding the psoriasis area and severity index(PASI),histopathological findings,inflammatory cytokine levels,and TRM cell levels.Results(1)The imiquimod group exhibited signifi-cantly lower scores for erythema(2.54±0.32),skin thickening(2.59±0.25),and scaling(2.52±0.29)compared to the methotrexate group,model control group,and blank control group(P<0.05).Additionally,the methotrexate group demonstrated reduced scores for erythema,skin thickening,and scaling compared to the model control group(P<0.05).(2)Hematoxylin-eosin(HE)staining revealed that the epidermis in the methotrexate group became thin-ner,with fewer parakeratotic cells and increased hair follicles.Conversely,the imiquimod group displayed abnor-mal cell morphology and relatively thicker white skin after modeling.(3)The imiquimod group showed significantly lower levels of TNF-α(51.63±4.39 pg/mL),IL-1β(35.53±4.15 pg/mL),IFN-γ(23.43±3.41 pg/mL),and IL-23(15.24±2.95 pg/mL)compared to the methotrexate and model control groups(P<0.05).Similarly,the methotrexate group exhibited reduced levels of TNF-α,IL-1β,IFN-γ,and IL-23 compared to the model control group(P<0.05).(4)The imiquimod group had significantly lower levels of CD8+CD103+cells(15.39±2.31)than the methotrexate and model control groups(P<0.05).Furthermore,the methotrexate group demonstrated lower levels of CD8+CD103+cells compared to the model control group(P<0.05).Conclusion Miquimod induces heavier skin lesions,faster response,and more epidermal thickening in psoriasis like mice.CD8+CD103+TRM cells and inflammatory factors may be involved in the recurrence of psoriasis.

Background:Acute pancreatitis(AP)is a common clinical gastrointestinal emergency with a high mortality rate.Intestinal dysfunction is one of the common complications of AP and can aggravate the disease condition.Therefore,early and accurate assessment of the disease severity and intestinal dysfunction of AP is of great significance for improving the prognosis of patients.Aims:To investigate the correlation of early serum levels of interleukin-1β(IL-1β),C-reactive protein(CRP),endotoxin(ET),D-lactic acid(D-LA),and diamine oxidase(DAO)with disease severity and intestinal dysfunction in AP patients.Methods:A total of 52 AP patients admitted to the Second Affiliated Hospital of Baotou Medical College from September 2023 to September 2024 were enrolled,and 10 healthy individuals recruited during the same period were served as the control group.AP patients were classified into mild acute pancreatitis(MAP),moderately severe acute pancreatitis(MSAP)and severe acute pancreatitis(SAP)groups according to the severity of the disease.Intestinal function was evaluated using the acute gastrointestinal injury(AGI)grading system.ELISA was used to detect the early serum levels of IL-1β,CRP,ET,D-LA,and DAO,and the correlation of these indicators with the severity of AP and AGI grade were analyzed by Spearman correlation coefficient.Results:Serum levels of IL-1β,CRP,ET,D-LA,and DAO in the MAP,MSAP,and SAP groups were significantly higher than those in the control group(all P<0.05);serum levels of IL-1β,CRP,ET,D-LA,and DAO in the MSAP group were significantly higher than those in the MAP group(all P<0.05);serum levels of IL-1β,CRP,ET,D-LA,and DAO in the SAP group were significantly higher than those in the MAP and MSAP groups(all P<0.05).Compared with AGI grade 0-Ⅰ subjects,serum levels of IL-1β,CRP,ET,D-LA,and DAO in patients with AGI grade Ⅱ,Ⅲ and Ⅳ were significantly increased(all P<0.05).Compared with AGI grade Ⅱ patients,serum D-LA level in patients with AGI grade Ⅲ was significantly increased(P<0.05).Compared with AGI grade Ⅲ patients,serum D-LA level in patients with AGI grade Ⅳ was significantly increased(P<0.05).Serum levels of IL-1β,CRP,ET,D-LA,and DAO were positively correlated with the severity of AP and AGI grade(all P<0.05).Conclusions:Early serum levels of IL-1β,CRP,ET,D-LA,and DAO in AP patients are significantly increased and closely related to the disease severity and intestinal dysfunction.

Objective:To evaluate the long-term efficacy and safety of recombinant coagulation factor Ⅷ (Octocog alfa) in Chinese patients with hemophilia A (HA) enrolled in the International Antihemophilic Factor Hemophilia A Outcome Database (AHEAD) study (NCT02078427) .Methods:Enrollment of Chinese patients in the AHEAD study was completed by January 2021, and data were collected up to July 15, 2022. This study primarily assessed patients in terms of the Gilbert score, global gait score within the Hemophilia Joint Health Score (HJHS), annualized bleeding rate (ABR), annualized joint bleeding rate, and adverse events.Results:A total of 168 male patients were included in this study, of which 113 received prophylactic treatment and 53 received on-demand treatment. The average age of the patients was 21.4±13.37 years. Compared with baseline, the global gait score within HJHS significantly decreased during the 1-year follow-up in patients with moderately severe HA in the prophylactic treatment group ( P=0.01) and on-demand treatment group ( P=0.008). The mean reduction in Gilbert score was greater in the prophylactic treatment group than in the on-demand treatment group (28.6% vs 8.2%). The average ABR decreased significantly during the 1-year follow-up (3.70 vs 7.78, P=0.01) in the prophylactic treatment group, particularly in patients with severe HA (2.14 vs 8.98, P=0.006) and pediatric patients (2.1 vs 4.73, P=0.03). The ABR score also decreased significantly in the moderate-dose prophylactic treatment group ( P=0.015). During the 1-year follow-up, 25 patients (14.9%) reported 39 adverse events, with only one patient developing treatment-related F Ⅷ inhibitor. Conclusion:Joint mobility improved in patients receiving either prophylactic or on-demand Octocog alfa. Bleeding episodes significantly reduced in patients receiving prophylactic treatment, particularly in pediatric patients and those with severe HA.

With the intensification of population aging, type 2 diabetes has emerged as a significant global public health concern, particularly in developing countries.Epidemiological data indicate that the elderly population faces a higher risk of diabetes, accompanied by an increasing incidence rate.Due to the unique pathological characteristics and comorbid chronic diseases prevalent among elderly diabetes patients, polypharmacy is both common and often unavoidable.Inappropriate polypharmacy poses heightened health risks for patients and complicates clinical management, underscoring the urgent need to optimize intervention strategies.Effective approaches include regular medication reviews, adjustments to blood glucose control targets, and the development of personalized deprescribing plans informed by comprehensive geriatric assessments.While some interventions have demonstrated positive effects in reducing potentially inappropriate medications, addressing prescription omissions, and enhancing medication adherence, their capacity to yield significant clinical improvements requires further validation.Future research should prioritize the identification of the most effective interventions for high-risk populations.

Objective:To report the clinical, electrophysiological, and genetic mutation characteristics of a family with paramyotonia congenita, to enhance clinical understanding of ion channelopathies, provide better guidance for clinical diagnosis, and optimize treatment plans.Methods:The clinical data, nerve conduction studies, needle electromyography, long exercise test, short exercise test, and whole-exome sequencing results of the proband with paramyotonia congenita and his family members admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, in August 2023 were collected and analyzed.Results:The proband was a 15-year-old male who presented with episodic muscle weakness for 1 year, accompanied by elevated creatine kinase during episodes. Between the ages of 3 and 4, he exhibited facial and bilateral hand myotonia triggered by cold exposure. His mother, sister, maternal grandmother, maternal aunt and uncle also displayed similar cold-induced facial and hand myotonia during childhood. Additionally, his cousin exhibited walking difficulties, frequent falls, mild difficulty in opening eyes after closure, and mild chewing and swallowing difficulties at the age of 1. Electromyography of the proband showed widespread myotonic discharges and myopathic impairment, while the electromyography of his mother and sister revealed only widespread myotonic discharges. The proband′s long exercise test results were consistent with periodic paralysis, while the short exercise test results aligned with paramyotonia congenita. His sister′s long exercise test results were within normal range, while the short exercise test results of his mother and sister were consistent with paramyotonia congenita. Genetic testing of the family revealed that all tested patients carried a heterozygous SCN4A mutation, c.4343G>A (R1448H). Conclusions:The R1448H mutation in the SCN4A gene is the genetic cause of this family. Patients carrying the SCN4A R1448H mutation may exhibit clinical features of cold-induced myotonia with or without episodic muscle weakness. In addition to widespread myotonic discharges on electromyography, certain patients may also show myopathic impairment. The long and short exercise tests can further assist in differentiating various types of myotonia and periodic paralysis for clinical diagnosis.

Surgical robot(SR),which integrates mechanical control,multimodal image navigation and artificial intelligence(AI)algorithms,is reshaping modern surgical paradigm with its advantages of minimally invasive operation,high precision and intelligent capabilities.The evolution,classification and representative commercial platforms of SR both domestically and internationally were systematically reviewed in this article,mainly focused on in-depth comparison of core parameters and key technological breakthroughs across different manufacturers and future development trends toward semi-autonomous and fully autonomous surgical systems.