ObjectiveTo examine the effects of Chaihu Jia Longgu Muli Tang （CLMT）-containing serum on Neuro-2A cell damage when exposed to conditioned medium from lipopolysaccharide （LPS）-stimulated microglia （BV-2） and explore the underlying mechanism. MethodsBV-2 cells were activated by LPS at a concentration of 1 mg·L^-1 to generate conditioned medium. Concurrently， a blank control group， a model group and groups treated with varying concentrations of CLMT （5%， 10%， and 15%）， dexamethasone （2.5 μmol·L^-1）， stimulator of interferon genes （STING） agonist （MSA-2， 10 μmol·L^-1）， and STING inhibitor （STING-IN-4， 4 μmol·L^-1） were established. Neuro-2A cells were subsequently cultured in the conditioned medium from each treatment group. The viability of BV-2 cells following interventions was assessed by the cell counting kit-8 （CCK-8） assay. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the supernatant of Neuro-2A cells from each group were measured through enzyme linked immunosorbent assay （ELISA）. Additionally， the expression of tyrosine hydroxylase （TH） in Neuro-2A cells was evaluated through immunohistochemistry （IHC）， while the expression of phosphorylated alpha-synuclein （p-α-Syn） was assessed by immunofluorescence （IF） assay. The expression levels of STING， interferon regulatory factor 3 （IRF3）， phosphorylated interferon regulatory factor 3 （p-IRF3）， nuclear transcription factor-kappa B p65 （NF-κB p65）， and phosphorylated nuclear transcription factor-kappa B p65 （p-NF-κB p65） in Neuro-2A cells were determined by Western blot. ResultsIn comparison to the control group， both the model group and the MSA-2 group exhibited reduced viability of Neuro-2A cells （P<0.01）， elevated concentrations of TNF-α， IL-1β， and IL-6 in the cell supernatant （P<0.01）， reduced expression of TH （P<0.01）， increased expression of p-α-Syn （P<0.01）， and upregulated relative protein levels of STING， p-IRF3， and p-NF-κB p65 （P<0.01）. Compared with the model group， medium- and high-dose CLMT enhanced the viability of Neuro-2A cells （P<0.01）， lowered the levels of TNF-α， IL-1β， and IL-6 （P<0.01）， promoted TH expression， and suppressed p-α-Syn expression （P<0.01）. In the dexamethasone group， the levels of IL-6， TNF-α， and IL-1β were reduced （P<0.05， P<0.01）. In the STING-IN-4 group， the levels of TNF-α and IL-1β were decreased （P<0.01）. The expression of TH was increased in both the dexamethasone group and the STING-IN-4 group （P<0.01）， while the expression of p-α-Syn was reduced （P<0.01）. The relative protein levels of p-IRF3， STING， and p-NF-κB p65 were reduced in medium- and high-dose CLMT groups （P<0.05， P<0.01）. Similarly， the dexamethasone group exhibited decreases in the expression levels of STING， p-IRF3， and p-NF-κB p65 （P<0.01）. In the STING-IN-4 group， the expression levels of p-NF-κB p65， STING， and p-IRF3 were also diminished （P<0.05， P<0.01）. However， no statistically significant differences were observed in the expression of IRF3 or NF-κB p65 across the groups. ConclusionCLMT has the potential to suppress the activation of BV-2 microglial cells， consequently mitigating the inflammatory response induced by LPS and further preventing inflammation-mediated damage to Neuro-2A cells. The underlying mechanism is likely associated with the modulation of the STING/NF-κB signaling pathway， which results in reduced inflammation and confers neuroprotective effects.

How to use family doctors as a starting point to improve the level of chronic disease management is still a ma-jor challenge in China.This study summarizes the current chronic disease management models,family doctor contract service models,and new digital health technologies in China.It expounds the connection between the three and explores the advantages of new digital health technologies in chronic disease management and family doctor contract services,aiming to provide a solid theoretical foundation for improving the level of chronic disease management.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

How to use family doctors as a starting point to improve the level of chronic disease management is still a ma-jor challenge in China.This study summarizes the current chronic disease management models,family doctor contract service models,and new digital health technologies in China.It expounds the connection between the three and explores the advantages of new digital health technologies in chronic disease management and family doctor contract services,aiming to provide a solid theoretical foundation for improving the level of chronic disease management.

Objective To investigate the possible mechanism of myocardial protective effect of Yixin formula in rats with myocardial ischemia-reperfusion injury.Methods Sixty-five rats were randomly divided into 10 in the sham-operated group and 55 in the modeling group;the modeling group was constructed by ligating the left anterior descending branch of the coronary artery,and the sham-operated group was only threaded without ligation.The modeling group was randomly divided into model group,Yixin formula low,medium and high dose group and trimetazidine group after membrane creation.The low,medium and high dose groups of Yixin formula were given 6.84 g·kg-1,13.68 g·kg-1 and 27.36 g·kg-1 of Yixin formula and 5.4 mg·kg-1 of Trimetazidine respectively,and the sham-operated group and the model group were given equal volume of saline by gavage for 7 days in each group.Echocardiography was used to detect the cardiac function of rats;biochemical methods were used to detect serum creatine kinase(CK),lactate dehydrogenase(LDH)and glutamate transaminase(AST);hematoxylin-eosin(HE)staining was used to observe the histopathological changes of rat myocardium;Masson staining was used to observe the degree of myocardial fibrosis;TUNEL staining for myocardial cell apoptosis index;Western blot was performed to detect NLRP3,pro-Caspase-1 and GSDMD-FL、GSDMD-N protein expression in myocardial tissue.Results Compared with the sham-operated group,the model rats showed significantly lower left ventricular ejection fraction(LVEF)and LV short-axis shortening percentage(FS)(P＜0.001),significantly higher myocardial injury markers CK,AST,and LDH(P＜0.001),pathological findings showed myocardial structural damage,interstitial edema with inflammatory cell infiltration,disorganized myocardial fiber arrangement,larger myocardial cell cross-sectional The pathological results showed that myocardial structure was damaged,interstitial edema with inflammatory cell infiltration,disorganized myocardial fiber arrangement,large cross-sectional area of myocardial cells(P＜0.001),significant myocardial collagen fibrosis(P＜0.001),the pyroptosis index of myocardial cells was increased(P＜0.001),and significantly increased NLRP3,pro-Caspase-1,GSDMD-FL,and GSDMD-N protein expression in myocardial tissues(P＜0.001).Compared with the model group,LVE and FS were significantly higher in each dose group of Yixin formula and trimetazidine group(P＜0.05,P＜0.001),myocardial injury markers CK,AST and LDH were significantly decreased(P＜0.05,P＜0.01,P＜0.001),myocardial cell cross-sectional area was reduced(P＜0.05,P＜0.001),myocardial fibrosis was reduced to different degrees(P＜0.001),the apoptosis index of cardiomyocytes was decreased(P＜0.05,P＜0.001),and NLRP3,pro-Caspase-1,and GSDMD protein expression in myocardial tissue was reduced(P＜0.001).Conclusion Yixin formula can reduce myocardial injury and the degree of myocardial fibrosis,and thus improve the cardiac function in rats.and its mechanism may be related to down regulating NLRP3/Caspase-1/GSDMD signaling pathway and inhibiting cardiomyocyte pyroptosis.

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.

Objective To establish an HPLC fingerprint of Dingdang Qigui Decoction and analyze and evaluate it using chemical pattern recognition technology;To determine the contents of 5 effective chemical components in Dingdang Qigui Decoction;To provide a basis for its quality control.Methods The analysis was performed on Agilent 5 TC-C18(2)column(250 mm×4.6 mm).The mobile phase comprised of acetonitrile-0.1%phosphoric acid aqueous solution with the gradient elution at a flow rate of 1.0 mL/min.The detection wavelength was set at 260 nm.The column temperature was maintained at 30℃and the injection volume was 10 μL.SPSS 26.0 and SIMCA 14.1 were used to perform clustering analysis and principal component analysis on the 10 batches of Didang Qigui Decoction.The landmark components for inter batch differences were selected through orthogonal partial least squares discriminant analysis(OPLS-DA).Results The HPLC fingerprint with eighteen common peaks of Didang Qigui Decoction in 10 batches of sample was established,and the similarities of samples were between 0.828 and 0.989.Five indicative components were identified and quantitatively analyzed by comparing with the reference substances,which were paeoniflorin,mauroisoflavone glucoside,hesperidin,cinnamaldehyde and aloe rhodopsin.The linear ranges was 10.000 0-320.000 0 μg/mL,2.500 0-80.000 0 μg/mL,10.000 0-320.000 0 μg/mL,10.000 0-320.000 0 μg/mL,0.078 1-5.000 0 μg/mL,respectively,and their mean recovery ranged from 100.30%to 104.09%.Clustering analysis and principal component analysis divided 10 batches of samples from Didang Qigui Decoction into 2 categories.Through OPLS-DA screening,hairy pistil isoflavone glycosides,paeoniflorin,and hesperidin were selected as landmark components for quality differences.Conclusion The quality evaluation method for Didang Qigui Decoction established in this study is simple,sensitive,accurate,and reproducible,which can provide a basis for the quality evaluation of Didang Qigui Decoction.

As an essential trace element in organisms,Zn2+is involved in the formation of protein structure and as a coenzyme factor affects cell homeostasis.The imbalance of Zn2+homeostasis is closely related to the occurrence and metastasis of pancreatic cancer.Zn2+homeostasis is regulated by two zinc transporter families,ZIP and ZnT,which mediate the processes of cell proliferation,differentiation and death.The ZIP protein family is mainly involved in DNA damage repair,cellular immunity,exosome secretion,and epithelial-mesenchymal transition(EMT)processes through RAS/RREB1 and cAMP/JAK/STAT signaling pathways,thereby affecting pancreatic cancer.The ZnT protein family mainly promotes the occurrence and development of pancreatic cancer through ERK,p38MAPK,NF-κB,and mTOR pathways.This review aims to provide some theoretical basis for the prevention,diagnosis,treatment and prognosis of pancreatic cancer.

Objective To investigate the factors influencing the prognosis of complex intracranial aneurysms treated with pipeline flow-directed device(PED)and to develop a nomogram prediction model.Methods The clinical data of a total of 98 patients with complex intracranial aneurysm,who were admitted to the Anyue County People's Hospital or the Second Affiliated Hospital of Guilin Medical College of China from January 2021 to April 2023 to receive PED treatment,were retrospectively analyzed.The influencing factors that might affect the prognosis of patients with complex intracranial aneurysm were collected.According to the modified Rankin Scale(mRS)score,the patients were divided into good prognosis group(being defined as mRS ≤2 points)and poor prognosis group(being defined as mRS＞2 points).The clinical data were compared between the two groups,and a nomogram model was established and validated.Results In the 98 patients,poor prognosis was seen in 10(10.20％).The differences in age,history of hypertension,history of diabetes mellitus,clopidogrel resistance,Fisher classification,repeated aneurysm rupture,aneurysm location,aneurysm size,aneurysm neck,multiple lesions,and Hunt-Hess grade on admission between good prognosis group and poor prognosis group were statistically significant(all P＜0.05).Multivariate analysis revealed that history of hypertension,clopidogrel resistance,repeated aneurysm rupture,aneurysm location,multiple lesions,and Hunt-Hess grade were the independent factors influencing the prognosis of patients with complex intracranial aneurysm after receiving PED treatment.The AUC of the nomogram model in predicting the prognosis of PED for complex intracranial aneurysms was 0.849(95％CI=0.758-0.939).The predicted curves of the model group and validation group were basically fitted to the standard curves.The results of the decision curve analysis showed that the net benefit to patients was greater than 0 when the probability threshold of the nomogram model for predicting a poor prognosis of PED for complex intracranial aneurysms was 0.10-0.90.Conclusion The factors causing poor prognosis of PED for complex intracranial aneurysms mainly include history of hypertension,clopidogrel resistance,repeated aneurysm rupture,etc.The nomogram model established in this study can predict the risk of poor prognosis in patients with complicated intracranial aneurysm after receiving PED treatment.

To explore the method of constructing the first-class undergraduate course of Treatise on Febrile Diseases. The undergraduates majoring in traditional Chinese medicine were selected as the teaching subjects. Three combinations (combination of theory and clinics, combination of science and education, and combination of ideological/political education and professional education) were adopted as the starting point. A variety of teaching methods were used. The combination of in-class and after-class and the combination of theory and clinics were implemented. Course construction was carried out from the aspects of course objectives, course resource construction, course content, organization and implementation, and course evaluation methods. Emphasis was placed on the process evaluation and formative evaluation. Questionnaire survey and final examination were used to evaluate the teaching effect. The results showed that a total of 10 first and second prizes were awarded in the provincial and municipal innovation competitions related to the theory of cold disease in the past three years. During the same time, more than 70 medical records were collected and collated, 82 research papers and 155 learning experiences were documented, five communities were visited along with the affiliated hospital and the school hospital for providing healthcare services in rural areas, and more than 20 traditional Chinese diagnosis and treatment activities were performed in these communities. The average score of students in overall course evaluation was 87. More than 94.00% (141/150) students highly evaluated the course construction. They believed that the course construction was very helpful to the theoretical study and clinical application of Treatise on Febrile Diseases, and improved their levels and abilities in classic reading, medical case evaluation and analysis, and syndrome differentiation and treatment. Students' recognition of this course has been improved and phased results have been achieved.