Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective To evaluate the relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM)based on imaging and clinical testing data.Methods Totally 600 T2DM patients who visited the First People's Hospital of Ziyang from March 2021 to December 2022 were included.The fundus photography and fundus fluorescein angiography were performed on all these patients and their age,gender,T2DM duration,cardiovascular diseases,cerebrovascular disease,hypertension,smoking history,drinking history,body mass in-dex,systolic blood pressure,diastolic blood pressure and other clinical data were collected.The levels of fasting blood glu-cose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c),24 h urinary albumin(UAlb),urinary albumin to creati-nine ratio(ACR),serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Logistic regression was used to analyze the risk factors associated with DR.DR staging was performed according to fundus images,and the convolutional neural network(CNN)algorithm was used as an image analysis method to explore the correlation between DR and DN based on emission computed tomography(ECT)and clinical testing data.Results The average lesion area rates of DR and DN detected by the CNN in the non-DR,mild-non-proliferative DR(NPDR),moderate-NPDR,severe-NPDR and pro-liferative DR(PDR)groups were higher than those obtained by the traditional algorithm(TCM).As DR worsened,the Scr,BUN,24 h UAlb and ACR gradually increased.Besides,the incidence of DN in the non-DR,mild-NPDR,moderate-NPDR,severe-NPDR and PDR groups was 1.67％,8.83％,16.16％,22.16％and 30.83％,respectively.Logistic regression analysis showed that the duration of T2DM,smoking history,HbA1c,TC,TG,HDL-C,LDL-C,24 h UAlb,Scr,BUN,ACR and glomerular filtration rate(GFR)were independent risk factors for DR.Renal dynamic ECT analysis demonstrated that with the aggravation of DR,renal blood flow perfusion gradually decreased,resulting in diminished renal filtration.Conclusion The application of CCN in the early stage DR and DN image analysis of T2DM patients will improve the diag-nosis accuracy of DR and DN lesion area.The DN is worsening as the aggravation of DR.

Objective: To find out the differences in gene characteristics between cervical cancer patients with and without lymph node metastasis, and to provide reference for therapy. Methods: From January 2018 to June 2022, recurrent cervical cancer patients 39 cases with lymph node metastasis and 73 cases without lymph node metastasis underwent testing of 1,021 cancer-related genes by next-generation sequencing. Maftools software was used to analyze somatic single nucleotide/insertion-deletion variation mutation, co-occurring mutation, cosmic mutation characteristics, oncogenic signaling pathways. Results: EP300 and FBXW7 were significantly enriched in lymph node-positive patients.Lymph node-positive patients with EP300 or FBXW7 mutations had lower overall survival (OS) after recurrence. Both lymph node-positive and -negative patients had plenty of co-occurring mutations but few mutually exclusive mutations. Lymph node-positive cooccurring mutation number ≥6 had lower OS, while lymph node-negative co-occurring mutation number ≥3 had lower OS after recurrence. The etiology of SBS3 was defects in DNA double strand break repair by homologous recombination, which exclusively exist in lymph node-positive patients. There was no difference in median tumor mutation burden (TMB) between positive and negative lymph nodes, but TMB was significantly associated with PIK3CA mutation. Conclusion The somatic SNV/Indels of EP300 and FBXW7, SBS3 homologous recombination-mediated DNA repair defect were enriched in lymph node-positive patients.For lymph node-positive patients, EP300 or FBXW7 mutations predicted poor prognosis. No matter lymph node-positive or negative, more co-occurring mutation number predicted poor prognosis. PIK3CA mutation may account for the higher TMB and help identify patients who benefit from immunotherapy.

Objective: To find out the differences in gene characteristics between cervical cancer patients with and without lymph node metastasis, and to provide reference for therapy. Methods: From January 2018 to June 2022, recurrent cervical cancer patients 39 cases with lymph node metastasis and 73 cases without lymph node metastasis underwent testing of 1,021 cancer-related genes by next-generation sequencing. Maftools software was used to analyze somatic single nucleotide/insertion-deletion variation mutation, co-occurring mutation, cosmic mutation characteristics, oncogenic signaling pathways. Results: EP300 and FBXW7 were significantly enriched in lymph node-positive patients.Lymph node-positive patients with EP300 or FBXW7 mutations had lower overall survival (OS) after recurrence. Both lymph node-positive and -negative patients had plenty of co-occurring mutations but few mutually exclusive mutations. Lymph node-positive cooccurring mutation number ≥6 had lower OS, while lymph node-negative co-occurring mutation number ≥3 had lower OS after recurrence. The etiology of SBS3 was defects in DNA double strand break repair by homologous recombination, which exclusively exist in lymph node-positive patients. There was no difference in median tumor mutation burden (TMB) between positive and negative lymph nodes, but TMB was significantly associated with PIK3CA mutation. Conclusion The somatic SNV/Indels of EP300 and FBXW7, SBS3 homologous recombination-mediated DNA repair defect were enriched in lymph node-positive patients.For lymph node-positive patients, EP300 or FBXW7 mutations predicted poor prognosis. No matter lymph node-positive or negative, more co-occurring mutation number predicted poor prognosis. PIK3CA mutation may account for the higher TMB and help identify patients who benefit from immunotherapy.

Objective: To find out the differences in gene characteristics between cervical cancer patients with and without lymph node metastasis, and to provide reference for therapy. Methods: From January 2018 to June 2022, recurrent cervical cancer patients 39 cases with lymph node metastasis and 73 cases without lymph node metastasis underwent testing of 1,021 cancer-related genes by next-generation sequencing. Maftools software was used to analyze somatic single nucleotide/insertion-deletion variation mutation, co-occurring mutation, cosmic mutation characteristics, oncogenic signaling pathways. Results: EP300 and FBXW7 were significantly enriched in lymph node-positive patients.Lymph node-positive patients with EP300 or FBXW7 mutations had lower overall survival (OS) after recurrence. Both lymph node-positive and -negative patients had plenty of co-occurring mutations but few mutually exclusive mutations. Lymph node-positive cooccurring mutation number ≥6 had lower OS, while lymph node-negative co-occurring mutation number ≥3 had lower OS after recurrence. The etiology of SBS3 was defects in DNA double strand break repair by homologous recombination, which exclusively exist in lymph node-positive patients. There was no difference in median tumor mutation burden (TMB) between positive and negative lymph nodes, but TMB was significantly associated with PIK3CA mutation. Conclusion The somatic SNV/Indels of EP300 and FBXW7, SBS3 homologous recombination-mediated DNA repair defect were enriched in lymph node-positive patients.For lymph node-positive patients, EP300 or FBXW7 mutations predicted poor prognosis. No matter lymph node-positive or negative, more co-occurring mutation number predicted poor prognosis. PIK3CA mutation may account for the higher TMB and help identify patients who benefit from immunotherapy.

Cerebral infarction, with high incidence, high mortality, high disability and high recurrence rates, can impose a serious burden on families and society. After cerebral infarction occurrence, neurons, as the fundamental structures of the central nervous system, are unable to renew or multiply after death; hence, full recovery from neurological impairments following cerebral infarction is challenging. With stem cell and genetic recombination advancements, cellular replacement therapy after cerebral infarction progresses, which helps clinical transformation and application. In this paper, the basic researches of cellular replacement therapy after cerebral infarction are reviewed from 3 aspects: endogenous nerve regeneration, exogenous stem cell transplantation, and in situ somatic cell trans-differentiation into neurons, in order to provide references for cerebral infarction treatment

One hundred and fifty diabetic patients,who received management by community family doctors and hospital consortium (1+1+1) team for at least 1 year,were enrolled from January 2017 to May 2017.After that they continued to receive the management for 1 more year by the team which were trained with TeamSTEPPS (team strategies and tools to enhance performance and patient safety).The management effect before and after TeamSTEPPS training was compared.After the TeamSTEPPS training,the team management ability was improved,so that the compliance of diabetic patients with medical advice,regular examination of blood glucose,regular follow-up assessment,health education,regular exercise and diet control were all better than before,and the differences were statistically significant (all P＜0.01).Fasting blood glucose,postprandial 2 h-blood glucose,glycosylated hemoglobin and LDL-C levels were all lower than before,and the achieved rate of the above indicators were also increased (P＜0.05).It is suggested that application of TeamSTEPPS in team training can effectively enhance the management ability for chronic disease of family doctors and improve compliance and clinical indicators of patients with diabetes under management.

Objective: Symptomatic intracranial hemorrhage (sICH) is one of the severe complications of ischemic stroke thrombolysis. Several prognostic scales have been developed to predict the risk of sICH. The performance of seven scales was compared in a single center cohort. Methods: Data of patients with consecutive ischemic stroke who received 0.9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis within 4.5 h time window from stroke onset were collected. Seven scales that can provide an estimate of risk of sICH were identified and evaluated: Hemorrhage After Thrombolysis (HAT), blood Sugar, Early infarct signs, (hyper) Dense cerebral artery sign, Age, National Institutes of Health (NIH) Stroke Scale (SEDAN), Stroke Prognostication using Age and NIH Stroke Scale (SPAN)-100, Safe Implementation of Thrombolysis in Stroke (SITS), Total Health Risks In Vascular Events (THRIVE), Glucose at presentation, Race (Asia), Age, Sex (male), systolic blood Pressure at presentation, and Severity of stroke at presentation (NIH Stroke Scale; GRASPS) and Multicenter Stroke Survey (MSS). The area under the receiver operating characteristic curve (AUROC) was calculated and Logistic regression and the Hosmer-Lemeshow test were also performed. Results: The current study included 293 patients, of whom 7.85% (23/293) had sICH by National Institute of Neurological Disorders and Stroke (SICH_NINDS), 5.46% (16/293) by Europe Cooperative Acute Stroke Study Ⅱ (SICH_ECASSⅡ) and 4.44% (13/293) by Safe Implementation of Thrombolysis in Stroke (SICH_SITS) criteria. SEDAN had the highest AUROC for predicting sICH: sICH_NINDS: AUROC=0.843, OR=3.167, 95%CI 2.106-4.762, P<0.01; sICH_ECASSⅡ: AUROC=0.797, OR=2.509, 95%CI 1.652-3.812, P<0.01; sICH_SITS: AUROC=0.784, OR=2.172, 95%CI 1.405-3.357, P<0.01. And SPAN-100 had the lowest AUROC among all the seven scales and was only associated with risk of SICH_NINDS in regression analysis. Furthermore, when sub-grouped the cohort into anterior circulation infarction and posterior circulation infarction, regression analysis suggested that all the seven scales were however not associated with sICH risk in patients with posterior circulation infarction. Conclusions SEDAN constantly had the highest predictive power, SPAN-100 had the worst. The seven scales studied could not predict sICH in posterior circulation infarction.

Objective To evaluate the application of TeamSTEPPS in training of community osteoporosis management team .Methods The TeamSTEPPS was applied for training of osteoporosis management team, and 1 513 residents aged ≥45 year were screened for osteoporosis in Kangjian community from January 2014 to March 2017.The identified patients with osteopenia and osteoporosis were intervened for one year.Cognitive level of the risk factors and symptoms associated with osteoporosis were assessed by questionnaires before and after the intervention .The bone density was examined at baseline and 6 months, 12 months after intervention.The effect of intervention was evaluated .Results A total of 467 patients (30.87%) with osteopenia and 476 patients (31.46%) with osteoporosis were detected .The cognitive levels of osteoporosis risk factors , including low calcium, vitamin D deficiency, lack of exercise, low weight, women menopause, matrilineal family history, smoking, excessive alcohol drinking and coffee drinking, were higher than those before intervention ( χ2＝62.909,78.742,59.974,50.478,29.512, 34.699,6.500,15.779,6.089,all P＜0.05).The awareness rates of symptoms , including lower back pain or body bone pain, shorter height and hunchback , low energy or nonviolent fracture , were also increased (χ2＝59.942,76.220,16.856,all P＜0.01).After intervention, the bone mineral density levels were increased compared to those before intervention (F＝530.28, P＜0.01 for osteopenia group; F＝339.51, P＜0.01 for osteoporosis group ); meanwhile, the differences were also significant between 6 months, 12 months after intervention and before intervention , between 12 months and 6 months after intervention (t＝-0.452,-0.968,-0.516,all P＜0.01 for osteopenia group; t＝-0.530,-1.045,-0.518, all P＜0.01 for osteoporosis group ).Conclusion The community osteoporosis management team trained by TeamSTEPPS can effectively improve the management levels of osteoporosis among residents in the community.

Objective Analyzes the condition of serum 25-hydroxy Vitamin D (25OHD)level of partial middle and old age physical examinations in Yinchuan area.Methods Tested the level of serum 25OHD of 1 520 cases of senile medical with electrochemiluminescence immunoassay (ECLIA)in October 2013 to September 2014 in Yinchuan,NingXia.exclusion of liv-er,kidney,cancer,diabetes and other diseases,and statistical analysis of each age group and one year 25-(OH)D distribution. Compared gender and 50~59,60~69,>70 years at different ages and spring,summer,autumn,winter four seasons 25OHD level distribution.Results All the mean level was 14.67±8.26 ng/ml.The lack and deficiency of Vitamin D account was 80.66%,and the female was 84.49% significantly higher than the male 74.96% (t=2.03,P<0.05).Used divide subjects into fore groups:the lack (42.76%),the deficiency (37.90%),nomal (13.68%)and good (5.66%)by the level of serum 25OHD.Vitamin D nutritional status was different in person of different ages.Fuither linear correlation analys showedgative correlation between the level of serum 25OHD and age (r=0.16,P<0.01).There was seasonal variation in the level of ser-um 25OHD (F=19.30,P<0.001).It was highest in summer,and lower in spring and winter.Conclusion Vitamin D of middle-aged and old people in Yinchuan was general deficiency,which should pay more attention and actively treatment to these patients.