Multimorbidity has emerged as a critical global public health challenge, necessitating effective management strategies. In Heilongjiang Province, a cold north region in China with a high prevalence of multimorbidity, healthcare disparities, uneven resource distribution, and inadequate chronic disease control remain pressing issues. Driven by national policies on family physician contracting and regional demands for chronic disease management, this study established a "hospital-community general practitioner co-management" model utilizing a mobile-based digital platform. This model integrates hospital-based general practitioners into primary care teams to optimize resource allocation and enhance multimorbidity management. The initiative aims to explore pathways for improving healthcare system reform and strengthening the chronic disease prevention framework in the region.

Multimorbidity has emerged as a critical global public health challenge, necessitating effective management strategies. In Heilongjiang Province, a cold north region in China with a high prevalence of multimorbidity, healthcare disparities, uneven resource distribution, and inadequate chronic disease control remain pressing issues. Driven by national policies on family physician contracting and regional demands for chronic disease management, this study established a "hospital-community general practitioner co-management" model utilizing a mobile-based digital platform. This model integrates hospital-based general practitioners into primary care teams to optimize resource allocation and enhance multimorbidity management. The initiative aims to explore pathways for improving healthcare system reform and strengthening the chronic disease prevention framework in the region.

Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.

Objective To evaluate the potential of serum exosomal miR-148a-5p as a biomarker and to investigate its role in the pathogenesis of rheumatoid arthritis(RA).Methods A total of 80 participants(30 healthy controls,HCs;50 RA patients)were recruited.Serum exosomes were extracted and identified.The expressions of exsomal miR-148a-5p will be screened by next-generation sequencing,validated by qRT-PCR and assessed its clinical significance.Target genes and their functions were determined by the luciferase reporter assays,cell transfection,and ELISA.Results Fifty-five differentially expressed serum exomiRNAs were identified(44 upregulated,11 downregulated).The high expression of the exo-miR-148a-5p in the serum of patients with RA was validated by qRT-PCR,comparing to HCs(P<0.000 1),which showed a strong correlation with the disease activity score(DAS)28,rheumatoid factor(RF),and erythrocyte sedimentation rate(ESR)and exhibited higher sensitivity and specificity of diagnostic(AUC 0.8633,95%CI 0.77～0.95).CREB5 was the potential target gene of miR-148a-5p.CCK-8 assays showed that miR-148a-5p mimic significantly promoted proliferation of MH7A and M0 macrophages at 48 h and 72 h(P<0.005).The miR-148a-5p inhibitor inhibited proliferation of MH7A and M0 macrophage at 48 h slightly(P<0.05),and better effects shown at 72 h(P<0.001).Additionally,miR-148a-5p mimic significantly reduced CREB5 protein expression in MH7A cells and increased the levels of MMP3 and CXCL10 in culture supernatant(P<0.001),which could be reversed by miR-148a-5p inhibitor.However,miR-148a-5p had no impact on protein expression of RBMXL1 or CREB5 in M0 macrophages.Conclusion Serum exosomal miR-148a-5p is a diagnostic marker and involves in the pathogenesis of RA,which promotes MH7A cell proliferation by affecting protein levels of CREB5 and excessive secretion of MMP-3,CXCL10.

Objective To evaluate the potential of serum exosomal miR-148a-5p as a biomarker and to investigate its role in the pathogenesis of rheumatoid arthritis(RA).Methods A total of 80 participants(30 healthy controls,HCs;50 RA patients)were recruited.Serum exosomes were extracted and identified.The expressions of exsomal miR-148a-5p will be screened by next-generation sequencing,validated by qRT-PCR and assessed its clinical significance.Target genes and their functions were determined by the luciferase reporter assays,cell transfection,and ELISA.Results Fifty-five differentially expressed serum exomiRNAs were identified(44 upregulated,11 downregulated).The high expression of the exo-miR-148a-5p in the serum of patients with RA was validated by qRT-PCR,comparing to HCs(P<0.000 1),which showed a strong correlation with the disease activity score(DAS)28,rheumatoid factor(RF),and erythrocyte sedimentation rate(ESR)and exhibited higher sensitivity and specificity of diagnostic(AUC 0.8633,95%CI 0.77～0.95).CREB5 was the potential target gene of miR-148a-5p.CCK-8 assays showed that miR-148a-5p mimic significantly promoted proliferation of MH7A and M0 macrophages at 48 h and 72 h(P<0.005).The miR-148a-5p inhibitor inhibited proliferation of MH7A and M0 macrophage at 48 h slightly(P<0.05),and better effects shown at 72 h(P<0.001).Additionally,miR-148a-5p mimic significantly reduced CREB5 protein expression in MH7A cells and increased the levels of MMP3 and CXCL10 in culture supernatant(P<0.001),which could be reversed by miR-148a-5p inhibitor.However,miR-148a-5p had no impact on protein expression of RBMXL1 or CREB5 in M0 macrophages.Conclusion Serum exosomal miR-148a-5p is a diagnostic marker and involves in the pathogenesis of RA,which promotes MH7A cell proliferation by affecting protein levels of CREB5 and excessive secretion of MMP-3,CXCL10.

Objective To investigate the efficacy and safety of single-channel endoscopic nylon rope combined with hemostatic clip suture in the treatment of peptic ulcer and bleeding.Methods Patients in our hospital due to peptic ulcer bleeding and hospitalization emergency electronic endoscopy from January 1st,2001 to July 1st,2017 were enrolled in the study.They were treated the single-channel endoscopic nylon rope combined with hemostatic clip suture.The basic information,clinical data,surgical records combined and retrospective analysed.Results 16 patients were included in the study.Among all the patients,peptic ulcer was located in 6 cases of gastric angle,3 cases of gastric antrum,3 cases of gastric body,2 cases of duodenal bulb and stomach.Ulcer maximum 40 mm × 25 mm,an average of (23.0 ± 6.0) mm.All ulcer wounds in patients underwent single-channel endoscopic nylon rope combined with hemostatic clip pouch suture were completely closed,including 1 case of duodenal ulcer patients after bleeding,achieved hemostasis successfully when turned into our hospital intervention.The remaining 15 cases were no longer bleeding.1 cases of gastric antral and 1 cases of stomach were diagnosed as moderately differentiated adenocarcinoma and they received endoscopic resuscitation after successful elective surgery gastric antral cancer radical surgery.Conclusions Single channel endoscopic nylon rope combined with hemostatic clip sacking is a safe and effective method for the treatment of giant peptic ulcer and bleeding.It is worthy of clinical manifestation,especially for those with deep and perforated ulcer.

Objective To investigate the correlation between C-reactive protein (CRP) level at admission and severity and early outcome of acute ischemic stroke.Methods Inpatients with acute ischemic stroke were enrolled retrospectively.The demographic and clinical data were collected.The National Institutes of Health Stroke Scale (NIHSS) at admission was used to evaluate the neurologic deficits,≤8 was defined as a mild stroke and ＞ 8 was defined as a severe stroke.The modified Rankin scale was used to evaluate the outcomes at discharge,0-2 was defined as good outcome and ＞ 2 was defined as poor outcome.Multivariate logistic regression analysis was used to determine the independent influencing factors of severity and early outcome of acute ischemic stroke.Results A total of 120 patients with acute ischemic stroke were enrolled in the study.Their mean age was 63.35 ± 11.51 years,71 (59.17％) were males;81 had mild stroke (67.5％),39 (32.5％) had moderate to severe stroke;71 (59.17％) had good outcome,and 49 (40.83％) had poor outcome.There were significant differences in the age,CRP level,and proportions of ischemic heart disease,atrial fibrillation,smoking,and drinking between the mild stroke group and the moderate to severe stroke group (all P ＜0.05).Multivariate logistic regression analysis showed that ischemic heart disease (odds ratio [OR] 4.407,95％ confidence interval [CI] 1.100-17.653;P=0.036),atrial fibrillation (OR 6.603,95％ CI 1.190-36.635;P =0.031) and CRP (OR 1.022,95％ CI 1.001-1.043;P =0.041)were independently and positively correlated with the severity of stroke.There were significant differences in baseline NIHSS score,fibrinogen and CRP level,as well as the proportions of the patients with atrial fibrillation,smoking,and drinking between the good outcome group and the poor outcome group (all P ＜0.05).Multivariate logistic regression analysis showed that smoking (OR 8.895,95％ CI 1.699-46.557;P=0.010),baseline NIHSS score (OR 2.241,95％ CI 1.567-3.206;P ＜0.001),and CRP (OR 1.195,95％ CI 1.030-1.386;P =0.019) were independently correlated with the early poor outcomes.Conclusion CRP level at admission was the independent influencing factor of severity and early outcome of acute ischemic stroke.