Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

AIM: To investigate the correlation between fundus blood flow parameters and carotid artery ultrasound blood flow parameters in patients with hypertensive retinopathy(HRP).METHODS: A total of 50 patients(22 left eyes and 28 right eyes)with HRP admitted to our hospital from June 2021 to June 2023 were retrospectively included as the experimental group, and 50 healthy physical examination subjects(22 left eyes and 28 right eyes)during the same period were included as the healthy group. Pearson correlation was used to analyze the correlation between fundus blood flow parameters and carotid artery ultrasound blood flow parameters.RESULTS: The AUC values of fundus blood flow parameters and carotid artery ultrasound blood flow parameters and their combined diagnosis of HRP were 0.853, 0.844 and 0.935, respectively. Pearson correlation analysis showed that carotid systolic peak blood flow velocity was negatively correlated with foveal avascular zone(FAZ)area, FAZ circumference and non-circularity index, and positively correlated with macular vascular density(all P<0.05). The end-diastolic blood flow velocity was positively correlated with FAZ area and macular vascular density(all P<0.05). The internal carotid artery resistance index was positively correlated with FAZ area(P<0.05).CONCLUSION: The combination of fundus blood flow parameters and carotid artery ultrasound blood flow parameters in the diagnosis of HRP has good application value in the diagnosis of HRP.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

Objective:To explore the influencing factors and implementation paths of medical and preventive integration of chronic disease in county medical communities (CMCs), providing references for further promoting the integration of medical and prevention and improving the collaborative mechanism of medical and prevention.Methods:From October to November 2023, based on the principle of geographically balanced sampling, medical staff from 6 leading hospitals and 18 other member units of 6 CMCs in Zhejiang Province were selected as survey subjects. A self-designed survey questionnaire was conducted, mainly including the development and evaluation of chronic disease medical and preventive integration services in CMCs. The service development was designed according to the collaborative symbiosis management model, including 4 dimensions of collaborative symbiosis scenarios, willingness, ability, and process, as well as 11 secondary elements. Using secondary elements as the conditional variables and the integration effect of chronic disease medical and prevention as the outcome variable, a qualitative comparative analysis method was used to explore the relationship between multiple conditional variables and their combinations with high integration effect of chronic disease medical and prevention.Results:571 valid questionnaires were collected, with an effective response rate of 96.62%. The consistency of a single secondary element(including conditional non sets) on the high effectiveness of medical and preventive integration was less than 0.9, which cannot constitute a necessary condition for explaining the outcome variable. The configuration analysis results showed that the consistency of the condition combination formed by the interaction of multiple secondary elements was 0.835-0.845, indicating that the condition combination of multiple elements constituted a sufficient non necessary condition for the high integration effect of chronic disease medical and prevention. The configuration path for achieving high integration of medical and preventive effects could be divided into four categories, among which the feature of scenario-process dominance was to create a perfect service scenario and service process as the main focus; The characteristic of the willingness-process dominant type was to stimulate the service willingness of medical staff and improve the service process as the leading factor; The characteristic of the scenario-willingness-ability dominant type was to create a comprehensive service scenario, stimulate the service willingness of medical staff, and enhance service capabilities as the main focus; The characteristic of the willingness-ability-process dominant type was to stimulate the service willingness of medical staff, enhance service capabilities, and improve the service process as the dominant factor. In addition, the four types of configuration paths mentioned above all covered the two secondary elements of endogenous dynamics and professional competence, with a total coverage of 0.626 and a total consistency of 0.821.Conclusions:The configuration path formed through the interaction of multiple elements can effectively achieve the integration of chronic disease medical and prevention. The CMCs should choose the appropriate configuration path based on the actual situation. In addition, special attention should be paid to the endogenous motivation and professional capacity building of medical staff.

Objective To prepare paclitaxel-natural borneol complex,and to explore the prescription and preparation process of paclitaxel-natural borneol complex drug-loaded submicroemulsion,and its in vitro anti-tumor effect.Methods The Paclitaxel-natural borneol complex was prepared by grinding method and identified by Fourier Transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC).The compound drug-loaded submicroemulsion was prepared using a two-step high-pressure emulsification method.The single-factor investigation and the orthogonal experimental design were applied to optimize the formulation and preparation process.MTT assay,cell cloning assay,and cell scratch assay were used to evaluate the effect of this preparation on HCT-116 cells.Results The infrared spectral absorption peaks of taxol-natural borneol complex at 3 312.76 cm-1 and 3 513.92 cm-1 disappeared,and DSC analysis showed that a new absorption peak of taxol-natural borneol complex appeared at 154.56 ℃,indicating that taxol be coupled with natural borneol to form a new complex.The optimal prescription was 0.44％active pharmaceutical ingredient[paclitaxel-natural borneol(1∶3)],10％medium chain triglyceride,3％emulsifier[egg yolk lecithin-Poloxam 188(1∶2)],2％glycerol,0.3％oleate.The optimal process was emulsification at 80 ℃,60 MPa high pressure homogenization 10 times.The half inhibitory concentration(IC50)was 0.75 μg·mL-1 by MTT asssy in cell.In the cell cloning assay,the scratch healing area of blank control group,paclitaxel raw material and paclitaxel/natural borneol submicroemulsion were(36.44±3.35)％,(13.59±9.28)％,(8.30±4.09)％,respectively.The results were statistically significant(P＜0.05).In the plate cloning experiment,the cell cloning rates of blank control group,paclitaxel bulk drug group and submicroemulsion group were(37.92±0.729)％,(9.16±1.335)％and(3.36±1.065)％,respectively,the differents were statistically significant(P＜0.05).Conclusion This submicroemulsion has reasonable prescription,feasible process and good stability.Cell experiments showed that the submicronemulision effectively inhibits the proliferation and migration of HCT-116 cells,suggesting its potential as a promising antitumor agent.

Background and Aims:There is currently no consensus on whether the pancreaticoduodenectomy with Heidelberg triangle operation(PDTRIANGLE)or the standard radical pancreaticoduodenectomy(PDSTANDARD)is more beneficial for patients with pancreatic cancer,and no large-scale multicenter studies have confirmed this.Therefore,this study was conducted to compare the clinical efficacy and safety of PDTRIANGLE and PDSTANDARD for treating pancreatic cancer through a Meta-analysis. Methods:Relevant literature comparing the two surgical approaches comparing the two surgical approaches for treating pancreatic cancer was screened from Chinese and English databases based on inclusion criteria.The search timeframe extended from the inception of the databases to May 2024,and Review Manager 5.3 software was used for Meta-analysis of the extracted outcome variables. Results:A total of 6 retrospective studies were included,comprising 658 patients,with 315 in the PDTRIANGLE group and 343 in the PDSTANDARD group.The Meta-analysis results showed that the operative time in the PDTRIANGLE group was longer than that in the PDSTANDARD group(OR=1.52,95％CI=0.42-2.61,P=0.007),the lymph node dissection rate was higher in the PDTRIANGLE group(OR=0.70,95％CI=-0.4-1.01,P＜0.000 01),and the R0 resection rate was also higher in the PDTRIANGLE group(OR=1.63,95％CI=1.03-2.58,P=0.04).The incidence rates of postoperative lymphatic fistula and diarrhea were higher in the PDTRIANGLE group compared to the PDSTANDARD group(OR=5.60,95％CI=1.81-17.29,P=0.003;OR=0.13,95％CI=0.07-0.20,P＜0.000 1).The length of hospital stay was longer in the PDTRIANGLE group(OR=0.40;95％CI=-0.14-0.65,P=0.003).The overall survival rates at 1 and 2 years were significantly better in the PDTRIANGLE group compared to the PDSTANDARD group(OR=2.19,95％CI=-1.27-3.76,P=0.005;OR=1.65,95％CI=-1.01-2.67,P=0.04),and the 1-year disease-free survival rate was also significantly higher in the PDTRIANGLE group(OR=3.71,95％CI=2.27-6.07,P＜0.000 01),although the difference in the 2-year disease-free survival rate between the two groups was not statistically significant(OR=2.63,95％CI=-0.91-7.59,P=0.07). Conclusion:PDTRIANGLE is a safe and effective treatment for pancreatic cancer.Compared to PDSTANDARD,PDTRIANGLE significantly improves the R0 resection rate,thereby enhancing the postoperative disease-free survival rate and achieving a better long-term prognosis.