Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To quantitatively evaluate the level of the three medical linkage in China from 2009 to 2022,explore the influencing factors and driving paths of the three medical linkage in China,and provide a new perspective for promoting the development of the three medical linkage.Methods:An optimized coupling coordination degree model was used to calculate the coupling coordination degree between the trinity healthcare systems and different binary systems within the systems in 31 provinces of China(excluding Hong Kong,Macao and Taiwan),and the Fuzzy-set Qualitative Comparative Analysis method was used to explore the condition configurations of multi-factor-driven three medical linkage.Results:From 2009 to 2022,the coupling coordination degree between the trinity healthcare systems in each province of China generally showed an increasing trend year by year.Among the binary systems,the overall coordinated development situation between the medical and medical insurance systems was the best and the regional development was the most balanced.The coupling coordination degree gap between the trinity healthcare system and the internal binary systems among provinces gradually widened,and the multi-polarization trend intensified.The paths to promote high-level three medical linkage can be summarized into two types:internal and external balanced development type(H1)and government-led type(H2,H3),among which the H1 path with per capita GDP and health expenditure as core conditions was the most common.Conclusion:It is suggested to enhance institutional and technological innovation,and integrate resources through a cross-departmental collaboration mechanism and digital technology.Provinces should select high-level optimization paths by leveraging regional endowments to narrow the regional development gap.Meanwhile,under the impetus of high-level policies,the protection and supervision system continues to improve,thereby promoting the three medical linkage.

Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

Water-soluble silver nanoclusters(DHLA-AgNCs)with red fluorescence emission were synthesized using silver nitrate(AgNO3)as silver source,dihydrolipoic acid(DHLA)as ligand and sodium borohydride(NaBH4)as reducing agent by one-pot method.Based on the selective quenching of DHLA-AgNCs by tetracycline(TC),a rapid and selective fluorescence analysis method for detection of TC was constructed by monitoring the fluorescence intensity change at 650 nm.Under the optimal detection conditions,the fluorescence quenching efficiency of DHLA-AgNCs showed good linear relationship with concentration of TC within the range of 10.0-120.0 μmol/L,and the limit of detection(LOD)was 0.39 μmol/L.This method was successfully applied to detection of TC in milk samples,with spiked recoveries ranging from 99.5%to 102.5%,and relative standard deviations(RSDs)less than 5%.This method had the advantages of simplicity,rapidity,strong specificity and low cost,and thus provided a simple and feasible strategy for selective detection of TC.

AIM To investigate effects of petroleum ether fraction from Derris eriocarpa How on glucose and lipid metabolism in a mouse model of metabolic syndrome(MS).METHODS KM mice were fed a high-fat diet and administered streptozotocin intraperitoneally to establish MS models.The MS mice were then randomly assigned to the model group,the metformin hydrochloride group,the lovastatin group,the ursolic acid group,and the high-,medium-and low-dose D.eriocarpa petroleum ether fraction groups,with 10 mice in each group.Ten additional mice maitained on a normal diet served as the normal control group.After 4 weeks of intragastric administration,glucose and lipid metabolism indicators were measured.Hepatic pathological changes were assessed using HE staining and oil red O staining.Liver tissue mRNA expressions of ATF3,PEPCK,FXR,CYP7A1,HNF4ɑ,CYP8B1 and SRB1 were quantified by RT-qPCR.Hepatic protein expressions of ATF3,HNF4ɑ,PEPCK,FXR and CYP7A1 was analyzed by Western blot in MS mice.RESULTS Compared to the model group,the high-dose D.eriocarpa petroleum ether fraction group exhibited significant glucose tolerance improvement(reduced OGTT-AUC,P＜0.01);favorable serum lipid modulation in terms of increased HDL-C levels(P＜0.01)and decreased TG,TC,LDL-C(P＜0.01);reduced renal biomarkers(BUN,SCR)and hepatotoxic indicators of TBA,AST and ALT activities(P＜0.01);alleviated hepatic lipid accumulation and histopathological damage;downregulated mRNA and protein expressions of ATF3,HNF4ɑ and PEPCK,as well as CYP8B1 mRNA expression(P＜0.01);and upregulated mRNA and protein expressions of FXR and CYP7A1,along with SRB1 mRNA expression(P＜0.01).CONCLUSION D.eriocarpa petroleum ether fraction ameliorates glucose and lipid metabolism dysregulation in MS mice by modulating the ATF3/HNF4ɑ/CYP7A1 signaling pathway,consequently eliciting hypoglycemic,hypolipidemic,hepatoprotective and nephroprotective effects.

Objective:This study retrospectively analyzed the clinical characteristics of patients newly diagnosed with acute myeloid leukemia (AML) who were admitted to the hematology intensive care unit (HCU) with critical illness. It also examined factors associated with critical illness and early mortality in these patients.Methods:Clinical data were collected from 91 newly diagnosed AML patients admitted to the HCU of the Department of Hematology, First Affiliated Hospital of Soochow University, from October 2020 to 2024. Reasons for HCU admission, major therapeutic interventions, and risk factors for critical illness and early mortality were analyzed.Results:The median time from diagnosis to HCU admission was 3 days ( IQR: 3–9 days), and the median HCU stay was 10 days ( IQR: 3–23 days). Of the 91 patients, 71 were admitted to the HCU before induction chemotherapy, while 20 were transferred to the HCU after its initiation. The leading causes of HCU admission were pulmonary infection (78.0% ), respiratory failure (44.0% ), hepatic insufficiency (28.6% ), renal insufficiency (27.5% ), disseminated intravascular coagulation (DIC; 25.3% ), and sepsis (23.1% ). Median Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) and SOFA scores at HCU admission were 14 ( IQR: 11–18) and the median Sepsis Related Organ Failure Assessment (SOFA) score was 7 ( IQR: 4, 10). Major HCU interventions included vasoactive drugs, noninvasive and invasive mechanical ventilation, continuous renal replacement therapy, therapeutic leukocyte clearance, and cardiopulmonary resuscitation. Among patients receiving induction chemotherapy, the composite complete remission rate was 65.4%, and the overall remission rate was 88.5%. Thirty-five (38.5% ) patients died within 28 days of HCU admission. Independent risk factors for 28-day mortality were DIC ( OR=9.350, 95% CI 1.999–43.745, P=0.005), sepsis ( OR=6.817, 95% CI 1.571–29.582, P=0.010), and cardiac insufficiency ( OR=12.281, 95% CI 2.385–63.254, P=0.003) . Conclusion:The main reason for HCU admission in newly diagnosed critically ill AML patients was pulmonary infection. Nearly 40% of patients experisenced early death, and DIC, sepsis, and heart failure were factors influencing early mortatlity.

Objective:To investigate the acute effects of persistent high exposure to atmospheric fine particulate matter (PM 2.5) on residents' outpatient visits for respiratory diseases. Methods:We collected daily outpatient records from 92 hospitals in 13 cities across the Beijing-Tianjin-Hebei region, along with daily PM 2.5, nitrogen dioxide (NO 2), and meteorological data from 2013 to 2018. Five persistent high PM 2.5 exposure scenarios were defined in terms of daily mean PM 2.5 concentrations (>75 μg/m 3 and >150 μg/m 3), duration (≥2 days and ≥3 days), and whether or not there was concurrent exposure to high levels of NO 2 (daily mean NO 2 concentration >50 μg/m 3). A two-stage statistical analysis strategy based on a generalized linear model was applied to conduct a time-series analysis to assess the exposure-response relationship between persistent high PM 2.5 exposure scenarios and residents' outpatient visits for a variety of respiratory diseases, and to estimate excess outpatient visits. Results:During the period, M ( Q1, Q3) PM 2.5 and NO 2 concentrations were 61.2 (42.3, 95.1) μg/m 3 and 40.2 (31.4, 54.4) μg/m 3, respectively, and the daily respiratory disease outpatient visits were 57 (52, 66) cases. When compared with non-permanent high PM 2.5 exposure periods, exposure scenarios with PM 2.5 >75 μg/m 3 and lasting for ≥2 days caused an increased risk of outpatient visits for respiratory diseases by 2.10% (95% CI: 1.44%-2.77%), and resulted in 43 787 (95% CI: 30 025-57 757) excess visits; in this scenario, the concurrent exposure to high levels of NO 2 had a greater acute effect on respiratory disease visits than the absence of exposure to high levels of NO 2 ( P<0.001). The risk of respiratory disease visits increased substantially by 4.41% (95% CI: 3.15%-5.68%) when the daily mean PM 2.5 concentration exceeded 150 μg/m 3 for ≥2 days. Subgroup disease analyses showed that scenarios with daily mean PM 2.5 concentrations exceeding 75 μg/m 3 for ≥3 days caused a significant increase in the risk of lower respiratory tract infections, chronic lower respiratory disease, and asthma visits. Conclusions:Sustained persistent high PM 2.5 exposure increases the risk of outpatient visits for various respiratory diseases; concurrent exposure to high concentrations of NO 2 leads to a greater risk of visiting the clinic, suggesting that the prevention and control of PM 2.5 pollution should be synchronized with the control of mobile source emissions, to synergistically manage the compound pollution of PM 2.5 and NO 2 in the atmosphere.

Objective:To compare the incidence of instrumentation-related complications and health-related quality of life following pelvic fixation using iliac screws (IS) or second sacral alar-iliac (S 2AI) screws in adult spinal deformity (ASD). Methods:A retrospective cohort study was conducted on 108 ASD patients who underwent posterior corrective fusion and fixation extending to the pelvis at Nanjing Drum Tower Hospital between September 2010 and April 2021. According to the type of pelvic fixation, patients were divided into an IS group ( n=34; 12 males, 22 females; mean age 53.7±11.1 years, range 28-73 years) and an S 2AI group ( n=74; 23 males, 51 females; mean age 52.8±8.6 years, range 27-72 years). Pre- and post- operative standing anteroposterior and lateral radiographs were evaluated for Cobb angle, coronal balance distance (CBD), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). At 2 years postoperatively, health-related quality of life were assessed using the Scoliosis Research Society-22 questionnaire (SRS-22), Oswestry disability index (ODI), and visual analogue scale (VAS) for pain. Instrumentation failure related to pelvic fixation during follow-up was recorded. Results:All patients completed follow-up. Mean follow-up duration was 28.5±3.6 months (range 24-37 months) in the IS group and 28.1±4.3 months (range 24-43 months) in the S 2AI group. Postoperatively, both groups showed significant improvement in Cobb angle, CBD, TK, LL, SVA, PT, and SS compared to baseline ( P<0.05), whereas PI remained unchanged ( t=0.664, P=0.509; t=1.227, P=0.222). Preoperative PT was greater in the IS group than in the S 2AI group (33.6°±8.7° vs. 29.3°±9.6°, t=2.228, P=0.028). No significant intergroup differences were observed in any other pre- or post- operative radiographic parameters ( P>0.05). Pelvic fixation failure occurred in 31 patients (28.7%, 31/108). Patients with fixation failure had a longer fusion segment extension than those without failure (12.0±2.8 vs. 10.8±2.4 segments; t=2.256, P=0.026). In the IS group, complications comprised 3 cases of screw loosening (8.8%), 2 of screw breakage (5.9%), and 4 of rod fracture within the pelvic region (11.8%), including 1 case with concurrent screw and rod failure. In the S 2AI group, there were 21 cases of screw loosening (28.4%) and 2 of screw breakage (2.7%). Screw loosening was less frequent in the IS group than in the S 2AI group (χ 2=5.154, P=0.023), whereas pelvic rod fracture was more common in the IS group (χ 2=9.041, P=0.003). Screw breakage rates did not differ significantly ( P>0.05). Mean VAS, ODI, and SRS-22 scores in the IS group were 3.2±2.4, 24.9%±18.8%, and 3.2±0.8, respectively; corresponding to 2.5±1.8, 18.9%±10.9%, and 3.3±0.6 in the S 2AI group. ODI was significantly higher in the IS group ( t=2.062, P=0.042), whereas VAS and SRS-22 were comparable ( P>0.05). Among S 2AI patients, VAS and ODI scores did not differ significantly between those with and without screw loosening ( P>0.05). Conclusions:The post-operative incidence of pelvic fixation failure following ASD surgery reached 28.7%. The predominant failure mode with S 2AI was screw loosening, whereas IS was more frequently complicated by rod fracture. Early postoperative health-related quality of life was superior with S 2AI screws compared with iliac screws.

Objective:To investigate the risk factors for postoperative coronal imbalance in patients with type A degenerative scoliosis and to refine the Qiu classification by reclassifying type A patients.Methods:A retrospective analysis was conducted on the clinical data of patients with type A degenerative scoliosis classified by the Qiu classification who underwent corrective surgery at our hospital from January 2017 to April 2022. A total of 69 patients were enrolled in the study, including 3 males and 66 females, with an age of 60.6±6.8 years (range: 47-71 years). Based on the preoperative CBD, type A patients were further divided into three subtypes: Aa with CBD≤1 cm, Ab with CBD>1 cm with C 7 plumb line deviation toward the concave side, and Ac with CBD>1 cm with C 7 plumb line deviation toward the convex side. The incidence of coronal imbalance was compared among subtypes. During follow-up, patients with CBD ≤3 cm were classified as balanced, and those with CBD>3 cm as imbalanced. Radiographic parameters including coronal Cobb's angle (CA), CBD, L 4 tilt angle, L 5 tilt angle, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and sagittal vertical axis (SVA) were measured in the standing radiographs preoperatively, 2-weeks postoperatively and 2-years follow-up. Differences in radiographic parameters between balanced and imbalanced groups were compared, and binary logistic regression was used to identify risk factors for postoperative coronal imbalance. Results:In the imbalanced Group (22 patients), there were 6 patients of type Aa (27%), 5 patients of type Ab (23%), and 11 patients of type Ac (50%), and in the balanced Group (47 patients), there were 20 patients of type Aa (43%), 18 patients of type Ab (38%), and 9 patients of type Ae (19%). The difference in subtype distribution between the two groups was significant (χ 2=6.939, P=0.029). The CBD in the imbalanced group was significantly larger than in the balanced group at the 2-years follow-up (4.18±0.86 cm vs. 1.31±0.78 cm, t=-13.813, P<0.001). The preoperative L 4 tilt angle was significantly larger in the imbalanced group compared to the balanced group (23.59°±6.86° vs. 17.64°±8.34°, t=-2.914, P=0.005). And the postoperative and 2-years follow-up L 4 tilt angles were also significantly larger than the balanced group (18.6°±5.5° vs. 11.5°±5.7°, t=-4.904, P<0.001; 18.0°±5.6° vs. 11.1°±5.7°, t=-4.691, P<0.001). Regression analysis identified the Ac type [ OR=3.937, 95% CI(1.07, 14.55), P=0.040] and excessive postoperative L 4 tilt angle [ OR=1.288, 95% CI(1.09, 1.52), P=0.003] as risk factors for postoperative coronal imbalance in type A patients. Conclusions:In the A-type of Qiu classification, patients with preoperative CBD>1 cm and trunk tilting towards the convex side (Ac type), as well as those with a large L 4 tilt angle after surgery, are more likely to experience coronal plane imbalance after surgery.

Objective:To investigate the difference of Roussouly ideal classification in predicting postoperative proximal junctional kyphosis (PJK) between adult degenerative spinal deformity patients with and without pelvic fixation and the potential reasons.Methods:From January 2017 to January 2020, a total of 95 patients (4 males, 91 females; with an average age of 62.03±6.30 years) with degenerative spinal deformities were retrospectively analyzed. There were 35 patients in the non-pelvic group (1 male, 34 females) and 60 patients in the pelvic group (3 males, 57 females). The radiographic parameters included coronal Cobb's angle (CA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), T1 pelvic angle (TPA), and proximal junctional angle (PJA) were measured in the standing radiographs preoperatively, postoperatively at 2 weeks, and 2-year follow-up. Changes in PT and SS were calculated for patients at 2 weeks and the 2-year follow-up. Based on the revised Roussouly classification, 95 patients were classified into different types preoperatively, postoperatively at 2 weeks, and during the 2-year follow-up. Changes in the classification of patients were documented postoperatively at 2 weeks. Roussouly types were determined using preoperative pelvic parameters, and a match was defined when the 2-week postoperative classification aligned with the ideal type. The occurrence of PJK and the relationship with classification matching were recorded in the group. Independent t-tests were used for intergroup comparisons of radiographic parameters, and chi-square tests were employed to assess classification changes and predictive accuracy of the Roussouly classification. Results:Preoperative PT, TPA and SVA in non-pelvic group were significantly smaller than those in pelvic group, and preoperative SS and LL larger than those in pelvic group ( P<0.05). The changes of PT and SS in non-pelvic group were significantly lower than those in pelvic group 2 weeks after surgery ( P<0.05). The proportion of classification changes in the pelvic group was significantly higher than that in the non-pelvic group (60% vs. 34%, χ 2=5.847, P=0.016). Among the 95 patients, a total of 29 experienced PJK during the follow-up, with 3 cases progressing to PJF. The incidence of PJK in mismatched patients was 37% with no significant difference compared with matched patients (19%) (χ 2=3.357, P=0.067). In the sacral spine group of 60 patients, 22 experienced PJK, with 3 cases progressing to PJF. Among them, 19 patients with PJK had a classification mismatch with the ideal classification at 2 weeks postoperatively. The PJK incidence was significantly higher in mismatched patients (45%) compared to matched patients (17%) (χ 2=4.429, P=0.035). In the non-pelvic group, 7 patients developed PJK, with 3 mismatched cases. The PJK incidence in mismatched vs. matched patients was 18% vs. 22%, showing no significant difference (χ 2=0.114, P=0.735). Conclusions:For the patients with degenerative spinal deformity, pelvic fixation leads to a more complete restoration of the ideal Roussouly classification. Restoration of the Roussouly type in patients with pelvic fixation is a reliable predictor of postoperative PJK. However, in patients without pelvic fixation, the alignment with the ideal Roussouly classification does not significantly correlate with PJK development.