Objective:To analyze the effects of low-molecular-weight heparin combined with insulin (LMWH+INS) and double filtration plasmapheresis (DFPP) on lipid profiles and clinical outcomes in patients with hypertriglyceridemic acute pancreatitis (HTG-AP) based on propensity score matching.Methods:The clinical data of 126 patients with HTG-AP from October 2022 to February 2024 in The Third Affiliated Hospital of Nanjing Medical University, Changzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing Traditional Chinese Medicine University and Changzhou First People's Hospital were retrospectively included. Patients were divided into LMWH+INS group ( n=87) and DFPP group ( n=39) according to the treatment. Propensity score matching was applied at a 1∶1 ratio. The repeated measures analysis of variance was conducted to assess dynamic changes of blood lipids within the 5 days of admission between the LMWH+INS and DFPP groups after matching. Clinical symptoms and outcomes were compared between the two matched groups following matching. Results:29 patients were included in both LMWH+INS group and DFPP group after propensity score matching. No statistically significant differences were observed in triglycerides (TG), acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, or bedside index for the severity of acute pancreatitis (BISAP) between the two groups (all P value >0.05), indicating comparability. Repeated measures analysis of variance revealed that TG and TC levels in the DFPP group were significantly lower than those in the LMWH+INS group at 2-5 days after admission [TG 2 d: (5.26±2.59) mmol/L vs (10.79±3.81) mmol/L, 3 d: (3.35±1.01) mmol/L vs (7.72±3.64) mmol/L, 4 d: (3.45±0.77) mmol/L vs (6.57±3.17) mmol/L, 5 d: (3.73±1.26) mmol/L vs (5.61±3.07) mmol/L; TC 2 d: (4.83±2.29) mmol/L vs (8.2±2.82) mmol/L, 3 d: (4.23±2.17) mmol/L vs (7.71±2.68) mmol/L, 4 d: (4.28±1.59) mmol/L vs (7.55±2.41) mmol/L, 5 d: (4.1±1.21) mmol/L vs (7.84±2.6) mmol/L], with a more rapid decrease. LDL levels in the LMWH+INS and DFPP groups showed similar trends, with significant decreases at 2 day after admission [(5.41±3.24) mmol/L vs (2.96±1.47) mmol/L, (4.99±3.51) mmol/L vs (2.47±1.53) mmol/L]. The differences mentioned above are all statistically significant (all P value <0.001). No significant changes were observed in HDL levels in either LMWH+INS and DFPP groups at 2-5 days after admission. After matching, the DFPP group had a significantly longer time of resuming feeding [3(2, 3) days vs 4(3, 6) days] and higher hospital cost [12113.87 (9055.31, 14401.84) yuan vs 28025.34 (25388.11, 36335.48) yuan] compared with the LMWH+INS group, with statistically significant differences. Conclusions:DFPP could reduce TG and TC levels more rapidly and effectively than LMWH combined with INS, but does not show an advantage in improving clinical outcomes and reducing hospitalization costs.

Objective:To analyze the effects of low-molecular-weight heparin combined with insulin (LMWH+INS) and double filtration plasmapheresis (DFPP) on lipid profiles and clinical outcomes in patients with hypertriglyceridemic acute pancreatitis (HTG-AP) based on propensity score matching.Methods:The clinical data of 126 patients with HTG-AP from October 2022 to February 2024 in The Third Affiliated Hospital of Nanjing Medical University, Changzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing Traditional Chinese Medicine University and Changzhou First People's Hospital were retrospectively included. Patients were divided into LMWH+INS group ( n=87) and DFPP group ( n=39) according to the treatment. Propensity score matching was applied at a 1∶1 ratio. The repeated measures analysis of variance was conducted to assess dynamic changes of blood lipids within the 5 days of admission between the LMWH+INS and DFPP groups after matching. Clinical symptoms and outcomes were compared between the two matched groups following matching. Results:29 patients were included in both LMWH+INS group and DFPP group after propensity score matching. No statistically significant differences were observed in triglycerides (TG), acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, or bedside index for the severity of acute pancreatitis (BISAP) between the two groups (all P value >0.05), indicating comparability. Repeated measures analysis of variance revealed that TG and TC levels in the DFPP group were significantly lower than those in the LMWH+INS group at 2-5 days after admission [TG 2 d: (5.26±2.59) mmol/L vs (10.79±3.81) mmol/L, 3 d: (3.35±1.01) mmol/L vs (7.72±3.64) mmol/L, 4 d: (3.45±0.77) mmol/L vs (6.57±3.17) mmol/L, 5 d: (3.73±1.26) mmol/L vs (5.61±3.07) mmol/L; TC 2 d: (4.83±2.29) mmol/L vs (8.2±2.82) mmol/L, 3 d: (4.23±2.17) mmol/L vs (7.71±2.68) mmol/L, 4 d: (4.28±1.59) mmol/L vs (7.55±2.41) mmol/L, 5 d: (4.1±1.21) mmol/L vs (7.84±2.6) mmol/L], with a more rapid decrease. LDL levels in the LMWH+INS and DFPP groups showed similar trends, with significant decreases at 2 day after admission [(5.41±3.24) mmol/L vs (2.96±1.47) mmol/L, (4.99±3.51) mmol/L vs (2.47±1.53) mmol/L]. The differences mentioned above are all statistically significant (all P value <0.001). No significant changes were observed in HDL levels in either LMWH+INS and DFPP groups at 2-5 days after admission. After matching, the DFPP group had a significantly longer time of resuming feeding [3(2, 3) days vs 4(3, 6) days] and higher hospital cost [12113.87 (9055.31, 14401.84) yuan vs 28025.34 (25388.11, 36335.48) yuan] compared with the LMWH+INS group, with statistically significant differences. Conclusions:DFPP could reduce TG and TC levels more rapidly and effectively than LMWH combined with INS, but does not show an advantage in improving clinical outcomes and reducing hospitalization costs.

Objective:To analyze the mutation spectrum and regional distribution of susceptibility pathogenic genes in Chinese chronic pancreatitis (CP) patients.Methods:A retrospective analysis was conducted on 1 758 sporadic CP patients who underwent gene sequencing for pathogenic mutations of four major susceptibility genes ( SPINK1, PRSS1, CTRC, and CFTR) at the First Affiliated Hospital of Naval Medical University from December 2010 to November 2022. Pathogenic mutations of four major susceptibility genes were detected by using the next-generation sequencing, and both known and novel pathogenic mutations were validated by Sanger sequencing. The ethnic and regional distributions of pathogenic mutations across different ethnic groups were compared. The ArcMap 10.7 software was used to provide the distribution map of common CP pathogenic mutations in China, and regional differences of these mutations were assessed. According to seven major geographical regions in China, we also evaluated the enrichment differences of CP pathogenic mutations in North China region, Northeast China region, East China region, Central China region, South China region, Southwest China region, and Northwest China region. Results:Among 1 758 CP patients, 50.23% (883/1 758) carried pathogenic mutations, and the SPINK1 pathogenic mutations were most predominated (39.31%). Among them, c.194+2T>C mutations accounted for 94.21% of all SPINK1 mutations. 32.59% (573/1 758) of patients carried single heterozygous mutation of one susceptibility gene, and 4.61% carried homozygous mutation of SPINK1 c.194+2T>C. There was no statistically significant difference on the overall pathogenic mutation carrying rate between Han and ethnic minority patients, whereas the mutation carrying rate of SPINK1 c.194+2T>C was significantly higher among Han patients than among ethnic minorities (37.48% vs 20.00%, P<0.05). Among 31 provinces and cities, the mutation carrying rate of CP patients in Tianjin, Guangdong, Yunnan, Hubei and Anhui were all higher than 60.00%. The SPINK1 mutations accounted for the highest proportion of pathogenic mutations across all provinces (33.33% to 61.54%), and SPINK1 c.194+2T>C was the most prevalent mutation. The mutation carrying rate of SPINK1 c.194+2T>C was higher than 40.00% in Jilin, Liaoning, Tianjin, Anhui, Jiangxi, Hubei, Henan, and Guangdong. Distribution analysis of seven geographic regions showed that the overall carrying rate of pathogenic mutations in North China region was significantly lower than that in Central China region (represented by Henan, Hubei, and Hunan; 38.38% vs 58.15%), and the differences were statistically significant ( P<0.05). Additionally, although the carrying rate of SPINK1 c.194+2T>C was highest in Central (41.85%) and Northeast China region (38.78%), no significant differences were found among different regions. Conclusions:Genetic factors was the main etiology of CP in China, with SPINK1 c.194+2T>C mutations being most prevalent. The carrying rates of common susceptibility genes of CP were highest in Central China region as well as SPINK1 c.194+2T>C mutation.

Objective:To analyze the mutation spectrum and regional distribution of susceptibility pathogenic genes in Chinese chronic pancreatitis (CP) patients.Methods:A retrospective analysis was conducted on 1 758 sporadic CP patients who underwent gene sequencing for pathogenic mutations of four major susceptibility genes ( SPINK1, PRSS1, CTRC, and CFTR) at the First Affiliated Hospital of Naval Medical University from December 2010 to November 2022. Pathogenic mutations of four major susceptibility genes were detected by using the next-generation sequencing, and both known and novel pathogenic mutations were validated by Sanger sequencing. The ethnic and regional distributions of pathogenic mutations across different ethnic groups were compared. The ArcMap 10.7 software was used to provide the distribution map of common CP pathogenic mutations in China, and regional differences of these mutations were assessed. According to seven major geographical regions in China, we also evaluated the enrichment differences of CP pathogenic mutations in North China region, Northeast China region, East China region, Central China region, South China region, Southwest China region, and Northwest China region. Results:Among 1 758 CP patients, 50.23% (883/1 758) carried pathogenic mutations, and the SPINK1 pathogenic mutations were most predominated (39.31%). Among them, c.194+2T>C mutations accounted for 94.21% of all SPINK1 mutations. 32.59% (573/1 758) of patients carried single heterozygous mutation of one susceptibility gene, and 4.61% carried homozygous mutation of SPINK1 c.194+2T>C. There was no statistically significant difference on the overall pathogenic mutation carrying rate between Han and ethnic minority patients, whereas the mutation carrying rate of SPINK1 c.194+2T>C was significantly higher among Han patients than among ethnic minorities (37.48% vs 20.00%, P<0.05). Among 31 provinces and cities, the mutation carrying rate of CP patients in Tianjin, Guangdong, Yunnan, Hubei and Anhui were all higher than 60.00%. The SPINK1 mutations accounted for the highest proportion of pathogenic mutations across all provinces (33.33% to 61.54%), and SPINK1 c.194+2T>C was the most prevalent mutation. The mutation carrying rate of SPINK1 c.194+2T>C was higher than 40.00% in Jilin, Liaoning, Tianjin, Anhui, Jiangxi, Hubei, Henan, and Guangdong. Distribution analysis of seven geographic regions showed that the overall carrying rate of pathogenic mutations in North China region was significantly lower than that in Central China region (represented by Henan, Hubei, and Hunan; 38.38% vs 58.15%), and the differences were statistically significant ( P<0.05). Additionally, although the carrying rate of SPINK1 c.194+2T>C was highest in Central (41.85%) and Northeast China region (38.78%), no significant differences were found among different regions. Conclusions:Genetic factors was the main etiology of CP in China, with SPINK1 c.194+2T>C mutations being most prevalent. The carrying rates of common susceptibility genes of CP were highest in Central China region as well as SPINK1 c.194+2T>C mutation.

Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8⁺ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.

Objective:To investigate the relationship between pancreatic fibrotic marker transforming growth factor-β(TGF-β) and platelet derived growth factor-BB(PDGF-BB) and serum glycated hemoglobin (HbA1c) levels in patients with type 3c diabetes mellitus secondary to chronic pancreatitis(CP-T3cDM).Methods:The clinical data of 39 patients with CP-T3cDM admitted to the Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University between February 2018 and August 2020 were collected, and the patients' age, gender, body mass index, duration of chronic pancreatitis and diabetes mellitus, smoking history, alcohol consumption history, serum HbA1c level at admission, degree of pancreatic atrophy, morphology of the main pancreatic duct, and treatment of diabetes mellitus were recorded. Serum TGF-β and PDGF-BB were detected by ELISA. Patients were divided into high and low level group according to the median TGF-β and PDGF-BB levels, respectively. Clinical characteristics of patients were compared between the TGF-β and PDGF-BB high and low level group. The correlation between TGF-β, PDGF-BB and HbA1c was analyzed by Spearman's correlation analysis.Results:A total of 39 CP-T3cDM patients were included; 35 were male and 4 were female. The age of first onset of chronic pancreatitis was (42±14) years old, and the duration of diabetes mellitus was 24(4, 36) months. The serum HbA1c level was (7.8±1.6)%, and the serum TGF-β and PDGF-BB levels were 20.5(10.5, 43.1) and 647.5(276.9, 1349.2)pg/ml, respectively. The serum HbA1c levels of patients in the high-level group of serum TGF-β and PDGF-BB were significantly higher than those in the corresponding low-level group [8.6%(7.4%, 9.9%) vs 6.7%(6.2%, 7.8%) and 8.6%(7.4%, 9.6%) vs 6.7%(6.1%, 7.8%), respectively] , and the difference was statistically different (both P value <0.01), while none of other indicators showed statistically significant differences between both groups. The correlation analysis showed that the levels of TGF-β and PDGF-BB were significantly positively correlated with HbA1c level ( r=0.45, 0.53, both P value <0.01). Conclusions:Increased pancreatic fibrosis in patients with CP-T3cDM was an important factor contributing to elevated blood glucose level. Patients with higher serum pancreatic fibrotic factors exhibited a significant increase in HbA1c level.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective:To establish and validate a radiomics nomogram based on MR for predicting cervical lymph node metastasis in laryngeal cancer.Methods:One hundred and seventeen patients with laryngeal cancer who underwent MR examinations and received open surgery and neck dissection between January 2016 and December 2019 were included in this study. All patients were randomly divided into a training cohort ( n=89) and test cohort ( n=28) using computer-generated random numbers. Clinical characteristics and MR were collected. Radiological features were extracted from the MR images. Enhanced T1 and T2WI were selected for radiomics analysis, and the volume of interest was manually segmented from the Huiyihuiying radiomics cloud platform. The variance analysis (ANOVA) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to reduce the dimensionality of the radiomics features in the training cohort. Then, a radiomic signature was established. The clinical risk factors were screened by using ANOVA and multivariate logistic regression. A nomogram was generated using clinical risk factors and the radiomic signature. The calibration curve and receiver operator characteristic (ROC) curve were used to confirm the nomogram′s performance in the training and test sets. The clinical usefulness of the nomogram was evaluated by decision curve analysis (DCA). Furthermore, a testing cohort was used to validate the model. Results:The radiomics signature consisted of 21 features, and the nomogram model included the radiomics signature and the MR-reported lymph node status. The model showed good calibration and discrimination. The model yielded areas under the ROC curve (AUC) in the training cohort, specificity, and sensitivity of 0.930, 0.930 and 0.875. In the test cohort, the model yielded AUC, specificity and sensitivity of 0.883, 0.889 and 0.800. DCA indicated that the nomogram model was clinically useful.Conclusion:The MR-based radiomics nomogram model may be used to predict cervical lymph node metastasis of laryngeal cancer preoperatively. MR-based radiomics could serve as a potential tool to help clinicians make an optimal clinical decision.

Objectives: To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer. Methods: The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ² test, survival analysis was carried by Kaplan-Meier and Log-rank test. Results: Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ²=288.60,P<0.01),N stage(χ²=68.10, P<0.01), vascular invasion(χ²=128.70, P<0.01)and neural invasion(χ²=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ²=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05). Conclusion With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.

The vegetative state is a complex condition with unclear mechanisms and limited diagnostic, prognostic, and therapeutic methods. In this study, we aimed to explore the proteomic profile of tears from patients in a traumatic vegetative state and identify potential diagnostic markers using tears-a body fluid that can be collected non-invasively. Using iTRAQ quantitative proteomic technology, in the discovery phase, tear samples collected from 16 patients in a traumatic vegetative state and 16 normal individuals were analyzed. Among 1080 identified tear proteins, 57 were upregulated and 15 were downregulated in the patients compared to the controls. Bioinformatics analysis revealed that the differentially-expressed proteins were mainly involved in the wound response and immune response signaling pathways. Furthermore, we verified the levels of 7 differentially-expressed proteins in tears from 50 traumatic vegetative state patients and 50 normal controls (including the samples used in the discovery phase) using ELISA. The results showed that this 7-protein panel had a high discrimination ability for traumatic vegetative state (area under the curve = 0.999). In summary, the altered tear proteomic profile identified in this study provides a basis for potential tear protein markers for diagnosis and prognosis of the traumatic vegetative state and also provides novel insights into the mechanisms of traumatic vegetative state.
Adult ; Aged ; Aged, 80 and over ; Biomarkers ; metabolism ; Chromatography, Liquid ; Enzyme-Linked Immunosorbent Assay ; Eye Proteins ; metabolism ; Female ; Humans ; Male ; Mass Spectrometry ; Middle Aged ; Persistent Vegetative State ; metabolism ; Proteome ; Proteomics ; ROC Curve ; Tears ; metabolism ; Young Adult