OBJECTIVES: Multiple myeloma (MM) is a highly heterogeneous hematologic malignancy, with disease progression driven by cytogenetic abnormalities and a complex bone marrow microenvironment. This study aims to construct a prognostic model for MM based on transcriptomic data and lipid metabolism related genes (LRGs), and to identify potential drug targets for high-risk patients to support clinical decision-making. METHODS: In this study, 2 transcriptomic datasets covering 985 newly diagnosed MM patients were retrieved from the Gene Expression Omnibus (GEO) database. Univariate Cox regression and 101 machine learning algorithms were used for gene selection. An LRG-based prognostic model was constructed using Stepwise Cox (both directions) and random survival forest (RSF) algorithms. The association between the prognostic score and clinical events was evaluated, and model performance was assessed using time-dependent receiver operating characteristic (ROC) curves and the C-index. The added predictive value of combining prognostic scores with clinical variables and staging systems was also analyzed. Differentially expressed genes between high- and low-risk groups were identified using limma and clusterProfiler and subjected to pathway enrichment analysis. Drug sensitivity analysis was conducted using the Genomics of Drug Sensitivity in Cancer (GDSC) database and oncoPredict to identify potential therapeutic targets for high-risk patients. The functional role of key LRGs in the model was validated via in vitro cell experiments. RESULTS: An LRG-based prognostic model (LRG17) was successfully developed using transcriptomic data and machine learning. The model demonstrated robust predictive performance, with area under the curve (AUC) values of 0.962, 0.912, and 0.842 for 3-, 5-, and 7-year survival, respectively. Patients were stratified into high- and low-risk groups, with high-risk patients showing significantly shorter overall survival (OS) and event-free survival (EFS) (both P<0.001) and worse clinical profiles (e.g., lower albumin, higher β2-microglobulin and lactate dehydrogenase levels). Enrichment analysis revealed that high-risk patients were significantly enriched for pathways related to chromosome segregation and mitosis, whereas low-risk patients were enriched for immune response and immune cell activation pathways. Drug screening suggested that AURKA inhibitor BMS-754807 and FGFR3 inhibitor I-BET-762 may be more effective in high-risk patients. Functional assays demonstrated that silencing of key LRG PLA2G4A significantly inhibited cell viability and induced apoptosis. CONCLUSIONS LRGs serve as promising biomarkers for prognosis prediction and risk stratification in MM. The overexpression of chromosomal instability-related and high-risk genetic event-associated genes in high-risk patients may explain their poorer outcomes. Given the observed resistance to bortezomib and lenalidomide in high-risk patients, combination therapies involving BMS-754807 or I-BET-762 may represent effective alternatives.
Humans ; Multiple Myeloma/mortality* ; Prognosis ; Lipid Metabolism/genetics* ; Transcriptome ; Machine Learning ; Male ; Female ; Gene Expression Profiling ; Algorithms

Objective:This study evaluates the performance of chemiluminescence assay, which is designed to detect Hepatitis D Virus (HDV) Immunoglobulin G (IgG) antibodies.Methods:A comparative analysis was conducted among chemiluminescence anti-HDV IgG reagent, the magnetic particle-based domestic reagent A and domestic reagent B, and the Robo Gene HDV RNA kit, using 1909 HBsAg-positive plasma samples. This comparison aimed to delineate clinical specificity and detection accuracy. The anti-HDV IgG reagent precision was assessed at three different concentration levels following the Clinical Laboratory Standards Institute EP5-A2 guidelines. The specificity of the assay was validated using 200 HAV IgM positive, 545 HBsAg-positive but anti-HDV IgG-negative, 350 anti HCV positive plasma samples and 200 healthy human blood samples. Additionally, a concordance study was conducted with 545 HBsAg-positive and 37 anti-HDV IgG-positive plasma samples, comparing the anti-HDV IgG reagent against reagent A.Results:1 909 HBsAg-positive plasma samples were tested using 3 anti HDV IgG reagent and 1 HDV RNA reagent, 19 samples were identified as anti-HDV IgG-positive. The anti-HDV IgG demonstrated superior accuracy and specificity. The assay exhibited excellent precision, with intra-assay coefficient of variation (CV) values ranging from 1.57% to 4.30%, and inter-assay CV values between 1.71% and 4.67% for detecting samples at high, medium, and low concentration levels. Concordance with Reagent A showed consistent results in both positive and negative detections.Conclusion:In this study, the anti-HDV IgG reagent (chemiluminescence method) displayed outstanding specificity in detecting clinical samples and exhibited a high conformity rate with commercialized reagents, making it potentially suitable for screening anti-HDV IgG in HBsAg-positive samples.

Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.

Objective:To study the efficacy and safety of laparoscopic surgery in treatment of recurrent hepatocellular carcinoma.Methods:The clinical data of 58 patients with recurrent hepatocellular carcinoma who underwent surgical treatment from January 2010 to January 2018 at Hunan Provincial People’s Hospital were retrospectively analyzed. There were 50 males and 8 females, ranging in age from 28 to 78 (53.0±10.8) years old. Patients were divided into laparoscopic group ( n=27) and laparotomy group ( n=31) according to different surgical procedures. The differences in operative time, intraoperative blood loss, hospital stay, postoperative anal exhaustion time, postoperative complications and prognosis between the two groups were compared. Results:The intraoperative blood loss of laparoscopy group and laparotomy group were 100.0(50.0, 400.0) ml vs 300.0(100.0, 500.0) ml, the postoperative anal exhaustion time were (2.7±0.6) d vs (3.3±0.6) d, the hospital stay were (14.8±3.8) d vs (21.4±6.3) d, and these differences were statistically significant (all P<0.05). The operative time of the two groups were (243.4±27.2) min vs (217.5±34.7) min, with no statistical significance ( t=0.59, P=0.344). There were no significant differences between the two groups in postoperative complications (bile leakage, abdominal infection, hemorrhage, pleural effusion and hepatic encephalopathy) (all P>0.05); thetumor free survival, 1-year, and 3-year overall survival rates of the two groups were also not significantly different (both P>0.05). Conclusion:Laparoscopic surgery is safe and effective in the treatment of recurrent hepatocellular carcinoma, and its prognosis is similar to laparotomy, its complications are not significantly increased, which is worthy of promotion in clinic.

Objective:To investigate the value of the extrahepatic bile duct and main pancreatic duct segment patterns on magnetic resonance cholangiopancreatography (MRCP) for differentiating the periampullary carcinoma (PAC).Methods:The clinicopathologic data of 125 patients with PAC who were admitted to Wuxi No.2 People’s Hospital from June 2013 to December 2021 were retrospectively analyzed, including 72 males and 53 females, aged (64.9±8.6) years. According to its anatomy, the extrahepatic bile duct (B) was divided into suprapancreatic and intrapancreatic (including ampullary) segments, and the main pancreatic duct (P) was divided into tail-body and head segments. MRCP patterns: i. the extrahepatic bile duct or main pancreatic duct visible without dilatation, ii. cutoff of the distal extrahepatic bile duct or main pancreatic duct with upstream dilatation, iii. cutoff of the intrapancreatic or head segment with upstream dilatation and remnant intrapancreatic or head segments invisible, iv. cutoff of the intrapancreatic or head segment with upstream dilatation and nondilated remnant intrapancreatic or head segments, were represented as 0, 1, 2, and 3, respectively. Segment patterns of B1/P0+ B1/P1, B0/P2+ B0/P3+ B2/P2+ B2/P3+ B3/P3, B3/P0, and B0/P0+ B2/P0 on MRCP were compared in PAC patients.Results:Of the 125 patients, there were 57 (45.6%) with pancreatic head carcinoma, 36 (28.8%) with ampullary carcinoma, 20 (16.0%) with distal cholangiocarcinoma, and 12 (9.6%) with periampullary duodenal carcinoma. Segment patterns of B0/P2+ B0/P3+ B2/P2+ B2/P3+ B3/P3 were found in 52 patients with pancreatic head carcinoma (91.2%, 52/57), with a significant difference between PAC (χ 2=110.66, P<0.001). Segment patterns of B1/P0+ B1/P1were found in 36 patients with ampullary carcinoma (100.0%, 36/36), fallowed by 11 (91.7%, 11/12) with periampullary duodenal carcinoma, with a significant difference between PAC (χ 2=129.95, P<0.001). Segment pattern of B3/P0 presented in 16 patients with distal cholangiocarcinoma (80.0%, 16/20), with a significant difference between PAC (χ 2=62.45, P<0.001). The segment patterns of B0/P0+ B2/P0 were only seen in 3 of 57(5.3%) patients with pancreatic head carcinoma. Conclusion:On MRCP, cutoff of the head segment with upstream dilatation and remnant head segment invisible or nondilated indicates the pancreatic head carcinoma. Cutoff of the intrapancreatic segment with upstream dilatation, remnant intrapancreatic segment visible, and main pancreatic duct nondilated, indicates the distal cholangiocarcinoma. And cutoff of the distal extrahepatic segment with upstream dilatation and main pancreatic duct dilatation or not, indicates the ampullary or periampullary duodenal carcinoma.

Objective:To investigate the risk factor of hepatocellular carcinoma (HCC) with vessels encapsulating tumor clusters (VETC) and the application value of its risk scoring model.Methods:The retrospective cross-sectional study was conducted. The clinicopathological data of 149 patients with HCC who were admitted to two medical centers, including 97 cases in the Jiangnan University Medical Center and 52 cases in the Affiliated Xingtai People′s Hospital of Hebei Medical University, from January 2017 to April 2020 were collected. There were 116 males and 33 females, aged (58±12)years. There were 74 cases with VETC and 75 cases without VETC. Observation indica-tors: (1) clinical characteristics of patients with and without VETC; (2) imaging features of patients with and without VETC; (3) multivariable analysis of HCC patients with VETC; (4) construction of VETC related risk scoring model and its performance evaluation; (5) postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolutes, and comparison between groups was conducted using the chi-square test and continuous correction chi-square test. Variables of clinical and imaging characteristics with statistically signifi-cant were included in the multivariate analysis. Multivariate analysis was conducted using the Logistic regression model of backward stepwise selection. VETC related risk scoring model was constructed based on the results of Logistic regression model. The receiver operating characteristic (ROC) curve was drawn, and the area under curve (AUC), the sensitivity, specificity, accuracy and their 95% confidence interval ( CI) were calculated. The maximizing Youden index was the optimal cutoff value for VETC prediction. The Hosmer Lemeshow goodness of fit test was used to assess the consistency between VETC risk scoring model predicted VTEC status and the true VETC status. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Results:(1) Clinical characteristics of patients with and without VETC. Cases with postoperative albumin <36 g/L were 57 in patients with VETC, versus 68 in patients without VETC, respectively, showing a significant difference between them ( χ2=5.13, P<0.05). (2) Imaging features of patients with and without VETC. Cases with lesion imaging presence as nonperipheral washout, cases with lesion imaging presence as mosaic architecture, cases with lesion imaging presence as intratumoral hemorrhage, cases with lesion imaging presence as corona enhancement, cases with lesion imaging presence as non-smooth tumor margin, cases with lesion imaging presence as peritumoral enhancement in arterial phase, cases with lesion imaging presence as intratumoral arteries, cases with lesion imaging presence as peritumoral hypointensity in hepatobiliary phase, cases with lesion imaging enhancement type as uniform low enhancement, uniform high enhance-ment, heterogeneous enhancement with septations and heterogeneous enhancement with irregular ring-like structures, cases with intratumoral necrosis or ischemic, cases with tumor diameter >5 cm were 73, 35, 33, 15, 39, 28, 42, 27, 4, 5, 27, 38, 45, 46 in patients with VETC, versus 64, 16, 13, 3, 19, 15, 9, 13, 9, 35, 5, 26, 10, 10 in patients without VETC, respectively, showing significant differences in the above indicators between them ( χ2=8.92, 11.15, 12.97, 9.28, 11.74, 5.77, 33.14, 6.96, 41.79, 36.05, 37.86, P<0.05). (3) Multivariable analysis of patients with VETC. Results of multivariable analysis showed that lesion imaging enhancement as heterogeneous enhancement with septations, lesion imaging enhancement as heterogeneous enhancement with irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm were independent risk factors influen-cing patients with VETC ( odds ratio=4.18, 7.62, 4.23, 4.08, 95% CI as 1.60?11.60, 2.00?31.70, 1.71?10.90, 1.60?10.80), P<0.05). (4) Construction of VETC related risk scoring model and its performance evaluation. The VETC related risk scoring model was constructed as (heterogeneous enhancement with septations, presence: 1.0, absence: 0)+(heterogeneous enhancement with irregular ring-like structures, presence: 1.5, absence: 0)+(intratumoral necrosis or ischemia, presence: 1.0, absence: 0)+(main tumor diameter >5 cm, presence: 1.0, absence: 0). The AUC, sensitivity, specificity, and accuracy of VETC related risk scoring model were 0.86 (95% CI as 0.80?0.92), 79.7% (95% CI as 69.2%?87.3%), 80.0% (95% CI as 69.6%?87.5%) and 79.9% (95% CI as 72.7%?85.5%), respectively. Results of Hosmer-Lemeshow goodness of fit test showed a good consistency between VETC risk scoring model predicted VETC status and true VETC status ( P>0.05). (5) Postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. All 149 patients were followed up for 29(range, 26?35)months. The time to tumor recurrence and 2-year cumulative tumor recurrence rate of 149 patients were 29(range, 24?33)months and 43.0%, respectively. The 2-year tumor cumulative recurrence rate of patients with and without VETC predicted by risk scoring model was 47.8% and 37.9%, respectively, showing a significant difference between ( χ2=3.90, P<0.05). The 2-year cumulative tumor recurrence rate of patients with and without VETC confirmed by postoperative histopathological examination was 47.4% and 38.1%, respectively, showing a significant difference between ( χ2=4.20, P<0.05). Conclusions:Lesion imaging enhancement as heterogeneous enhancement with septations or irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm are independent risk factors influen-cing HCC patients with VETC. The proposed risk scoring model based on those three risk factors achieves an optimal preoperative diagnostic performance.

Objective:To investigate the value of machine learning-based computed tomography (CT) images radiomics analysis in preoperative evaluation of surgical portal vein-superior mesenteric vein (PV-SMV) invasion in patients with pancreatic ductal adenocarcinoma (PDAC).Methods:The retrospective study was conducted with 156 consecutive PDAC patients who were underwent surgery at the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University between January 2010 and July 2021. There were 95 males and 61 females, with the age of (65.7±8.2) years. Patients were randomly split into training set and validation set by a ratio of 3∶2. Minimum redundancy maximum relevance was used to select radiomic features, which were extracted from contrast-enhanced CT images. Five machine learning classifiers were developed, and those models' area under the curve (AUC) values were compared with the conventional radiologic-feature-based evaluation.Results:Ninety-four and 52 patients were included into the training set and validation set, respectively. Their PV-SMV invasion rates were confirmed by intraoperative exploration with 31.9%(30/94) and 40.3%(25/61), respectively. Five models: LASSO regression, random forest, support vector machine, k-nearest neighbor and Naive Bayesian, were established based on ten features from CT images radiomics, and LASSO regression model achieved the highest AUC value compared with the other four models (all P<0.05). Compared with the conventional radiologic evaluation, the LASSO regression model had higher AUC (0.920 vs. 0.752) and sensitivity (92.0% vs. 86.5%)(both P<0.05). Conclusion:Machine learning-based CT images radiomics analysis can be used to evaluate PV-SMV invasion status preoperatively in PDAC. The LASSO regression model showed better performance than the conventional radiologic evaluation.

Objective:To compare between laparoscopic and open pancreaticoduodenectomy in the treatment of distal cholangiocarcinoma.Methods:The clinical data of laparoscopic pancreaticoduodenectomy (LPD group, n=101) and open pancreaticoduodenectomy (OPD group, n=99) in patients with distal cholangiocarcinoma who underwent pancreaticoduodenectomy at Hunan people's Hospital from Jan 2015 to Dec 2019 were analyzed retrospectively. The operation time, intraoperative blood loss, number of lymph node dissection, R 0 resection rate, postoperative hospital stay, postoperative complications and overall survival rate were compared between the two groups. Results:The operation time was (475.0±90.7) min and (444.8±63.3) min, the intraoperative blood loss was (350.9±397.9) ml and (546.7±642.9) ml, the postoperative hospital stay was (11.5±4.7) d and (13.3±5.1) d, the differences were statistically significant ( P<0.05).The number of lymph node dissection was 14.8±3.0 and 15.4±2.4, the R 0 resection rate was 93.1% and 96.0%, respectively, and there was no significant difference ( P>0.05). There was no significant difference in the incidence of residual complications ( P>0.05). During the follow-up of 5-64 months, the OS of 1, 3 and 5 years in the two groups were 90.4%, 41.3%, 20.6% and 94.3%, 50.8% and 24.7%, respectively. ( P>0.05). Conclusions:LPD is safe and feasible in the treatment of distal cholangiocarcinoma, and its short-term curative effect, curative effect and long-term overall survival rate are similar to those of OPD.

Objective:To compare the safety and efficacy of laparoscopic versus open pancreaticoduodenectomy.Methods:The clinical data of 989 patients who underwent pancreaticoduodenectomy at Hunan People's Hospital from January 2015 to December 2019 were analyzed retrospectively. There were 349 patients in the laparoscopic pancreaticoduodenectomy (LPD) group and 640 patients in the open pancreaticoduodenectomy (OPD) group. Propensity score matching (PSM) was used to match the baseline data of the two groups at a 1: 1 ratio. Data including operation time, intraoperative bleeding, postoperative hospital stay, bile leakage, pancreatic fistula and wound infection were compared between the two groups.Results:After PSM, there were 345 patients in each of the 2 groups. When the LPD group was compared with the OPD group, there were no significant differences in postoperative mortality, reoperation, intraoperative blood transfusion, pancreatic fistula, bile leakage, abdominal hemorrhage, abdominal abscess, severe complications, and pulmonary complication rates. The number of lymph node dissected, R 0 resection and overall survival rates between the two groups were also not significantly different ( P>0.05). However, the operation time of the LPD group (478.2±91.3) min was significantly longer than that of the OPD group (410.8±62.0) min ( P<0.05). On the other hand, the postoperative hospitalization time (10.8±4.3) d, intraoperative bleeding (322.0±362.6) ml, wound infection rate 1.2% (4/345) in the LPD group were significantly better than those in the OPD group [postoperative hospitalization time (12.5±7.9) d, intraoperative bleeding (478.8±570.2) ml, and wound infection rate 5.8% (20/345)] ( P<0.05) . Conclusion:LPD was safe and feasible, and it achieved similar curative effect as OPD.

Objective To study the role of MDCT with 3D fusion images in the preoperative evaluation of pancreaticoduodenectomy.Methods 37 patients who underwent pancreaticoduodenectomy from March 2016 to May 2018 in the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University were included in this retrospective study.All patients underwent a dual-phase enhanced MDCT before operation.The volume data of enhanced MDCT were transmitted to a dedicated CT post-processing workstation.The 3D images,including the tumor,pancreas,portal vein system,arterial system,pancreatic and biliary tract,were reformatted respectively before the fusion imaging.Two reviewers analyzed the tumor location and its spatial relations with the pancreaticobiliary system,peripancreatic vessels and vascular variations by means of zooming,rotating,splitting and transparent displaying on fusion images.Then,the assessed items were compared to the surgical and pathological findings.Results The 3D fusion images of 37 patients in this study depicted the tumor,pancreas,peripancreatic vessels and pancreatic and biliary tract clearly.Compared with the intraoperative and pathological findings,the accuracy of both tumor detection and localization with the 3D fusion images was 100％.To compare the intraoperative findings,visualization and variation detection of the celiac,splenic,common hepatic,gastroduodenal,hepatic,and superior mesenteric arteries,and the superior mesenteric and portal veins were all 100％.Visualizations of the anterior superior pancreaticoduodenal artery (ASPDA),posterior superior pancreaticoduodenal artery (PSPDA),inferior pancreaticoduodenal artery (IPA) and dorsal pancreatic artery (DPA) were 85.7％,82.8％,72.2％ and 75.8％,respectively.Conclusion The MDCT 3D fusion imaging technology allowed one stop preoperative assessment of pancreaticoduodenectomy,especially in clearly outlining the tumor location and its spatial relations with the surrounding surgical anatomies before surgery.