The accurate prediction of drug absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties represents a crucial step in early drug development for reducing failure risk. Current deep learning approaches face challenges with data sparsity and information loss due to single-molecule representation limitations and isolated predictive tasks. This research proposes molecular properties prediction with parallel-view and collaborative learning (MolP-PC), a multi-view fusion and multi-task deep learning framework that integrates 1D molecular fingerprints (MFs), 2D molecular graphs, and 3D geometric representations, incorporating an attention-gated fusion mechanism and multi-task adaptive learning strategy for precise ADMET property predictions. Experimental results demonstrate that MolP-PC achieves optimal performance in 27 of 54 tasks, with its multi-task learning (MTL) mechanism significantly enhancing predictive performance on small-scale datasets and surpassing single-task models in 41 of 54 tasks. Additional ablation studies and interpretability analyses confirm the significance of multi-view fusion in capturing multi-dimensional molecular information and enhancing model generalization. A case study examining the anticancer compound Oroxylin A demonstrates MolP-PC's effective generalization in predicting key pharmacokinetic parameters such as half-life (T0.5) and clearance (CL), indicating its practical utility in drug modeling. However, the model exhibits a tendency to underestimate volume of distribution (VD), indicating potential for improvement in analyzing compounds with high tissue distribution. This study presents an efficient and interpretable approach for ADMET property prediction, establishing a novel framework for molecular optimization and risk assessment in drug development.
Deep Learning

Objectives:To explore the value of improving the sensitivity of Epstein-Barr virus(EBV) DNA detection for the diagnosis and efficacy assessment of nasopharyngeal carcinoma.Methods:This was an observational study. The precision of the EBV DNA detection system used in this study was verified at the level of 100 copies/ml in accordance with the requirements of verification experiments, and the accuracy of the detection system was evaluated by comparing with digital PCR method. Totally 52 plasma samples were collected from patients who were newly diagnosed with undifferentiated non-keratinizing carcinoma of the nasopharynx at Nanfang Hospital of Southern Medical University from December 2021 to May 2022 in addition to156 plasma samples from nasopharyngeal carcinoma patients treated at the Radiotherapy Department of the hospital, and a retrospective analysis was also performed on 5 488 plasma samples that had been submitted for quantitative EBV DNA detection over the same period at the hospital. The effetcs of raising the EBV DNA detection threshold from 500 copies/ml to 100 copies/ml on the detection rate of nasopharyngeal carcinoma and the therapeutic efficacy assessment were compared.Results:The bias between the logarithmic values of the detected quantities and the target quantities was below±0.4 ( CV=6.94%) for the testings of 30 repetitions of the sample at the level of 100 copies/ml. The circulating EBV DNA of 156 patients with nasopharyngeal carcinoma was measured by the detection system and by digital PCR, and the results of the two methods showed good consistency ( r=0.95, P<0.001). By raising the EBV DNA detection threshold from 500 copies/ml to 100 copies/ml, the detection rate of nasopharyngeal carcinoma in untreated patients increased from 67.31% (35/52) to 82.69% (43/52). For nasopharyngeal carcinoma patients under treatment, the peripheral blood EBV DNA detection rates were 12.82% (20/156) and 23.72% (37/156) with detection thresholds of 500 copies/ml and 100 copies/ml, respectively. Conclusion:This research improved the EBV detection rate by increasing the sensitivity of EBV DNA assays, which is of great significance for the auxiliary diagnosis and therapeutic efficacy assessment in nasopharyngeal carcinoma patients.

Objective To construct HEK 293T cells that express tardigrade Dsup protein fused with green fluorescent protein copGFP in order to study the effect of Dsup protein on proliferation of HEK 293T cells.Methods The CRISPR/Cas9 gene knock-in system was constructed.The target gene fragments of Dsup,copGFP,EF1α and puromycin were amplified by PCR and inserted into pAAVS1-SFFV to construct the fusion vector of Dsup and copGFP,which was known as pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro.pAAVS1-SFFV-Dsup-copGFP-EF1 α-Puro and pAAVS1-CRISPR-Cas9 vector were co-transfected into HEK 293T cells before Dsup gene was inserted into the AAVS1 region of HEK 293T cells via homologous recombination.The HEK 293T cells expressing Dsup gene were obtained following puromycin selection,flow cytometry sorting and genome identification.The expression of Dsup at mRNA and protein levels and proliferation-related genes(MCM2,MCM4,PCNA,Ki-67)were examined to investigate the effects of Dsup gene on the proliferation of HEK 293T-Dsup-copGFP cells.Results The pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro recombinant vector was constructed,and the HEK 293T-Dsup-copGFP cells with Dsup gene inserted in the AAVS1 region were obtained,where both Dsup mRNA and protein were expressed.The cell proliferation rate of HEK 293T-Dsup-copGFP was higher than that of HEK 293T-Control-copGFP(P＜0.001).Further investigation revealed that the expressions of Ki-67 and MCM4 protein in HEK 293T-Dsup-copGFP were significantly higher than in the control group,indicating that the knock in of Dsup gene might enhance the proliferation ability of human cells by promoting the expression of Ki-67 and MCM4 protein.Conclusion A gene editing vector is constructed,and stable cell line HEK 293T-Dsup-copGFP for Dsup fusion expression with copGFP is established.The expression of Dsup gene in HEK 293T cells can promote cell proliferation,possibly by upregulating the expressions of Ki-67 and MCM4 protein.

Objective To analyze the risk factors of short-term re-obstruction after plastic stent placement by endoscopic retrograde cholangiopancreatography(ERCP)in patients with hilar malignant biliary obstruction.Methods A retrospective study was performed on clinical data of 93 patients with hilar malignant biliary obstruction who underwent ERCP biliary plastic stent placement from January 2015 to January 2024.Understanding the effects of general information,clinical characteristics,operative-related factors,and laboratory-related indicators on postoperative short-term re-obstruction.The dependent variable was whether biliary stent re-obstruction in short-term after operation,univariate and multivariate Logistic regression analysis were used to analyze the risk factors for the patients with hilar malignant biliary obstruction occurred re-obstruction in short-term after ERCP plastic stent placement.Results Among the 93 patients,49 patients had short-term recurrent biliary stent obstruction after plastic stent placement by ERCP and the recurrence rate was 52.7%.Univariate analysis showed that gender,types of malignant biliary strictures,preoperative cholangitis,no drainage before operation and endoscopic sphincterotomy(EST)during ERCP plastic stent placement,location of stent placement,fever within 24 h after ERCP plastic stent placement,the decrease less than 50%of total bilirubin(TBiL)at 2 weeks after operation,the decrease less than＜50%of γ-glutamyl transpeptidase(GGT)at 2 weeks after operation,GGT and alkaline phosphatase(ALP)by less than 50%at 2 weeks after operation were potential risk factors affecting for short-term re-obstruction after ERCP plastic stent placement in patients with hilar malignant biliary obstruction.Multivariate analysis showed that,no drainage before operation(O＾R=5.738,P=0.013),preoperative cholangitis(O＾R=5.347,P=0.025)and place stents on the left or on the right(O＾R=6.739,P=0.014;O＾R=9.719,P=0.005)were independent risk factors for short-term re-obstruction after ERCP plastic stent placement.Conclusion No drainage before operation,preoperative cholangitis,place stents on the left or on the right are independent risk factors for short-term re-obstruction after ERCP plastic stent placement in patients with hilar malignant biliary obstruction.Early identification of risk groups and timely intervention of risk factors in clinical practice are of great significance for the prevention of short-term re-obstruction after ERCP plastic stent placement in such patients.

Objective To investigate the clinical efficacy of different stents placement under endoscopic retrograde cholangiopancreatography(ERCP)in patients with malignant biliary obstruction(MBO)and the effect on patient survival time.Methods Clinical data of MBO patients treated with ERCP stent placement between January 2020 and March 2024 were collected,divided into recyclable stent group(33 cases),metal stent group(42 cases),and ordinary stent group(34 cases).Comparation of the three groups of preoperative and postoperative changes in liver function,complications of long-term cholangitis and pancreatitis,stent patency time,success rate of stent removal with a single clamping,survival time,monitoring follow-up situation.Results There was no statistically significant difference in the liver function of the three groups of patients before stent placement(P>0.05);One week after stent placement,the difference compared with preoperative between direct bilirubin(DBiL)and total bilirubin(TBiL)in the recyclable stent group and the metal stent group was significantly higher than that in the ordinary stent group,and the difference between the ordinary stent group and other two groups was statistically significant(P<0.05).The incidence of cholangitis in the recyclable stent group was the lowest,followed by the ordinary plastic biliary stent,and the metal biliary stent had the highest incidence of cholangitis,the incidence of cholangitis in the long term after stent placement was compared among the three groups of patients with a statistically significant difference(P<0.05).The incidence of postoperative pancreatitis in the three groups was not statistically significant(P>0.05).The success rate of stent removal with a single clamping was higher in the recyclable stent group than the ordinary stent group.Comparison of median stent patency time among the three groups,the difference was statistically significant(P<0.05).The metal stent group had the longest median patency time of 194.0 d,recyclable plastic stent had the second longest median patency time of 126.0 d,and ordinary plastic biliary stent had the shortest median patency time of 92.0 d.Median survival time among the three groups was statistically significant(P<0.05).The recyclable plastic biliary stent had the longest median survival time of 590.0 d,metal biliary stent had the second longest median survival time of 476.0 d,and ordinary plastic biliary stent had the shortest median survival time of 453.0 d.Conclusion Recyclable plastic biliary stent has a faster decrease in bilirubin index compared with the ordinary stent group after operation.And the recyclable plastic stent group has lower incidence of long-term cholangitis,higher success rate of one-time clamping of the stent,and more advantages in time to stent patency and survival time compared with ordinary plastic biliary stent,which is an effective choice of stenting modality for ERCP stent placement in patients with MBO.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Objective:To compare the efficacy and safety of low-intensity illumination 3D heads-up system-assisted pars plana vitrectomy (PPV) and traditional microscope eyepiece system-assisted PPV for proliferative diabetic retinopathy (PDR).Methods:A randomized controlled study was conducted.Forty patients (40 eyes) who were diagnosed as PDR and met the PPV standard were included in Xuzhou First People's Hospital from June to December 2022.The patients were randomly divided into 3D group and eyepiece group using a random number table method, with 20 eyes in each group.The eyes in 3D group underwent 3D heads-up system-assisted PPV, and the eyes in eyepiece group received traditional microscope eyepiece system-assisted PPV.The intravitreal injection of 0.5 mg(0.05 ml) ranibizumab was performed 6 or 7 days prior to three-channel 25G PPV for all the eyes.The brightness of endoilluminator was adjusted to minimum level during the surgical procedure, and the brightness of the optical fiber and chandelier in 3D group was set to 20%, while that in eyepiece group was 32% and 46%, respectively, and was further matched to the actual requirements of the surgery.The light intensity of optical fiber and chandelier was measured at 5 mm and 10 mm with a digital photometer.Best corrected visual acuity (BCVA) was measured before surgery and 7 days, 1 month and 3 months after surgery.Electroretinogram (ERG) was recorded by the Retiscan before surgery and 1 month after surgery to evaluate retinal function.Intraocular pressure and postoperative complications in both groups were compared.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University (No.xyy11[2022]027). Written informed consent was obtained from each subject prior to entering the cohort.Results:The BCVA was 2.21±1.13, 1.99±1.07, 1.26±0.86 and 0.98±0.65 in 3D group, and 1.89±0.95, 1.94±0.79, 1.42±0.80 and 1.31±0.79 in eyepiece group at before surgery and 7 days, 1 month, and 3 months after surgery, respectively.There was no significantly intergroup difference in BCVA ( Fgroup=0.022, P=0.884). The BCVA was significantly different at various time points before and after surgery ( Ftime=18.765, P<0.001). The BCVA was significantly improved at 1 and 3 months after surgery in 3D group and at 3 months after surgery in eyepiece group in comparison with before surgery, showing statistically significant differences (all at P<0.05). There were significant differences in the latency of dark-adapted 3.0 a-wave before and after surgery between two groups ( Htime=3.983, P=0.046), and the latency of dark-adapted 3.0 a-wave was shorter after surgery than before surgery in both groups (all at P<0.05). The light intensities of optical fiber and chandelier at 5 mm and 10 mm during surgery were lower in 3D group than in eyepiece group, and the differences were statistically significant (all at P<0.001). There was no significant difference in intraocular pressure between the two groups at different time points ( Fgroup=0.980, P=0.328; Ftime=2.706, P=0.062). There was no significant difference in the number of postoperative vitreous hemorrhage between the two groups ( χ2=0.960, P=0.327). Conclusions:Low-intensity illumination 3D heads-up system-assisted PPV has the same outcome as traditional microscope eyepiece system-assisted PPV for PDR.However, compared with the traditional microscope eyepiece system, the light intensity on the retina from low-intensity illumination 3D heads-up system is lower on the retina during surgery and therefore produce less light damage to retinal function of patients.

Objective:To explore the clinical value of aspirin combined with atorvastatin in the prevention of new onset atrial fibrillation after off-pump coronary artery bypass grafting (OPCABG).Methods:208 patients with coronary artery bypass grafting in our hospital from June 2019 to June 2021 were selected as the research subjects and divided by a random number table method into groups. The control group (104 cases) was treated with aspirin before operation, and the observation group (104 cases) was treated with aspirin and atorvastatin before operation. ECG monitoring was carried out continuously for 7 days of patients in the two groups, and the occurrence and duration of AF were recorded. The clinical therapeutic efficacy, incidence and adverse reactions of AF, left atrial diameter and high-sensitivity C-reactive protein (hs-CRP) level were observed before and after treatment.Results:The incidence of AF in the observation group was significantly lower than that in the control group, the difference was statistically significant ( P<0.05). There was no statistical significant difference in the starting time of AF between the two groups after operation ( P>0.05). The duration of AF in the observation group was better than that in the control group, the difference was statistically significant ( P<0.05). Before treatment, there was no statistical significant difference in left atrial diameter and hs-CRP level between the two groups ( P>0.05). After treatment, the left atrial diameter in the observation group returned to that before treatment, and there was no statistical significant difference in the same group ( P>0.05). The left atrial diameter in the control group was higher than that before treatment, and there was statistical significant difference in the same group ( P<0.05). The level of hs-CRP was lower than that in the control group, the difference was statistically significant ( P<0.05). There were no adverse reactions in both groups. Conclusion:Aspirin combined with atorvastatin has a significant effect in preventing new onset AF after OPCABG. It can reduce the incidence of postoperative AF, shorten the duration of AF, effectively control the inner diameter of left atrium, reduce the degree of postoperative inflammatory reaction, and has no adverse effects. It is worthy of clinical application.

ObjectiveTo investigate the feasibility of applying electronic nose technology to rapidly identify Bletillae Rhizoma and its approximate decoction pieces. MethodA total of 134 batches of Bletillae Rhizoma and its approximate decoction pieces， including 45 batches of Bletillae Rhizoma， 30 batches of Gastrodiae Rhizoma， 30 batches of Polygonati Odorati Rhizoma and 29 batches of Bletillae Ochraceae Rhizoma， were collected as test samples. The olfactory sensory data of the samples were collected by PEN3 electronic nose as the independent variable（X）. Based on the identification results of the 2020 edition of Chinese Pharmacopoeia and local standards， as well as the high performance liquid chromatography（HPLC） fingerprint and original purchase information of 134 batches of the decoction pieces， the benchmark data Y of the identification model were obtained， and four chemometric methods of principal component analysis-discriminant analysis（PCA-DA）， partial least squares-discriminant analysis（PLS-DA）， least square-support vector machine（LS-SVM） and K-nearest neighbor（KNN） were used to establish the binary identification model for 45 batches of Bletillae Rhizoma and 89 batches of non-Bletillae Rhizoma and the quadratic identification model of the four kinds of decoction pieces， that is， Y=F（X）. ResultAfter leave-one-out cross validation， the positive discrimination rates of the above four models were 97.01%， 97.01%， 98.51% and 97.01% in the binary identification， and 97.76%， 89.55%， 98.51% and 97.01% in the quadratic identification， respectively. The highest positive discrimination rate could reach 98.51% for the binary and quadratic identification models， and LS-SVM algorithm is both the optimal one， the most suitable kernel functions were chosen as radial basis function and linear kernel function， respectively. The optimal models discriminated well with no unclassified samples. ConclusionElectronic nose technology can accurately and rapidly identify Bletillae Rhizoma and its approximate decoction pieces， which can provide new ideas and methods for rapid quality evaluation of other decoction pieces.