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

Objective:To establish of a newmethod:for the rapid detection of H5N1-Avian Influenza virus by combining reverse transcription (RT), multiple cross displacement amplification (MCDA) and nanoparticle-based lateral flow biosensor (LFB).Methods:MCDA primers were designed based on gene sequences specific to Hemagglutinin (HA) and Neuraminidase (NA) in H5N1 avian influenza virus. The target genes HA and NA were amplified through reverse transcription and MCDA in one reaction system. Results were displayed by LFB. The assay was named as H5N1-mRT-MCDA-LFB. The reaction conditions of the H5N1-RT-MCDA-LFB method were optimized, and the sensitivity and specificity were also assessed.Results:The H5N1-RT-MCDA-LFB assay could achieve good amplification effect at a constant temperature of 65 ℃ for 40 minutes. The method had a lower limit of detection of 100 fg per reaction with 100-fold higher sensitivity than that of the RT-qPCR (lower limit of detection 10 pg per reaction). The assay was negative in detecting 28 common viruses, mycoplasmas, chlamydias, bacterias and funguses, except for H5N1. In addition, the H5N1-RT-MCDA-LFB method showed better validation in simulated clinical samples with a lower limit of detection at 1×10 2 copies/ml. Conclusion:The H5N1-RT-MCDA-LFB assay is a valuable molecular diagnostic technique for detecting H5N1 avian influenza virus due to its simplicity, rapidity, sensitivity and specificity.

Objective To compare the outcomes of transvaginal natural orifice transluminal endoscopic surgery(vNOTES)and laparoendoscopic single-site surgery(LESS)for total uterine excision in obese patients with benign uterine lesions,and to investigate the utility of vNOTES in this patient population.Methods A total of 100 obese patients(BMI>28.0 kg/m2)diagnosed with benign uterine lesions requiring total uterine and bilateral salpingectomy between January 2022 and January 2023 were included in this study.They were randomly assigned to two groups:the LESS group(n=51)and the vNOTES group(n=49).Patient demographics,surgical duration,intraoperative blood loss,changes in hemoglobin levels,pain scores,time to first flatus postoperatively,length of hospital stay,pelvic floor function,sexual quality of life,and postoperative complications were compared between the two groups.Results The two groups did not show any statistically significant differences in terms of blood loss,pre-and postoperative hemoglobin changes,pelvic floor function,sexual quality of life,or postoperative complications(P>0.05).However,the vNOTES group exhibited shorter surgical durations,time to first flatus postoperatively,and length of hospital stay compared to the LESS group(P<0.05).Additionally,the vNOTES group demonstrated lower intraoperative pain scores than the LESS group.(P<0.05).Conclusions In obese patients with benign uterine lesions,vNOTES total uterine excision surgery demonstrated shorter surgical durations and postoperative hospital stays,lower postoperative pain scores,and better adherence to the principles of en-hanced recovery after surgery(ERAS),indicating its potential for broader application.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

Objective:To investigate the inhibitory effect of RMT1-10-induced tolerogenic dendritic cells (Tol-DCs) in vitro on high-risk corneal allograft rejection in mice and its mechanism. Methods:One hundred SPF male BALB/c mice and fifty SPF male C57BL/6 mice were selected.Bone marrow-derived immature dendritic cells (imDCs) obtained from C57BL/6 mice were divided into imDCs group, mature dentritic cells (mDCs) group, RMT1-10 group, and IgG isotype control group.The imDCs in the four groups were cultured with no intervention, lipopolysaccharide, RMT1-10 and lipopolysaccharide, or IgG isotype antibody and lipopolysaccharide for 7 days according to grouping.The expression levels of different phenotypes of DCs including CD11c, CD80, CD86, major histocompatibility complex (MHC)-Ⅱ, T cell immunoglobulin and mucin domain containing molecule (Tim)-4 and CD103 in the four groups were detected by flow cytometry.The concentrations of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in the DCs supernatants were determined by enzyme-linked immunosorbent assay.A mixed lymphocyte culture system was established, and the stimulation index (SI) of CD4 + T cell proliferation stimulated with DCs was detected by cell counting kit 8 method.Corneal neovascularization was induced by corneal stromal suture in BALB/c mice, and the 80 mice with neovascularization in 4 quadrants growing into the middle and peripheral cornea were used as recipients.The recipient mice were randomized into imDCs group, mDCs group, RMT1-10 group, and IgG isotype control group using the random number table method, with 20 mice in each group.An injection of corresponding DCs (1×10 6 cells/100 μl) was administered to the recipient mice via the tail vein according to grouping.At 7 days following the injection, C57BL/6 mice were used as donors and penetrating keratoplasty was performed.Within one month after the operation, signs of corneal grafts rejection, including opacity, edema and neovascularization, were observed by slit lamp biomicroscopy and scored every day.At 21 days after the operation, 5 recipients selected from each group were subcutaneously injected with naive C57BL/6 splenocytes (1×10 6 cells/100 μl) behind the ear.The delayed type hypersensitivity (DTH) was evaluated by ear swelling at 24 hours after the subcutaneous injection.The use and care of experimental animals complied with the Regulations on the Management of Experimental Animals promulgated by the State Science and Technology Commission.This study protocol was approved by an Ethics Committee of the Affiliated Hospital of Chengde Medical University (No.CYFYLL2020055). Results:Compared with mDCs group, the expressions of CD80, CD86 and MHC-Ⅱ, and the percentage of Tim-4-positive cells in CD11c-positive cells were significantly decreased in RMT1-10 group, showing statistically significant differences (all at P<0.001). The percentage of Tim-4-positive cells were significantly decreased in RMT1-10 group than imDCs group, and the percentage of CD103-positive cells in RMT1-10 group was significantly higher than imDCs group, mDCs group and IgG isotype control group (all at P<0.001). The concentrations of IL-10 and TGF-β in the cell culture supernatant of RMT1-10 group were significantly higher than those of the other three groups, with statistically significant differences (all at P<0.001). There were statistically significant differences in the SI of CD4 + T cell proliferation simulated by DCs ( Fgroup=1 833.00, P<0.001; Fratio=230.40, P<0.001; Finteraction=3.06, P=0.01). The SI of DCs/CD4 + T cells ratio at 1∶5, 1∶10, 1∶20 and 1∶40 were all significantly lower in imDCs group than mDCs group, and were all significantly lower in RMT1-10 group than imDCs group (all at P<0.05). There was a statistically significant difference in corneal graft survival curve among various groups ( χ2=77.69, P<0.001). The survival rate of RMT1-10 group was significantly higher than that of imDCs group ( χ2=9.74, P=0.002), and the survival rate of imDCs group was significantly higher than that of mDCs group ( χ2=31.02, P<0.001). The ear swelling of recipient mice of positive control group, mDCs group, IgG isotype control group, imDCs group and RMT1-10 group was (503.6±17.2), (475.7±17.6), (456.2±18.8), (225.2±39.4), (118.1±12.6), and (106.4±7.4) μm, with a statistically significant difference among them ( F=377.10, P<0.001). The mice ear swelling was more serious in positive control group than mDCs group, more serious in IgG isotype control group than imDCs group, and more serious in imDCs group than RMT1-10 group (all at P<0.05). Conclusions:RMT1-10 can inhibit the rejection of high-risk corneal transplantation in mice, the mechanism of which may be attributed to inducing imDCs to transform into Tol-DCs in vitro and up-regulating the expression of TGF-β and IL-10, which promotes antigen-specific immune tolerance after adoptive transfer, thereby indirectly prolongs the survival of corneal grafts.

Objective:To observe the characteristics of choroidal thickness in patients with macular edema secondary to superior temporal branch retinal vein occlusion (BRVO-ME).Methods:A retrospective control study. From November 2020 to September 2021, 30 patients (30 eyes) with BRVO-ME (BRVO-ME group) were diagnosed by ophthalmology examination in Department of Ophthalmology, The Affiliated Hospital of Chengde Medical College and 14 healthy volunteers (28 eyes) were enrolled in the study. The choroidal thickness of macular area was measured by enhanced deep imaging technique of frequency domain optical coherence tomography. According to the subdivision of the diabetic retinopathy treatment group, the choroid within the 6 mm of the macular fovea was divided into three concentric circles with the macular fovea as the center, namely, the central area with the diameter of 1 mm, the inner ring of 1-3 mm and the outer ring of 3-6 mm. The inner ring area and the outer ring area are divided into upper, lower, nasal and temporal sides, respectively, which are denoted as S3, I3, N3, T3 and S6, I6, N6, T6, totaling 9 areas. To observe the distribution characteristics of choroidal thickness in different regions of two groups of eyes. The choroidal thickness of different macular regions was compared by independent sample t-test. Results:The choroidal thicknesses in the central area, S3, T3, I3, N3, S6, T6, I6, and N6 of the eyes in the control group and BRVO-ME group were 214.11±56.04, 207.89±57.92, 214.07±54.82, 207.14±61.54, 180.18±53.53, 204.25±59.60, 193.93±51.50, 190.54±51.21, 139.82±39.84 μm and 258.00±71.14, 256.43±68.70, 252.07±72.97, 244.37±68.49, 243.10±70.93, 247.20±68.36, 221.00±61.28, 223.77±58.64, 183.20±60.15 μm. In both groups, the choroidal thickness was the thickest in the central area, gradually thinning to the nasal side and temporal side, and the nasal choroidal thickness was thinner than other regions, and N6 area was the thinnest. Compared with the control group, the choroidal thickness of central area, S3, T3, I3, N3, S6, I6 and N6 in BRVO-ME group were significantly thicker ( t=-2.899, -2.229, -2.172,-3.250, -2.543, -2.292, -3.214; P<0.05), there was no significant difference in T6 area ( t=-1.814, P=0.075). Conclusion:The choroidal thickness of macular area in patients with BRVO-ME is thicker than that in normal subjects.

Objective:To investigate the short-term effects of articular injection of hyaluronic acid combined with glucocorticoid in patients with knee osteoarthritis.Methods:From October 2017 to June 2018, a total of 188 patients diagnosed with knee osteoarthritis received parallel articular injection. There were 60 cases with mild knee osteoarthritis, 72 with moderate and 56 with severe according to the WOMAC knee functional score. There patients were divided into group rank Ⅰ48 cases, Ⅱ 49 cases, Ⅲ 45 cases, Ⅳ 46 cases according to the knee joint X-ray Kellgren-Lawrence classification. The unified treatment regimen was 2.5 ml Sodium Hyaluronate (SHA) injection for the first time, SHA 2.5 ml and compound betamethasone injection (CBI) 1 ml for the second week, and 2.5 ml of SHA for the third week. WOMAC score and Lequesne index were used to evaluate joint function before the first injection and after SHA and SHA+CBI injection. The improvement rate of Lequesne index ≥30% or improvement rate of WOMAC score ≥25% was regarded as effective treatment.Results:Lequesne index and WOMAC score decreased gradually in the mild, moderate and severe groups after 3 weeks of injection. Among these patients, the improvement rates of Lequesne index after SHA injection and SHA+CBI injection were 36.44%±8.46% and 49.26%±13.75% in the mild group, 23.09%±12.61% and 30.66%±14.95% in the moderate group, and 10.50%±8.78% and 11.07%±6.52% in the severe group. The improvement rate of WOMAC score in the mild group after SHA injection and after SHA+CBI injection was greater than 25%. After SHA injection, the improvement rate of WOMAC score was 13.06%±10.21% in the moderate group, and 27.49%±13.61% after SHA+CBI injection. Those in severe group were all less than 25%. Kendall's staub correlation analysis results showed that there was a strong positive correlation between WOMAC function score and X-ray Kellgren-Lawrence classification ( r=0.744, P<0.001). The Lequesne index and WOMAC scores of the Kellgren-Lawrence X-ray classification decreased gradually after 3 weeks of injection. The improvement rate of Lequesne index period in group rank Ⅰ after SHA and SHA+CBI injection was 36.64%±10.05% and 52.00%±8.19%, respectively. That for group rank Ⅱ was 32.05%±8.09% and 41.95%±10.53%, group rank Ⅲ 16.93%±10.34% and 27.77%±10.25%, group rank Ⅳ 7.52%±5.53% and 7.60%±6.66%. The improvement rate of WOMAC score period in group rank Ⅰ after SHA and SHA+CBI injection was 29.48%±11.77% and 42.59%±13.55%, respectively. That for group rank Ⅱ was 26.72%±10.21% and 30.49%±16.90%, group rank Ⅲ 13.78%±5.96% and 23.05%±9.52%, group rank Ⅳ 4.77%±3.80% and 4.27%±4.23%. Conclusion:For mild or X-ray classification Ⅰ, Ⅱ knee osteoarthritis patients, articular injection SHA or SHA+CBI are effective. Further, SHA+CBI is better than single injection of SHA. SHA+CBI injection was effective for moderate knee osteoarthritis patients. For severe or X-ray classification Ⅲ, Ⅳ patients, SHA or SHA+CBI injection at interval are invalid.

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.

The dense extracellular matrix and high interstitial fluid pressure of tumor tissues prevent the ability of anti-tumor agents to penetrate deep into the tumor parenchyma for treatment effects. C-end rule (CendR) peptides can enhance the permeability of tumor blood vessels and tumor tissues binding to neuropilin-1 (NRP-1), thus aiding in drug delivery. In this study, we selected one of the CendR peptides (sequence RGERPPR) as the parent l-peptide and substituted d-amino acids for the l-amino acids to synthesize its inverso peptide (RGERPPR). We investigated the NRP-1 binding activity and tumor-penetrating ability of (RGERPPR). We found that the binding affinity of (RGERPPR) with NRP-1 and the cellular uptake was significantly higher than that of RGERPPR. Evans Blue tests revealed that (RGERPPR) exhibited improved tumor-penetrating ability in C6, U87 and A549 tumor-bearing nude mice. Using nude mice bearing A549 xenograft tumors as a model, we found that the rate of tumor growth in the group co-administered with (RGERPPR) and gemcitabine (Gem) was significantly lower than the gemcitabine-treated group with a tumor suppression rate (TSR%) of 55.4%. Together, our results demonstrate that (RGERPPR) is a potential tumor-penetrating peptide.