P-glycoprotein(P-gp)is a transmembrane protein widely involved in the absorption,distribution,metabolism,excretion,and toxicity(ADMET)of drugs within the human body.Accurate prediction of P-gp inhibitors and substrates is crucial for drug discovery and toxicological assessment.However,existing models rely on limited molecular information,leading to suboptimal model performance for predicting P-gp inhibitors and substrates.To overcome this challenge,we compiled an extensive dataset from public databases and literature,consisting of 5,943 P-gp inhibitors and 4,018 substrates,notable for their high quantity,quality,and structural uniqueness.In addition,we curated two external test sets to validate the model's generalization capability.Subsequently,we developed a multimodal graph contrastive learning(GCL)model for the prediction of P-gp inhibitors and substrates(MC-PGP).This framework integrates three types of features from Simplified Molecular Input Line Entry System(SMILES)sequences,molecular fingerprints,and molecular graphs using an attention-based fusion strategy to generate a unified mo-lecular representation.Furthermore,we employed a GCL approach to enhance structural representations by aligning local and global structures.Extensive experimental results highlight the superior perfor-mance of MC-PGP,which achieves improvements in the area under the curve of receiver operating characteristic(AUC-ROC)of 9.82％and 10.62％on the external P-gp inhibitor and external P-gp substrate datasets,respectively,compared with 12 state-of-the-art methods.Furthermore,the interpretability analysis of all three molecular feature types offers comprehensive and complementary insights,demonstrating that MC-PGP effectively identifies key functional groups involved in P-gp interactions.These chemically intuitive insights provide valuable guidance for the design and optimization of drug candidates.

P-glycoprotein (P-gp) is a transmembrane protein widely involved in the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of drugs within the human body. Accurate prediction of P-gp inhibitors and substrates is crucial for drug discovery and toxicological assessment. However, existing models rely on limited molecular information, leading to suboptimal model performance for predicting P-gp inhibitors and substrates. To overcome this challenge, we compiled an extensive dataset from public databases and literature, consisting of 5,943 P-gp inhibitors and 4,018 substrates, notable for their high quantity, quality, and structural uniqueness. In addition, we curated two external test sets to validate the model's generalization capability. Subsequently, we developed a multimodal graph contrastive learning (GCL) model for the prediction of P-gp inhibitors and substrates (MC-PGP). This framework integrates three types of features from Simplified Molecular Input Line Entry System (SMILES) sequences, molecular fingerprints, and molecular graphs using an attention-based fusion strategy to generate a unified molecular representation. Furthermore, we employed a GCL approach to enhance structural representations by aligning local and global structures. Extensive experimental results highlight the superior performance of MC-PGP, which achieves improvements in the area under the curve of receiver operating characteristic (AUC-ROC) of 9.82% and 10.62% on the external P-gp inhibitor and external P-gp substrate datasets, respectively, compared with 12 state-of-the-art methods. Furthermore, the interpretability analysis of all three molecular feature types offers comprehensive and complementary insights, demonstrating that MC-PGP effectively identifies key functional groups involved in P-gp interactions. These chemically intuitive insights provide valuable guidance for the design and optimization of drug candidates.

[Objective] To analyze the effects of different factors and red blood cell transfusion thresholds on the efficacy of neonatal red blood cell (RBC) transfusion, in order to provide more references for neonatal transfusions to better achieve rational and effective blood use. [Methods] A retrospective collection of data from 282 neonates who received RBC transfusions at our hospital from 2022 to 2023 was conducted, including birth weight, gestational age, number of blood transfusions, length of hospital stay, assisted ventilation during RBC transfusion, and laboratory test results before and after transfusion. SPSS software was used for statistical analysis to comprehensively analyze the impact of different factors on the efficacy of RBC transfusion in neonates. [Results] The results showed that the gestational age and weight of newborns at birth were negatively correlated with their length of hospital stay and the number of RBC transfusions during hospitalization. Newborns with younger gestational age and lower weight had longer hospital stays and more RBC transfusions during hospitalization. After administering RBCs according to the standard of 15 mL/kg, there was a statistically significant difference in the efficacy of RBC transfusion at different transfusion thresholds. In non-critical situations, RBC transfusions were ineffective when the pre-transfusion hemoglobin (Hb) level was >120 g/L. When the pre-transfusion Hb level was ≤70 g/L, RBC transfusions achieved higher efficacy in both critical and non-critical situations. [Conclusion] In critical situations, the group with pre-transfusion Hb values ≤ 70 g/L has the best RBC transfusion effect, while in non-critical situations, the group with pre-transfusion Hb levels between 81 and 90 g/L has the best RBC transfusion effect. Overall, the efficacy of RBC transfusion in non-critical situations is higher than that in critical situations.

AIM: To analyze the current status and influencing factors for insufficient hyperopia reserve in preschool children from Changzhi City, Shanxi Province, and to provide reference and basis for myopia prevention and control in this district.METHODS: A stratified cluster random sampling strategy was used to select 2 854 preschool children(5 708 eyes)from 29 child-care centers in Changzhi City between January and May 2024. Hyperopia reserve was assessed through measurements and questionnaire surveys. Totally 2 820 cases(5 640 eyes)were finally included, with 34 cases excluded(32 cases of uncooperativeness and 2 cases of distractibility). The univariate analysis and multivariate Logistic regression were performed to analyze the associated influencing factors of insufficient hyperopia reserve.RESULTS: A total of 580 preschool children with insufficient hyperopia reserve were detected, with an incidence of 20.57%. Logistic regression analysis revealed that male(OR=1.723, 95% CI: 1.419-2.093), maternal myopia(OR=2.210, 95% CI: 1.681-2.906), paternal myopia(OR=1.426, 95% CI: 1.059-1.921), myopia in both parents(OR=2.761, 95% CI: 2.110-3.612), preterm infants(OR=1.740, 95% CI: 1.294-2.342), the mean daily sleep duration <10 h(OR=1.272, 95% CI: 1.024-1.579), and the mean daily outdoor activity time <2 h(OR=1.222, 95% CI: 1.005-1.485)were risk factors for insufficient hyperopia reserve(all P<0.05). Conversely, using blackout curtains during the day and turning off lights at night(OR=0.598, 95% CI: 0.405-0.883)were identified to be protective factors(P<0.05).CONCLUSION: Sex, genetics, gestational age, sleep duration and environmental conditions, and outdoor activity time are potentially associated with insufficient hyperopia reserve in preschool children. Caregivers should prioritize the management of these risk factors to prevent the occurrence of myopia.

This study aims to prepare monoclonal antibody to S1 protein of porcine epidemic diar-rhea virus(PEDV).E.coli expression system and affinity chromatography were used to success-fully obtain purified recombinant PEDV S1 protein.After immunizing BALB/c mice,hybridoma technology and indirect ELISA were used to prepare and screen positive hybridoma cells.Finally,ascites antibodies were prepared by in vivo induction method.ELISA results showed that a total of 4 hybridoma cell lines with anti-PEDV S1 monoclonal antibody were screened,and they were named E6,G3,H6 and F2.The supernatant titers of all 4 hybridoma cell lines reached 1∶6 400.The monoclonal antibody H6 with higher antibody titers and more stable antibody secretion was selected for antibody type identification.It was found that monoclonal antibody H6 belongs to the IgG1 subclass and the light chain is the λ chain.The antibody titers that induced mouse ascites were 1∶106 and without cross-reaction with other proteins.Western blot results showed that the monoclonal antibody exhibited specific bands at 38 kDa with the recombinant S1 protein,PEDV QY2016,and PEDV CV777 strains.The IFA results also showed that the monoclonal antibody reacted with cells infected with PEDV QY2016 and PEDV CV777 strains,exhibiting a green fluo-rescent signal.The affinity constant of monoclonal antibody H6 was K=1.75×107 moL/L,indica-ting that the H6 strain had a good affinity and could be used for the development of subsequent di-agnostic antibodies.In summary,this study successfully prepared monoclonal antibodies that can specifically recognize PEDV S1 protein,which can be used for the antigen detection of PEDV and providing important test materials for the research of PEDV detection methods.

This paper introduces Professor WANG Jihong's clinical experience in treating refractory lateral epicondylitis using the Wang's crescent technique of blade needle. Based on the classical theories of Huangdi Neijing (the Yellow Emperor's Inner Classic) such as the "twelve sinew meridians" "short needling" and "shu needling", Professor WANG applies a self-designed blade needle with crescent needling method. This approach forms a distinctive treatment philosophy characterized by "sinew meridians as the foundation, selecting points at the pain site; using chicken-claw needling technique deliverd at both internal and external; integration of heaven, earth, and man, using both short and shu needling; treating tendon injuries and inflammation with the crescent technique of blade needle". It embodies the therapeutic concept of "treating tendons and bones simultaneously, harmonizing yin and yang", and shows unique advantages in the treatment of this condition.
Acupuncture Therapy/methods* ; Humans ; Tennis Elbow/therapy* ; Male ; Middle Aged ; Adult ; Needles ; Female ; Acupuncture Points

This article introduces the clinical experience of Professor WANG Jihong in treatment of post-stroke hypermyotonia with Lai's tongyuan therapy (therapy for removing obstruction and consolidating vital essence). Regarding the pathogenesis of this disease, Professor WANG Jihong emphasizes a "trinity" approach, "the mind disturbed, qi and blood unbalanced, and yuan (vital essence) not consolidated". In treatment, "the unblocking, conducting and nourishing are taken as the fundamental" to "prevent from over-dredging, balancing yin and yang, and avoiding over-replenishing". In clinical practice, the combined measure is adopted with acupuncture, tuina and herbal medicine. In acupuncture, the acupoints are selected according to the front-back combination of the points of the conception vessel and the governor vessel (basic prescription: Yintang [GV24⁺], Baihui [GV20] and Niesanzhen; prescription for promoting the governor vessel: Dazhui (GV14), Jinsuo [GV8], Xinshu [BL15], Pishu [BL20] and etc.; and the prescription for consolidating the vital essence: Danzhong (CV17), Zhongwan [CV12], Tianshu [ST25], Qihai [CV6]) and etc., as well as those on the four limbs for "opening, closing and pivoting of yin and yang" (on the upper limbs of the affected side: Jiquan [HT1], Jianyu [LI15], Quchi [LI11], Quze [PC3] and etc.; on the lower limbs of the affected side: Huantiao [GB30], Liangqiu [ST34], Xuehai [SP10], Yanglingquan [GB34]) and etc. The above points co-act on regulating the conception vessel and the governor vessel, and balancing yin and yang. Tuina is delivered on the governor vessel, the bladder meridian of foot-taiyang and wind points on the area between the head and nape, so as to promote the governor vessel, benefit the orifices, strengthen the spine and relax tendons. Herbal medicine works on nourishing the liver to soften tendons, nourishing blood to remove wind, regulating qi to replenish the spleen, consolidating the root to cultivate the vital essence, activating blood circulation to unblock meridians, and removing stasis to resolve phlegm. Tongyuan therapy provides a certain instruction in treatment of post-stroke hypermyotonia.
Humans ; Acupuncture Therapy ; Acupuncture Points ; Stroke/complications* ; Male ; Female ; Middle Aged ; Aged ; Drugs, Chinese Herbal ; Adult

Objective To investigate the nebulization characteristics of human interferon α1b for injection.To characterize and compare the delivery rate,total drug substance and the aerodynamic characteristics between the two types of nebulizer.Methods Connect two types of nebulizers with a breathing simulator,respectively,and simulate the breathing patterns of an infant and child.Measure the delivery rate,total delivered dose,and delivery uniformity.The aerodynamic properties of human interferon α1b for injection were evaluated by the next generation impactor(NGI).The content of human interferon α1b was quantified by double antibody sandwich ELISA.Results In the three batches of samples in infant mode,the delivery rate and total delivered dose determind by A nebulizer were 0.45,0.49,0.44 μg·min-1,3.06,3.21,3.81 μg,respectcively;and 0.12,0.14,0.16 μg·min-1,0.73,0.73,0.75 μg,respectcively by B nebulizer.In child mode,the delivery rate and total delivered doses determined by A nebulizer were 1.36,1.49,1.20 μg·min-1,7.44,7.17,and 6.54 μg,respectcively;and 0.37,0.36,0.43 μg·min-1,1.66,1.59,and 1.41 μg,respectcively by B nebulizer.In child and infant mode,the ten results of the total drug substance delivered determined by nebulizer A were both between 65%to 135%of the average.The FPD,FPF,MMAD,and GSD determined by A neublizer of three batch samples were 2.48,2.92,2.35 μg,59.0%,57.4%,59.1%,4.18,4.34,4.15 μm,1.94,1.98,2.01,respectively.The FPD,FPF,MMAD and GSD determined by B neublizer of three batches samples were 2.70,3.38,3.06 μg,67.6%,66.4%,66.3%,3.55,3.65,3.68 μm,2.03,2.04,2.06,respectively.Conclusions The data obtained in this research characterized the in vitro nebulization characteristics of human interferon α1b for injection and provided a theoretical basis and reference for in vitro study and clinical practice.The influence of different types of nebulizers on nebulization characteristics was evaluated as well.It is suggested that the quality standard of nebulizers be strictly formulated and the use of nebulizers be standardized.

Objective To investigate the nebulization characteristics of human interferon α1b for injection.To characterize and compare the delivery rate,total drug substance and the aerodynamic characteristics between the two types of nebulizer.Methods Connect two types of nebulizers with a breathing simulator,respectively,and simulate the breathing patterns of an infant and child.Measure the delivery rate,total delivered dose,and delivery uniformity.The aerodynamic properties of human interferon α1b for injection were evaluated by the next generation impactor(NGI).The content of human interferon α1b was quantified by double antibody sandwich ELISA.Results In the three batches of samples in infant mode,the delivery rate and total delivered dose determind by A nebulizer were 0.45,0.49,0.44 μg·min-1,3.06,3.21,3.81 μg,respectcively;and 0.12,0.14,0.16 μg·min-1,0.73,0.73,0.75 μg,respectcively by B nebulizer.In child mode,the delivery rate and total delivered doses determined by A nebulizer were 1.36,1.49,1.20 μg·min-1,7.44,7.17,and 6.54 μg,respectcively;and 0.37,0.36,0.43 μg·min-1,1.66,1.59,and 1.41 μg,respectcively by B nebulizer.In child and infant mode,the ten results of the total drug substance delivered determined by nebulizer A were both between 65%to 135%of the average.The FPD,FPF,MMAD,and GSD determined by A neublizer of three batch samples were 2.48,2.92,2.35 μg,59.0%,57.4%,59.1%,4.18,4.34,4.15 μm,1.94,1.98,2.01,respectively.The FPD,FPF,MMAD and GSD determined by B neublizer of three batches samples were 2.70,3.38,3.06 μg,67.6%,66.4%,66.3%,3.55,3.65,3.68 μm,2.03,2.04,2.06,respectively.Conclusions The data obtained in this research characterized the in vitro nebulization characteristics of human interferon α1b for injection and provided a theoretical basis and reference for in vitro study and clinical practice.The influence of different types of nebulizers on nebulization characteristics was evaluated as well.It is suggested that the quality standard of nebulizers be strictly formulated and the use of nebulizers be standardized.

This study aims to prepare monoclonal antibody to S1 protein of porcine epidemic diar-rhea virus(PEDV).E.coli expression system and affinity chromatography were used to success-fully obtain purified recombinant PEDV S1 protein.After immunizing BALB/c mice,hybridoma technology and indirect ELISA were used to prepare and screen positive hybridoma cells.Finally,ascites antibodies were prepared by in vivo induction method.ELISA results showed that a total of 4 hybridoma cell lines with anti-PEDV S1 monoclonal antibody were screened,and they were named E6,G3,H6 and F2.The supernatant titers of all 4 hybridoma cell lines reached 1∶6 400.The monoclonal antibody H6 with higher antibody titers and more stable antibody secretion was selected for antibody type identification.It was found that monoclonal antibody H6 belongs to the IgG1 subclass and the light chain is the λ chain.The antibody titers that induced mouse ascites were 1∶106 and without cross-reaction with other proteins.Western blot results showed that the monoclonal antibody exhibited specific bands at 38 kDa with the recombinant S1 protein,PEDV QY2016,and PEDV CV777 strains.The IFA results also showed that the monoclonal antibody reacted with cells infected with PEDV QY2016 and PEDV CV777 strains,exhibiting a green fluo-rescent signal.The affinity constant of monoclonal antibody H6 was K=1.75×107 moL/L,indica-ting that the H6 strain had a good affinity and could be used for the development of subsequent di-agnostic antibodies.In summary,this study successfully prepared monoclonal antibodies that can specifically recognize PEDV S1 protein,which can be used for the antigen detection of PEDV and providing important test materials for the research of PEDV detection methods.