Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the present study,an innovative natural product virtual screening-interaction-phenotype(NP-VIP)strategy that integrates virtual screening,chemical proteomics,and metabolomics to identify and validate the bioactive targets of NPs.This approach reduces false positive results and enhances the ef-ficiency of target identification.Salvia miltiorrhiza(SM),a herb with recognized therapeutic potential against ischemic stroke(IS),was used to illustrate the workflow.Utilizing virtual screening,chemical proteomics,and metabolomics,potential therapeutic targets for SM in the IS treatment were identified,totaling 29,100,and 78,respectively.Further analysis via the NP-VIP strategy highlighted five high-confidence targets,including poly[ADP-ribose]polymerase 1(PARP1),signal transducer and activator of transcription 3(STAT3),amyloid precursor protein(APP),glutamate-ammonia ligase(GLUL),and glutamate decarboxylase 67(GAD67).These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM.The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research,proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

Objective:To analyze the genetic variant characteristics of primary immunodeficiency diseases (PID) in families from Henan Province.Methods:This study conducted a retrospective analysis of 19 PID pedigrees referred to the Prenatal Diagnosis Center at Henan Provincial People's Hospital between January 2016 and March 2024. Among the 19 families, 13 underwent prenatal diagnosis at our hospital, while the remaining six received genetic counseling based on third-party genetic testing reports (confirmed by our institution's laboratory). The clinical data from these families were analyzed, and descriptive statistical analysis was applied to the data.Results:Among the 19 PID families, there were seven cases of combined immunodeficiency, three immunodeficiency syndromes, three phagocyte deficiencies, three antibody-dominant immunodeficiencies, and three immunodysregulatory disorders, involving a total of 12 genes ( IL2RG, ADA, RAG2, STAT3, SMARCAL1, ATM, POLA1, CYBB, BTK, RAB27A, LRBA, IL10R). A total of 25 genetic variants were identified, including 11 novel variants not previously documented in the ClinVar and HGMD professional databases. The novel variants comprised: IL2RG gene mutations (Exon5_8del and c.903_904delinsCT leading to p.E302*), ADA gene mutation (c.884A>G resulting in p.D295G), RAG2 gene mutation (c.513dupA causing p.W172Mfs3), POLA1 gene mutation (c.25+5G>C), CYBB gene mutations (c.824G>A/p.G275D and c.472A>T/p.K158), BTK gene mutations (c.522_523insC/p.A175fs and c.142-2A>C), and RAB27A gene mutations (c.121delA/p.T41fs and c.272delA/p.D91fs). Among the 13 families undergoing prenatal diagnosis, genetic testing revealed that 11 fetuses carried wild-type genes, and these families elected to continue their pregnancies. One fetus exhibited identical genetic variants to the proband and received a clinical diagnosis consistent with the genetic disorder, while another fetus demonstrated chromosomal copy number variations. In both of these latter cases, the families opted for pregnancy termination. Conclusion:This study identified 11 unreported variants across seven genes, highlighting the need for further expansion of PID genetic variant databases.

To address the insufficiency of domestic small-dose Chinese herbal granule dispensing equipment,this study introduces the"black box method"design concept and,on this basis,designs a lightweight,compact and highly accurate dispensing device.This device uses a two-phase four-wire brushless motor to drive the slider for displacement,thereby controlling the volume of the medicine falling into the weighing device to complete the weighing of the medicine.Finally,a two-phase hybrid stepping motor is used to drive the weighing device to transfer the medicine.This paper first elaborates in detail on the mechanical structure and weighing dispensing principle of this device.Secondly,the ANSYS finite element software is used to conduct a force analysis test on the weighing device,and it is concluded that the deformation of the weighing device during the working process is 9.98×10-5 mm,and the maximum deformation of the discharge port is 6.65×10-5 mm.Finally,the ADAMS software is used to simulate and analyze the motion process of the mechanism.The results show that,under the premise of ensuring the accuracy of weighing,there are no virtual points or interference in the motion process.On this basis,a prototype test is conducted,and the error accuracy of the dispensing machine is about 0.066 g,which is higher than the traditional dispensing accuracy.This equipment has strong adaptability and high dispensing accuracy,providing a new solution for small-dose precise quantitative equipment.

To address the insufficiency of domestic small-dose Chinese herbal granule dispensing equipment,this study introduces the"black box method"design concept and,on this basis,designs a lightweight,compact and highly accurate dispensing device.This device uses a two-phase four-wire brushless motor to drive the slider for displacement,thereby controlling the volume of the medicine falling into the weighing device to complete the weighing of the medicine.Finally,a two-phase hybrid stepping motor is used to drive the weighing device to transfer the medicine.This paper first elaborates in detail on the mechanical structure and weighing dispensing principle of this device.Secondly,the ANSYS finite element software is used to conduct a force analysis test on the weighing device,and it is concluded that the deformation of the weighing device during the working process is 9.98×10-5 mm,and the maximum deformation of the discharge port is 6.65×10-5 mm.Finally,the ADAMS software is used to simulate and analyze the motion process of the mechanism.The results show that,under the premise of ensuring the accuracy of weighing,there are no virtual points or interference in the motion process.On this basis,a prototype test is conducted,and the error accuracy of the dispensing machine is about 0.066 g,which is higher than the traditional dispensing accuracy.This equipment has strong adaptability and high dispensing accuracy,providing a new solution for small-dose precise quantitative equipment.

Objective:To analyze the genetic variant characteristics of primary immunodeficiency diseases (PID) in families from Henan Province.Methods:This study conducted a retrospective analysis of 19 PID pedigrees referred to the Prenatal Diagnosis Center at Henan Provincial People's Hospital between January 2016 and March 2024. Among the 19 families, 13 underwent prenatal diagnosis at our hospital, while the remaining six received genetic counseling based on third-party genetic testing reports (confirmed by our institution's laboratory). The clinical data from these families were analyzed, and descriptive statistical analysis was applied to the data.Results:Among the 19 PID families, there were seven cases of combined immunodeficiency, three immunodeficiency syndromes, three phagocyte deficiencies, three antibody-dominant immunodeficiencies, and three immunodysregulatory disorders, involving a total of 12 genes ( IL2RG, ADA, RAG2, STAT3, SMARCAL1, ATM, POLA1, CYBB, BTK, RAB27A, LRBA, IL10R). A total of 25 genetic variants were identified, including 11 novel variants not previously documented in the ClinVar and HGMD professional databases. The novel variants comprised: IL2RG gene mutations (Exon5_8del and c.903_904delinsCT leading to p.E302*), ADA gene mutation (c.884A>G resulting in p.D295G), RAG2 gene mutation (c.513dupA causing p.W172Mfs3), POLA1 gene mutation (c.25+5G>C), CYBB gene mutations (c.824G>A/p.G275D and c.472A>T/p.K158), BTK gene mutations (c.522_523insC/p.A175fs and c.142-2A>C), and RAB27A gene mutations (c.121delA/p.T41fs and c.272delA/p.D91fs). Among the 13 families undergoing prenatal diagnosis, genetic testing revealed that 11 fetuses carried wild-type genes, and these families elected to continue their pregnancies. One fetus exhibited identical genetic variants to the proband and received a clinical diagnosis consistent with the genetic disorder, while another fetus demonstrated chromosomal copy number variations. In both of these latter cases, the families opted for pregnancy termination. Conclusion:This study identified 11 unreported variants across seven genes, highlighting the need for further expansion of PID genetic variant databases.