BACKGROUND:It is urgent to improve the study on the molecular mechanism of Ban's Culuan Zhuyun Decoction improving oocyte quality in polycystic ovary syndrome.OBJECTIVE:To observe the effects of Ban's Culuan Zhuyun Decoction on oocyte quality in a mouse model of polycystic ovary syndrome and to explore the underlying mechanisms of its intervention in polycystic ovary syndrome.METHODS:Subcutaneous injection of dehydroepiandrosterone sulfate was used to establish the polycystic ovary syndrome model in 21-day-old female Kunming mice,and the treatment was conducted for 21 consecutive days.The estrous cycle and pregnancy was recorded.ELISA was used to detect serum sex hormone levels.The rate of apoptosis in oocytes was detected using Annexin V staining.The level of reactive oxygen species in oocytes was detected using dichlorodihydrofluorescein diacetate.The condition of spindle bodies and chromosomes in oocytes were detected using the immunofluorescence method.Network pharmacology and molecular docking were used to verify the binding properties of Ban's Culuan Zhuyun Decoction core active components and oocyte maturation-related factors(growth differentiation factor 9 and bone morphogenetic protein 15).Real-time fluorescence quantitative PCR and western blot were used to detect the mRNA and protein expression levels of growth differentiation factor 9 and bone morphogenetic protein 15 in oocytes,respectively.RESULTS AND CONCLUSION:(1)Ban's Culuan Zhuyun Decoction core active components(quercetin,kaempferol,and β-sitosterol)showed good binding activities with growth differentiation factor 9 and bone morphogenetic protein 15.(2)Ban's Culuan Zhuyun Decoction ameliorated the estrous cycle,regulated serum hormone,increased the pregnancy,decreased the rate of apoptosis,declined the level of reactive oxygen species,diminished the rate of abnormal spindle assembly and chromosome loss(P<0.01,P<0.05);and promoted the mRNA and protein expression of growth differentiation factor 9 and bone morphogenetic protein 15(P<0.05).Therefore,Ban's Culuan Zhuyun Decoction may improve the oocyte quality and increase the fertility of polycystic ovary syndrome mice by regulating the gene expression of growth differentiation factor 9 and bone morphogenetic protein 15.

BACKGROUND:It is urgent to improve the study on the molecular mechanism of Ban's Culuan Zhuyun Decoction improving oocyte quality in polycystic ovary syndrome.OBJECTIVE:To observe the effects of Ban's Culuan Zhuyun Decoction on oocyte quality in a mouse model of polycystic ovary syndrome and to explore the underlying mechanisms of its intervention in polycystic ovary syndrome.METHODS:Subcutaneous injection of dehydroepiandrosterone sulfate was used to establish the polycystic ovary syndrome model in 21-day-old female Kunming mice,and the treatment was conducted for 21 consecutive days.The estrous cycle and pregnancy was recorded.ELISA was used to detect serum sex hormone levels.The rate of apoptosis in oocytes was detected using Annexin V staining.The level of reactive oxygen species in oocytes was detected using dichlorodihydrofluorescein diacetate.The condition of spindle bodies and chromosomes in oocytes were detected using the immunofluorescence method.Network pharmacology and molecular docking were used to verify the binding properties of Ban's Culuan Zhuyun Decoction core active components and oocyte maturation-related factors(growth differentiation factor 9 and bone morphogenetic protein 15).Real-time fluorescence quantitative PCR and western blot were used to detect the mRNA and protein expression levels of growth differentiation factor 9 and bone morphogenetic protein 15 in oocytes,respectively.RESULTS AND CONCLUSION:(1)Ban's Culuan Zhuyun Decoction core active components(quercetin,kaempferol,and β-sitosterol)showed good binding activities with growth differentiation factor 9 and bone morphogenetic protein 15.(2)Ban's Culuan Zhuyun Decoction ameliorated the estrous cycle,regulated serum hormone,increased the pregnancy,decreased the rate of apoptosis,declined the level of reactive oxygen species,diminished the rate of abnormal spindle assembly and chromosome loss(P<0.01,P<0.05);and promoted the mRNA and protein expression of growth differentiation factor 9 and bone morphogenetic protein 15(P<0.05).Therefore,Ban's Culuan Zhuyun Decoction may improve the oocyte quality and increase the fertility of polycystic ovary syndrome mice by regulating the gene expression of growth differentiation factor 9 and bone morphogenetic protein 15.

Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Objective:To explore the genetic basis of a child with mental retardation and developmental delay.Methods:A child who had attended the genetic clinic of Linyi People′s Hospital from October 2023 to April 2024 was selected as the study subject. Intelligence and development were assessed with simplified Peabody scale. Electroencephalogram and imaging data were collected. Peripheral blood samples of the child and her parents were collected for the screening of genetic metabolic diseases, chromosomal karyotyping, and trio-whole genome sequencing (trio-WGS) analysis. Candidate variant was verified by Sanger sequencing, and RNAseq was carried out to verify the alternative splicing due to the candidate variant. This study has been approved by the Medical Ethics Committee of Linyi People′s Hospital (No. YX200083).Results:The patient was an 8-year-and-11-month-old girl. Both of her parents had normal phenotypes. The child was assessed by the simplified Peabody scale as having intellectual disability and developmental delay. MRI showed no definite abnormal signals within the brain parenchyma, and electroencephalogram was normal. Screening of genetic metabolic diseases showed no obvious abnormality. Chromosomal karyotype was normal. Trio-WGS has detected a c. 697+ 1G>A variant in the intron 4 of the NFIX gene, along with 9 other variants within eight genes. The c. 697+ 1G>A variant may cause abnormal splicing of the NFIX gene transcript. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 697+ 1G>A variant was predicted to be pathogenic (PVS1+ PS2+ PM2_Supporting), while the evidence for pathogenicity of the other 9 variants was insufficient. Conclusion:The novel de novo c. 697+ 1G>A variant of the NFIX gene probably underlay the pathogenesis of the child, which may have caused the disease by leading to abnormal splicing.

Systematically combing the origin and characteristics of the classification style of contents in ancient traditional Chinese medicine （TCM） books through the ages， this article put forward that the emergence of the classification by category system for medical books in the Song Dynasty had become a reference for the classification medical book categories in later generations； under the influence of Neo Confucianism， the compilers of medical books in the Ming Dynasty applied the classification method of outline， which made the content of medical books well-organized and hierarchical， and according to the needs of systematic compilation of medical books and different compilation purposes， the classification logic of various medical books had been continuously improved， and breakthroughs had been made in the format， which improved perfecting the development of classification style in ancient comprehensive TCM books； the application of the body part classification method in the compilation of medical books in the Qing Dynasty made the classification of books more rigorous and organized， and the classification system of various medical texts became more mature. By systematically sorting out the characteristics and origins of the classification system of ancient TCM books throughout history is of great significance for comprehensively understanding of the development of ancient TCM books style and the promotion of the collation， protection and use of ancient books.

Brain aging is closely related to cognitive decline,neurodegenerative diseases,and vascular dementia.Hydrogen sulfide(H2S)can delay brain aging by regulating protein homeostasis,anti-oxidative stress,inhibiting inflammation,reducing brain cell apoptosis and improving microcirculation.

Chagas disease (also known as American trypanosomiasis) is a zoonotic disease caused by Trypanosoma cruzi. It has a long incubation period and low diagnosis rate. At present, there is no vaccine to prevent it, and there is no specific drug at the late stage of the disease. Therefore, some scholars call it "new AIDS". In the past two decades, Chagas disease has spread from the main epidemic area of Latin America to other non-epidemic countries. At the same time, Triatoma rubrofasciata, one of its main vectors, is widely distributed in the world, including some humid and warm southern areas of China. Therefore, in this paper, the distribution characteristics, biology and molecular biology of Triatoma rubrofasciata are comprehensively reviewed, in order to provide reference for the prevention and control of imported Chagas disease in China.

Chimeric antigen receptor T cell(CAR-T)therapy has produced remarkable results in the treatment of hematological tumors.The BCMA antigen is widely expressed on the surface of multiple myeloma cells and is a suitable,efficient target for CAR-T therapy.BCMA CAR-T cell therapy has a high response rate for relapsed or refractory patients in particular,and CAR-T cells are still detectable in most patients 1 year after infusion.However,drug resistance and disease recurrence remain key problems in clinical management.In this paper,we discuss the response factors and resistance induction mechanism of BCMA CAR-T cell therapy from several perspectives,such as the immune es-cape of multiple myeloma cells,CAR-T product factors,previous treatment regimens,and tumor immune microenvironment inhibition.We also propose possible optimization strategies in order to provide reference for future exploration.

【Objective】 To evaluate the efficacy and safety of human coagulation factor Ⅷ developed by Shenzhen Weiguang Biological products Co, Ltd in the treatment of patients with hemophilia A. 【Methods】 A prospective, multi-center, open, single-group clinical study was conducted. A total of 65 subjects with hemophilia A were enrolled, and human coagulation factor Ⅷ(FⅧ) was injected according to the patients’ bleeding severity. The improvement score of bleeding symptoms and signs after the first infusion of the first bleeding event and the transfusion efficiency of FⅧ activity at 10 min and 1 hour after infusion were taken as the main efficacy indexes. The improvement scores of bleeding symptoms and signs after the first infusion and the increase of FⅧ activity at 10 min and 1 hour after infusion were the secondary efficacy indexes. 【Results】 The 65 subjects were enrolled in safety analysis set (SS) and full analysis set (FAS), and 58 of them were enrolled in protocol analysis set (PPS). Ten minutes and one hour after the first infusion, the level of factor Ⅷ activity in the subjects increased significantly, and the FⅧ activity increased by 100% or more in more than 79% of the subjects. The average infusion efficiency of FⅧ activity in all subjects was more than 100%. In 70% of the subjects, the pain was relieved rapidly and /or the bleeding symptoms were significantly improved 8 hours after each bleeding infusion, and the improvement rate of bleeding symptoms and signs reached 100% 72 hours after infusion. 【Conclusion】 After infusion of human coagulation factor Ⅷ, the activity level of factor Ⅷ in patients with hemophilia A significantly increased. The infusion efficiency can reach a optimal level, and the bleeding symptoms can be significantly improved.

【Objective】 To evaluate the clinical efficacy and safety of one kind of human prothrombin complex concentrate in treatment of patients with hemophilia B. 【Methods】 The clinical data of 36 patients with hemophilia B treated with human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. from May 2018 to April 2019 were retrospectively analyzed, and its clinical efficacy and safety were analyzed. 【Results】 A total of 35 subjects entered the full analysis set (FAS)and safety set (SS), 33 subjects entered the per protocol Set (PPS). Thirty minutes after the first infusion of FAS subjects, the activity of coagulation factor Ⅸ increased from (3.93±0.975) IU/dL to (25.61±9.337) IU/dL, and the infusion efficiency was (96.43±22.007)%. The increased value of coagulation factor Ⅱ activity was (73.25±14.874) IU/dL. The activity of coagulation factor Ⅶ was (42.79±16.847) IU/dL. The increased value of coagulation factor Ⅹ activity was (65.29±17.042) IU/dL. The increased value of coagulation factor Ⅸ activity was (21.68±9.434%) IU/dL. Twenty-four hours after the first infusion of FAS subjects, the improvement of bleeding symptoms and signs was excellent in 21 cases (60%), improved in 14 cases (40.0%), and the effective rate was 100%. The incidence of adverse reactions was 2.9%(1/35), and there was no antibody to human coagulation factor Ⅸ and new virus infection. 【Conclusion】 Infusion of human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. in the treatment of hemophilia B has significant clinical efficacy and good safety.