Objective:To explore the genetic basis of eighteen patients with tetrahydrobiopterin deficiency (BH4D) from Gansu Province.Methods:Eighteen patients diagnosed with BH4D at Gansu Provincial Maternal and Child Health Care Hospital from January 2018 to December 2021 were selected as the study subjects. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing.Results:All of the thirty-six alleles of the eighteen patients were successfully determined by molecular genetic testing. Sixteen patients were found to harbor variants of the PTS gene, and two had harbored variants of the QDPR gene. Ten variants were detected in the PTS gene, with the most common ones being c. 259C>T (34.38%) and c. 286G>A (15.63%). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 259C>T was classified as a pathogenic variant, whilst the c. 286G>A, c. 166G>A, c. 200C>T, c. 272A>G, c. 402A>C, c. 421G>T, c. 84-291A>G and c. 317C>T were classified as likely pathogenic variants. A novel c. 289_290insCTT variant was classified as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PP3+ PP4). The two variants (c.478C>T and c. 665C>T) detected in the QDPR gene were both classified as variants of uncertain significance (PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:Genetic testing has clarified the pathogenic variants in these BH4D patients, which has enabled timely and accurate clinical intervention and treatment, and provided a reference for genetic counseling and reproductive guidance for their families.

Objective To explore the medication rules and mechanism of action of traditional Chinese medicine compound patent formulas for vitiligo,and provide ideas for the development and the patent declaration work of new Chinese medicines for vitiligo.Methods China Patent Publication Bulletin website,National Knowledge Infrastructure Database,Patent Information Service Platform of China Intellectual Property Right Net(CNIPR),and Baiten Patent Platform were used to search for the patents of traditional Chinese medicine compound formulas for vitiligo from the establishment of the databases to 30th September,2023.Excel software and Traditional Chinese Medicine Inheritance Computing Platform(TCMICS V3.0)were used to establish a database of compound formulas,and carry out the statistics of frequency,association rules and clustering analysis of the formulas for internal and external prescriptions.The target and mechanism of action of the internal prescriptions of core high-frequency Traditional Chinese Medicine group for the treatment of vitiligo were further explored by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Symptom Mapping(Symmap),The Human Gene Database(Genecards),UniversalProtein(UniProt),STRING,Pharmaceutical DataBase(PDB)and other databases as well as software such as R Studio 4.2.2 and Cytoscape 3.9.1,and AutoDock Vina was used for molecular docking validation.Results The internal formulas included 335 patents and the external formulas included 189 patents.The rules of internal and external use are similar.The high-frequency traditional Chinese medicines are Tribuli Fructus,Psoraleae Fructus,Angelicae sinensis,Radix Polygoni Multiflori,Carthami Flos,Angelica dahurica,etc.;the key efficacies of the medicines are based on tonifying the deficiency,activating blood circulation and removing blood stasis;and the properties of the Chinese medicines are the nature of warmth,coldness and flatness,sweetness,bitterness,pungency and attribution to the liver,the spleen,the heart and the kidneys.Commonly used oral medicine pairs are Chuanxiong rhizome-Angelica,Astragalus-Angelica,etc.,high-frequency pairs of external medicines are Fructus mume-Psoraleae fructus,cuscuta-Psoraleae fructus,etc.;internal and external clustering of the core drugs are Psoraleae fructus,Tribuli Fructus,Angelica,Polygonum multiflorum,Angelica dahurica,Safflower,and other high-frequency medicines.The key targets of internal patents for the treatment of vitiligo are genes such as albumin,protein kinase B1,cystatinase 3,etc.The main active ingredients of the internal grouping for the treatment of vitiligo may be quercetin,kaempferol,luteolin,etc.,and the therapeutic mechanism may be related to the end products of glycosylation/receptor for glycosylation end products,tumour necrosis factor signalling pathway,phosphatidylinositol 3-kinase/protein kinase B and other signalling pathways,and involved in the process of blood lipids and atherosclerosis,human cytomegalovirus infection.The molecular docking results confirmed the docking activity of the herbal components with key receptor proteins.Conclusion This study reveals the similarity between the internal and external patented formulas of vitiligo in terms of medication,flavour,and meridian,suggesting that the pathways and indexes such as albumin,interleukin,and tumour necrosis factor of vitiligo patients can be improved by tonifying the liver and kidney,activating blood circulation and removing blood stasis,which also provides a reference for the research and development of new medicines for vitiligo,patent protection,and the use of clinical prescriptions.

Lung cancer is one of the malignant tumors with the highest incidence rate and mortality in the world today. Although significant progress has been made in the treatment of lung cancer, its 5-year survival rate is still very low. Ferroptosis is a cell death mode characterized by an increase in intracellular free iron, lipid peroxidation, and accumulation of reactive oxygen species. More and more evidence suggests that ferroptosis plays a crucial role in the occurrence and development of lung cancer, and exploring the mechanism of ferroptosis in lung cancer is of great significance for finding new diagnostic and treatment methods for lung cancer. This article reviews the regulatory mechanism of cell ferroptosis and its role in the occurrence and development of lung cancer, with the aim of providing new directions and ideas for the diagnosis and treatment of lung cancer.

To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.
Animals ; Bleomycin/pharmacology* ; Cytokines ; Drugs, Chinese Herbal ; Glutathione ; Idiopathic Pulmonary Fibrosis/drug therapy* ; Inflammation ; Lung/pathology* ; Male ; Network Pharmacology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase/metabolism* ; Transforming Growth Factor beta/pharmacology*

OBJECTIVE To investigate t he attitude of endocrinology physicians to clinical conversion and substitution of insulin drugs ，and to provide basis for improving the centralized procurement program of insulin. METHODS The proportion of convertible and substitutable insulin recognized by endocrinology physicians was investigated by questionnaire from 4 dimensions： intergenerational level ，bargaining group level ，common name level and brand/specification level. The subjects were endocrinology physicians in the third grade class A general hospitals in Nanchang. RESULTS A total of 89 questionnaires were successfully distributed，accounting for 80.2％ of the on-the-job endocrinology physicians （111 in total ）in the third grade class A general hospitals in Nanchang. Eighty-nine questionnaires were collected ，one of which was invalid ，and the effective rate was 98.9％. At the intergenerational level ，93.2％ of endocrinology physicians preferred insulin analogues. At the bargaining group level ，the weighted average of the convertible ratio between group 3 and group 4 approved by physicians was 63.9％. At the levels of common name and brand/specification ，the weighted averages of convertible proportion of each group were more than 70％. CONCLUSIONS The method of insulin grouping in Wuhan is reasonable which can complete clinical conversion and substitution of insulin in the group safely. It is suggested to cancel long-acting human insulin group. The weighted average of the proportion of convertible and substitutable drugs in the group is high. It is suggested to increase the agreed purchase volume of insulin and conduct“volume price linked ”negotiations. When the surveyed physicians choose the initial treatment scheme of insulin ，they pay more attention to the factors such as efficacy and safety ，so the replacement of insulin should be based on the clinical efficacy and drug safety.

Objective:To carry out genetic analysis for 3 children from two Chinese families affected with maple syrup urine disease (MSUD).Methods:Target capture - next-generation sequencing and Sanger sequencing were used to detect pathogenic variants associated with MSUD.Results:The proband from family 1 was found to harbor homozygous c. 560G>T (p.Gly187Val) variant of the BCKDHB gene (NM_000056), whilst the two patients from family 2 were found to harbor compound heterozygous variants c. 197-2A>G (splicing)/c.218delT (p.F74Sfs*4) of the BCKDHB gene. Among these, the c. 560G>T and c. 218delT variants were unreported previously. Conclusion:The new variants discovered in this study have expanded the mutational spectrum of the BCKDHB gene.

Objective:To investigate the pathogenic gene locus and prenatal genetic diagnosis of 54 families with oculocutaneous albinism (OCA).Methods:This retrospective study enrolled 54 OCA probands and their families from Gansu Province Maternal and Child Health Care Hospital from May 2014 to May 2020. TYR gene variation screening was performed on the probands by Sanger sequencing. Those with negative results were analyzed by high-throughput sequencing, and further verification was performed on their parents by Sanger sequencing. Among the 54 families, 15 ml amniotic fluid were collected from 16 women at 18-21 gestational weeks in their subsequent pregnancy. Sanger sequencing combined with short tandem repeats sequence for linkage analysis were performed for genetic analysis. All data were analyzed using descriptive statistical analysis. Results:Out of the 54 OCA probands, 48 were diagnosed as OCA1, five were OCA2 and one was OCA4 based on the Sanger sequencing and high-throughput sequencing detection. A total of 26 different variation sites were involved in the 48 OCA1 probands, including 15 missense mutations, five nonsense mutations, three splicing mutations, and three frame-shift mutations, among which, c.929insC (29%, 28/96) was the most frequent mutation, followed by c.896G>A (11%, 11/96), c.832C>T (8%, 8/96) and c.703T>C (5%, 5/96). The diagnosis was confirmed in all 16 fetuses in the 16 families that underwent prenatal diagnosis. Five of them were affected and their mothers chose to terminate the pregnancies, the other 11 pregnancies continued to delivery, including seven heterozygous carriers and four fetuses without the same pathogenic allele as the proband. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. All 11 children were in good health during telephone follow-up one month after birth. Postnatal validations were consistent with the prenatal tests.Conclusions:Genetic diagnosis could accurately identify various types of OCA and help to provide prenatal diagnosis and fertility consultation for subsequent pregnancies.

OBJECTIVE: To explore the genetic basis for a child with unexplained global developmental delay (GDD), seizure, and facial deformity. METHODS: Whole exome sequencing (WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of the patient and his parents. RESULTS: WES revealed that the patient has carried a previously unreported de novo heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene, Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.4906C>T variant of KMT2A gene was predicted to be pathogenic (PVS1+ PS2+ PM2+PP3). CONCLUSION The heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene probably underlay the disease in the child. Above finding has enriched the spectrum of pathogenic variants of the KMT2A gene.
Abnormalities, Multiple/genetics* ; Child ; Histone-Lysine N-Methyltransferase/genetics* ; Humans ; Intellectual Disability/genetics* ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Syndrome

Ferroptosis is an iron-dependent programmed cell death characterized by reactive oxygen species-induced lipid peroxide accumulation, which is different from cell apoptosis, pyroptosis, necrosis or autophagy. Ferroptosis plays an important role in the regulation of tumorigenesis and tumor development. Recent studies have shown that natural medicinal ingredients can induce ferroptosis in tumor cells through glutathione (GSH)/glutathione peroxidase 4 (GPx4) pathway, iron metabolism, lipid metabolism or other mechanisms. It has been reported that more than 30 natural medicinal ingredients can induce ferroptosis in tumor cells with multiple pathways and multiple targets. This article reviews the current research progress on the antitumor effects of natural medicinal ingredients through inducing cell ferroptosis.
Apoptosis ; Autophagy ; Ferroptosis ; Humans ; Neoplasms/drug therapy* ; Reactive Oxygen Species

To investigate the molecular mechanism of resveratrol inhibiting the metastasis of liver cancer . HepG2 and Huh7 cells were treated with different concentrations of resveratrol, and the cell viability was determined by CCK-8 assay to determine the optimal concentration of resveratrol for subsequent experiments. The expressions of miR-186-5p in liver cancer tissues and liver cancer cells were determined by quantitative real-time RT-PCR. The migration and invasion of HepG2 and Huh7 cells were detected by wound healing assay and Transwell assay, and the expression levels of epithelial-mesenchymal transition (EMT) related proteins were determined by Western blotting. Resveratrol with concentration of had no effect on the viability of HepG2 and Huh7 cells, so the concentration of resveratrol in subsequent experiments was 6.25 μmol/L. Resveratrol inhibited the wound healing and invasion of liver cancer cells; increased the expression of E-cadherin, and decreased the expression of vimentin and Twist1. The expression of miR-186-5p was significantly down-regulated in liver cancer tissues and cells compared with the adjacent tissues and normal liver cells (both <0.05). Furthermore, resveratrol induced the expression of miR-186-5p in liver cancer cells (both <0.01). Overexpression of miR-186-5p suppressed the migration, invasion and EMT of liver cancer cells. Knockdown of miR-186-5p blocked the inhibition effects of resveratrol on the migration, invasion and EMT of liver cancer cells. Resveratrol could inhibit the metastasis of liver cancer , which might be associated with up-regulating miR-186-5p.
Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation, Neoplastic ; Hep G2 Cells ; Humans ; Liver Neoplasms/genetics* ; MicroRNAs/genetics* ; Neoplasm Invasiveness/genetics* ; Resveratrol/pharmacology*