Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.
Rats ; Mice ; Animals ; Matrix Metalloproteinase 9/metabolism* ; Rats, Sprague-Dawley ; Neuroinflammatory Diseases ; Interleukin-1beta/metabolism* ; Spinal Cord/metabolism* ; Signal Transduction ; Hyperalgesia/metabolism* ; Neuralgia/metabolism*

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal

OBJECTIVE To study the improvement effect and mechanism of Gubenanshen decoction on menopausal syndrome model rats . METHODS Totally 70 rats were anesthetized and placed on the operating table for bilateral ovariectomy to induce menopausal syndrome model . Other 10 rats without modeling were taken as sham operation group . Sixty model rats were divided into model group ，Gengniananpian group （TCM positive control group ，0.56 g/kg），Estradiol valerate tablet group （chemical drug positive control group ，0.1 mg/kg），Gubenanshen decoction high -dose，medium-dose and low -dose groups （18.0，9.0，4.5 g/kg）， with 10 rats in each group . Model group and sham operation group were given normal saline intragastrically ；administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 4 weeks. After last administration ，the plasma contents of luteinizing hormone （LH），follicle stimulating growth hormone （FSH）and estradiol （E2）were determined .The indexes of uterus，adrenal gland ，spleen and thymus were measured ；pathological changes of rat uterus were observed ；mRNA expressions of kisspenptin 1（Kiss-1），inositol triphosphate receptor 1（IP3R1）and gonadotropin -releasing hormone （GnRH）in hypothalamic tissues were detected ，and the protein expressions of Kiss -1，ERK1/2 and p -ERK1/2 were also detected . RESULTS Compared with sham operation group ，the contents of LH and FSH in the plasma of rats were significantly increased in model group （P＜0.05 or P＜0.01）. The contents of E 2，organ index ，mRNA expressions of Kiss -1，IP3R1 and GnRH and protein expressions of Kiss -1 and p-ERK1/2 were decreased significantly in hypothalamic tissues （P＜0.05 or P＜0.01）. The glands of the uterus were reduced and the cells in the lamina propria were dense . Compared with model group ，above indexes of Gubenanshen decoction groups （except for the content of E 2 in the low -dose group ）were reversed significantly （P＜0.05 or P＜0.01）. The number of uterine glands increased，and single columnar epithelial cells were arranged orderly （except for the low -dose group ）. CONCLUSIONS Gubenanshen decoction can increase mRNA expressions of Kiss -1，IP3R and GnRH and protein expressions of Kiss -1 and p -ERK1/2 in hypothalamic tissues of rats ，and activate GnRH secretion signaling pathways so as to improve the menopausal syndrome .

Phenolic compounds are widely found in natural Chinese medicinal plants and have excellent pharmacological properties, such as antioxidation and anti-inflammation. They are the main pharmacological components of many medicinal Chinese herbs. Oral microbiota, especially its composition and metabolism, is highly related to the balance of oral microecology and plays a key role in the occurrence and development of oral diseases. Recent studies have shown that phenolic compounds of traditional Chinese herbs can prevent and treat oral diseases, such as caries, periodontal disease, and oral mucosal infection, by regulating the composition, metabolites, and virulence of oral microorganisms. This review will summarize and discuss the regulation of phenolic compounds on oral microbes.
Antioxidants ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Phenols ; Plants, Medicinal

Next-generation sequencing has allowed identification of millions of somatic mutations in human cancer cells. A key challenge in interpreting cancer genomes is to distinguish drivers of cancer development among available genetic mutations. To address this issue, we present the first web-based application, consensus cancer driver gene caller (C), to identify the consensus driver genes using six different complementary strategies, i.e., frequency-based, machine learning-based, functional bias-based, clustering-based, statistics model-based, and network-based strategies. This application allows users to specify customized operations when calling driver genes, and provides solid statistical evaluations and interpretable visualizations on the integration results. C is implemented in Python and is freely available for public use at http://drivergene.rwebox.com/c3.

BACKGROUND: Bone morphogenetic protein 2 (BMP-2) has a strong ability to induce and promote the osteogenic differentiation of mesenchymal stem cells. OBJECTIVE: To evaluate the BMP-2 effect on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on an injectable nano-hydroxyapatite/chitosan (nHA/CS) composite scaffold. METHODS: (1) Experiment 1: Passage 3 BMSCs were divided into two groups and cultured with the nHA/CS scaffold or cultured alone. Cell counting kit-8 was used to detect cell proliferation at 1, 3, 5, 7, 14 days of culture. (2) Experiment 2: Passage 3 BMSCs were seeded onto the nHA/CS scaffold and cultured in culture medium containing BMP-2 or not. Alkaline phosphatase activity in cells was detected at 3, 6, 9, 12, 15 days of culture. Cell counting kit-8 was used to detect cell proliferation at 1, 3, 5, 7, 14 days of culture. Alizarin red staining was used to observe the osteogenic differentiation of cells at 1 and 2 weeks of culture. RESULTS AND CONCLUSION: (1) Experiment 1: With the prolongation of culture time, the absorbance values in the two groups were gradually increased, but there was no significant difference between the two groups. At 7 days of culture, the BMSCs adhered tightly to the scaffold surface. (2) Experiment 2: With the prolongation of culture time, the alkaline phosphatase activities in the two groups were gradually increased, and moreover, the alkaline phosphatase activity in the experimental group was higher than that in the control group at different culture time (P < 0.05). The absorbance values in the two groups were also gradually increased, and the value in the experimental group was higher than that in the control group at different culture time (P < 0.05). At 1 and 2 weeks of culture, the number of calcified nodules was higher in the experimental group than the control group. To conclude, BMP-2 has a promotion role in the proliferation and differentiation of BMSCs cultured on the injectable nHA/CS scaffold.