OBJECTIVE: To analyze the incidence of abnormal hemoglobin (Hb) in neonates in Guangzhou area, as well as the results of quantitative analysis of Hb in neonatal umbilical cord blood and genetic diagnosis of thalassemia in neonates with abnormal Hb; And to explore the hematological phenotypes and clinical characteristics of neonates with abnormal Hb and their parents, providing a reference for eugenics and childcare. METHODS: 650 neonates born at Guangdong Provincial People's Hospital who underwent Hb electrophoresis were included in this study. The results of routine blood test of umbilical cord blood , Hb electrophoresis and α-, β-thalassemia gene detection of the neonates were collected. The genotype distribution of thalassemia in the neonates was analyzed. Additionally, the abnormal Hb content of α and β variants was studied. Furthermore, the differences in hematological parameters between abnormal Hb neonates and normal neonates and α-thalassemia neonates, as well as between the parents of abnormal Hb neonates and normal adults were compared. RESULTS: Among the 650 neonates, 332 (51.08%) were diagnosed with thalassemia, including 235 cases of α-thalassemia (36.15%), 79 cases of β-thalassemia (12.15%), and 18 cases of compound αβ-thalassemia (2.77%). Among all the α-thalassemia genotypes, the most prevalent one was -- ^SEA/αα (48.94%), followed by -α^3.7/αα (20.00%), -α^4.2/αα (11.06%), and αα^CS/αα (8.94%). The four most common genotypes of β-thalassemia were β^CD41-42 (32.91%), β^IVS-Ⅱ-654 (26.58%), β^-28 (21.52%), and β^E (10.13%), respectively. 275 cases of abnormal bands were found in Hb electrophoresis of umbilical cord blood, with a detection rate of 42.31%. The abnormal Hb content of α-variant in the neonates was significantly higher than that of β-variant (P < 0.001). The levels of Hb, MCV, MCH, Hb A, and Hb F in neonates with abnormal Hb were lower than those in normal neonates, while the RDW-CV was higher than that in normal neonates, with statistical significantce (P < 0.05). The levels of RBC and Hb A in neonates with abnormal Hb were lower than those in neonates with α-thalassemia, while the level of MCH was higher than that in neonats with α-thalassemia, with statistical significance (P < 0.05). The levels of Hb, MCV, MCH, and Hb A in parents of neonates with abnormal Hb were lower than those in normal adults, while the RDW-CV was higher than that in normal adults, and the differences were statistically significant (P < 0.05). CONCLUSION The abnormal Hb content of α-variant in the neonates is significantly higher than that of β-variant in the neonates in Guangzhou, which can help to presume whether it is α chain or β chain based on the abnormal Hb content, providing a reference for globin gene sequencing. Meanwhile, analysis of various hematological screening-related indicators in neonates in the early stage is beneficial for early warning of the occurrence of abnormal Hb combined with thalassemia, reducing missed diagnoses to a certain extent.
Humans ; Infant, Newborn ; Genotype ; Hemoglobins, Abnormal/genetics* ; China/epidemiology* ; alpha-Thalassemia/epidemiology* ; beta-Thalassemia/genetics* ; Parents ; Female ; Male ; Fetal Blood

Isocitrate dehydrogenase 1 (IDH1) R132H is the most common mutated gene in grade II-III gliomas and oligodendrogliomas. Instead of activating telomerase (a reverse transcriptase which using RNA as a template to extend telomere length), the majority of IDH1^R132H mutant glioma maintain telomere length through an alternative mechanism that relies on homologous recombination (HR), which is known as alterative lengthening of telomere (ALT).The phenotype of ALT mechanism include: ALT associated promyelocytic leukemia protein (PML) bodies (APBs); extrachromosomal telomeric DNA repeats such as C- and T-loops; telomeric sister chromatid exchange (T-SCE), etc. The mechanism of ALT activation is not fully understood. Recent studies have shown that mutation IDH1 contributes to ALT phenotype in glioma cells in at least three key ways. Firstly, the IDH1^R132H mutation mediates RAP1 down-regulation leading to telomere dysfunction, thus ensuring persistent endogenous telomeric DNA damage, which is important for ALT activation. Spontaneous DNA damage at telomeres may provide a substrate for mutation break-induced replication (BIR)‑mediated ALT telomere lengthening, and it has been demonstrated that RAP1 inhibits telomeric repeat-containing RNA, transcribed from telomeric DNA repeat sequences (TERRA) transcription to down-regulate ALT telomere DNA replication stress and telomeric DNA damage, thereby inhibiting ALT telomere synthesis. Similarly, in ALT cells, knockdown of telomere-specific RNaseH1 nuclease triggers TERRA accumulation, which leads to increased replication pressure. Overexpression of RNaseH1, on the other hand, attenuates the recombination capacity of ALT telomeres, leading to telomere depletion, suggesting that RAP1 can regulate the level of replication pressure and thus ALT activity by controlling TERRA expression. Secondly, the IDH1^R132H also alters the preference of the telomere damage repair pathway by down-regulating XRCC1, which inhibits the alternative non-homologous end joining (A-NHEJ) pathway at telomeres and alters cellular preference for the HR pathway to promote ALT. Finally, the IDH1^R132H has a decreased affinity for isocitric acid and NADP+ and an increased affinity for α ketoglutarate (α‑KG) and NADPH, so that the mutant IDH1^R132H catalyzes the hydrogenation of α‑KG to produce 2-hydroxyglutarate (2-HG)in a NADPH-dependent manner. Because 2-HG is structurally similar to α‑KG, which maintains the trimethylation level of H3k9me3 by competitively inhibiting the activity of the α‑KG-dependent histone demethylase KDM4B, and recruits heterochromatin protein HP1α to heterochromatinize telomeres, and promote ALT phenotypes in cooperation with the inactivating of ATRX. In addition, it has been shown that APBs contain telomeric chromatin, which is essentially heterochromatin, and HP1α is directly involved in the formation of APBs. Based on these studies, this article reviews the mechanism of IDH1^R132H mediated telomere dysfunction and the preference of DNA repair pathway at telomeres in cooperate with ATRX loss to promote ALT, which may provide references for clinical targeted therapy of IDH1^R132H mutant glioma.

Objective:To summarize the research on oral health education for pregnant women.Methods:The literature was described and analyzed using a scoping review method. Seven databases, such as PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and WanFang Data, were electronically searched, and the search period was from database establishment to October 30, 2023.Results:A total of 43 articles were included. The implementers of health education were mainly dental professionals and prenatal healthcare personnel. The theoretical basis included the health belief model, planned behavior theory, social cognitive model and so on. The methods involved traditional teaching or lectures, family-centered, internet-based, and motivational interviews. The contents contained many aspects of oral health for pregnant women. The evaluation indicators mainly covered oral health knowledge, attitude and practice, and self-efficacy, oral health beliefs, oral health status, the incidence of oral diseases, adverse pregnancy outcomes of pregnant and postpartum women, and childhood caries incidence.Conclusions:We should establish a cooperation team of the Department of Stomatology and Obstetrics and Gynecology, incorporate oral health for pregnant women into prenatal care projects, fully utilize the platform of pregnant women's schools, explore the optimal theoretical basis for oral health education, and improve the content of oral health education for pregnant women.

The fundamental principle of traditional Chinese medicine(TCM) is holism, and it is crucial for TCM to address the key issue of the "holistic view" of Chinese herbal medicine. While the overall regulatory effects of Chinese herbal medicine have been widely recognized, the holistic internal logic of individual ingredients of Chinese herbal medicines require further clarification. In order to comprehensively understand the mechanism of action of Chinese herbal medicine, this paper combined the holistic view of Chinese herbal medicine with differentiation thinking to explore the intrinsic logical relationships within Chinese herbal medicine. Starting from the perspective of the coexistence of multiple components in Chinese herbal medicine, this paper systematically examined the "self-consistent" phenomenon within single Chinese herbal medicine. This phenomenon refers to the consistent or opposing actions of various components in terms of their physical and chemical properties, pharmacokinetic effects, biological effects, flavors and properties, and TCM efficacy. The paper summarized various logical relationships of syndrome differentiation exhibited by the same Chinese herbal medicine, analyzed the underlying reasons, and focused on analyzing external factors affecting the "self-consistent" phenomenon in the efficacy of Chinese herbal medicine, aiming to better elucidate the theoretical basis of the pharmacological effects of Chinese herbal medicine, further enrich the scientific connotation of the holistic view of Chinese herbal medicine, and provide theoretical guidance for the preparation process, compatibility patterns, and formulation design of Chinese herbal medicine.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

BACKGROUND: Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown. METHODS: In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot. RESULTS: The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC. CONCLUSIONS These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.

Aim To establish the 3D hepatocyte model by selecting the humanized hepatocyte HepG2 cells and 3D cell culture methods, and to establish the 3D hepatocyte cytokinesis-block micronucleus cytome(CBMN-cyt)assay and 3D hepatocyte comet assay by using chemicals of different mode of action.Methods In this study, a scaffold-free culture method was used to successfully establish a 3D HepG2 hepatocyte spheroid model.The appearance of the sphere, the survival rate of cells inside the sphere, the gene expression of phase I and II metabolic enzymes, and the expression of liver-specific biomarkers were selected as the observation indicators to obtain the best culture conditions for the 3D hepatocyte model.The 3D hepatocyte model was combined with in vitro micronucleomics test and in vitro comet test to explore its applicability for genotoxicity test.Results The best culture conditions for the 3D hepatocyte model was 5×103 cells/20 μL /drop inoculation, cultivating for seven days.A 3D hepatocyte CBMN-cyt assay was established using mitomycin C(MMC), a micronucleus positive compound, and the results showed that it could successfully detect the genotoxicity and cytotoxicity of MMC.Compared with the CBMN-cyt results of 2D hepatocyte model, 3D hepatocyte model had higher sensitivity in detecting MN and Nbud.The 3D hepatocyte comet assay methods were established using the known in vivo and in vitro comet assay positive compound methyl methanesulfonate(MMS), and the results showed that MMS could significantly increase the tail DNA% of 3D hepatocytes with low cytotoxicity.The sensitivity of 3D hepatocyte model to MMS genotoxicity detection was higher than that of 2D cells.Conclusions The 3D hepatocyte model established in this study is easy to use and low in cost, and shows good sensitivity and specificity in the in vitro micronucleus test and comet test, suggesting that the 3D hepatocyte genotoxicity test method is used in early drug genotoxicity screening.It has good application prospects in additional experimental research.

Astragali Radix, a medicinal herb for invigorating Qi, has anti-aging, anti-tumor, immunoregulatory, blood sugar-and lipid-lowering, anti-fibrosis, anti-radiation and other pharmacological effects. This article reviewed the studies about the chemical components and pharmacological effects of Astragali Radix. According to the theory of quality markers(Q-markers) of Chinese medicinal materials, we predicted the Q-markers of Astragali Radix from traditional efficacy, chemical component validity, measurability, plant phylogeny, and pharmacokinetis. The results showed that total polysaccharides, flavonoids(e.g., calycosin-7-O-β-D-glucoside, formononetin, calycosin, quercetin, and ononin), and saponins(e.g., astragalosides Ⅱ, Ⅲ, and Ⅳ) can be taken as the main Q-markers. This review lays a foundation for regulating the quality research and standard establishment of Astragali Radix, and benefits the control and quality supervision of the production process of Astragali Radix and its related products.
Astragalus Plant ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/pharmacology* ; Flavonoids ; Plant Roots

In traditional oral practice, the presystemic interactions with gut microbiota is an important mechanism underlying the holistic health benefits of Chinese herbal medicines (CHMs), making the study of CHMs distinct from the research of Western medicines of which the systemic exposure (level in blood) is the starting point and the core. Gut microbial metabolism complements host metabolism in maintaining metabolic homeostasis of many biologically important endogenous molecules and the disposition of numerous exogenous compounds. Among them, the widely distributed gut bacterial β-glucuronidases (BGUSs) coordinate with host UDP-glucuronosyltransferases (UGTs) to play a role in the occurrence and intervention of diseases by affecting the glucuronidation homeostasis and altering the intestinal local and/or systemic exposure of endogenous compounds and xenobiotics. On one hand, many ingredients of CHMs undergo enterohepatic circulation; On the other hand, CHMs can act on BGUSs directly or indirectly change the distribution and function of BGUSs through reprogramming gut microbiome. The multiple interactions between BGUSs and CHMs may play an important role in the overall therapeutic benefits of CHMs. This work firstly summarizes the latest research progress on BGUSs; then the physiological, pathological and pharmacological significance of BGUSs are exemplified with representative endogenous and exogenous compounds from the aspects of nutrient utilization, metabolic homeostasis, and therapeutic response based on the varied substrate spectra of BGUSs; finally, the scattered data in literature were integrated to summarize the multiple interactions between BGUSs and CHMs, highlighting the important role of BGUSs in the holistic actions of CHMs.