Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

The prevalence of diabetes in China is increasing year by year， and has become a health issue of close concern to the whole society. Glucagon-like peptide-1 （GLP-1） receptor agonist （GLP-1RA）， as a new class of glucose-lowering drugs， is now widely used in the treatment of type 2 diabetes mellitus （T2DM） because of its significant glucose-lowering efficacy and low risk of hypoglycemia. As the level of evidence for its effects on improving cardiovascular system and renal protection and reducing body mass continues to improve， its status in the treatment guidelines for T2DM is gradually increasing. Currently， nine GLP-1RA drugs have been approved for the clinical treatment of T2DM in China. Although all of these drugs exert hypoglycemic effects based on the activation of GLP-1 receptors in the body， the differences in their own structures and natural GLP-1 amino acid homology lead to large differences in pharmacokinetic parameters and clinical efficacy among different analogs. In order to enable clinicians and pharmacists to have a full understanding of the characteristics and clinical evidence of these analogs and to better perform their therapeutic effects， Liaoning Provincial Pharmaceutical Society organized clinical medicine and pharmacy experts to develop a medication guide for nine GLP-1RA drugs to provide a reference for clinical medication needs and promote rational and standardized use by compiling and summarizing the pharmacological characteristics， clinical applications， adverse reactions， interactions， the medications in special populations and medication management.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective: This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease (CKD) in Shanghai community residents. Methods: We used data from a cohort study of community residents who participated in three examinations in 2008, 2009, and 2013, respectively. Fasting plasma glucose (FPG) level, blood pressure (BP), and lipid levels were determined in 2,109 participants at all three visits, and CKD was evaluated between the second and the third visits. Visit-to-visit variabilities in metabolic factors were described by coefficients of variation (CV) at three visits. A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV. CKD was defined as the estimated glomerular filtration rate < 60 mL/min per 1.73 m Results: A total of 200 (9.5%) participants had CKD at the third visit. Compared with the lowest quartile of CV, the highest quartile was associated with a 70% increased risk of CKD for FPG [odds ratio, Conclusion The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.
Aged ; Aged, 80 and over ; China/epidemiology* ; Cohort Studies ; Female ; Glomerular Filtration Rate ; Humans ; Incidence ; Male ; Middle Aged ; Renal Insufficiency, Chronic/physiopathology*

Objective To investigate the clinical efficacy of electroacupuncture and (or) massotherapy plus behavior therapy for cervical spondylosis.Methods Three hundred patients with cervical spondylosis were randomly allocated to three groups (A, B and C) by random number generated from calculator, 100 cases each. In addition to cupping and behavior therapy, group A received electroacupuncture; group B, massotherapy; group C, electroacupuncture and massotherapy. The clinical symptom and sign score was recorded in the three groups before and after treatment. The clinical therapeutic effects were compared.Results There were no statistically significant differences in the clinical control rate, marked control rate and total efficacy rate among the three groups after four and eight weeks of treatment and at the 4-month and 6-month follow-ups after treatment (P>0.05). In the three groups, there was a statistically significant difference in the clinical symptom and sign score between before treatment and after four and eight weeks of treatment or at the 4-month and 6-month follow-ups after treatment (P<0.01) and between after four weeks of treatment and after eight weeks of treatment or at the 4-month and 6-month follow-ups after treatment (P<0.01). There was no statistically significant differences in the clinical symptom and sign score among the three groups after four and eight weeks of treatment and at the 4-month and 6-month follow-ups after treatment (P>0.05). Conclusions Electroacupuncture and (or) massotherapy plus behavior therapy is an effective protocol for preventing and treating cervical spondylosis. It is characterized by simplicity, convenience, easiness and cheapness and can be provide for clinical application.

The BCCIP (BRCA2- and CDKN1A-interacting protein) is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCCIP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and colorectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 subunits catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCCIP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence. Gene expression studies combined with siRNA knockdown data locked candidate genes including BCCIP of the INO80/YY1 complex. Silencing or over-expressing the subunits of the INO80/YY1 complex regulates the expression level of BCCIP both in mRNA and proteins in cells. Also, the functions of INO80/YY1 complex in regulating the transactivation of BCCIP were confirmed by luciferase reporter assays. Chromatin immunoprecipitation (ChIP) experiments clarify the enrichment of INO80 and YY1 at +0.17 kb downstream of the BCCIP transcriptional start site. However, this enrichment is significantly inhibited by either knocking down INO80 or YY1, suggesting the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCCIP promoter region. Our findings strongly indicate that BCCIP is a potential target gene of the INO80/YY1 complex.
Calcium-Binding Proteins ; genetics ; metabolism ; Cell Cycle Proteins ; genetics ; metabolism ; Chromatin Assembly and Disassembly ; physiology ; DNA Helicases ; genetics ; metabolism ; HeLa Cells ; Humans ; Multiprotein Complexes ; genetics ; metabolism ; Nuclear Proteins ; genetics ; metabolism ; Promoter Regions, Genetic ; physiology ; Transcription, Genetic ; physiology ; YY1 Transcription Factor ; genetics ; metabolism

OBJECTIVETo study the molecular mechanisms of protein C (PC) deficiency caused by PC gene mutations of C64W, F139V and K150 deletion (K150d).

METHODSWild-type and mutant PC cDNA expression plasmids (PCwt, PC C64W, PC F139V, PC K150d) were constructed and transfected into COS-7 cells or CHO cells respectively for in vitro expression study and immunofluorescent assay. Fluorescent real-time PCR was used to detect the expression of PC mRNA, protein degradation inhibition and endo-beta-N-acetylglucosaminidase H (Endo H) digestion experiments to explain the mutant protein degradation pathway and its localizations inside the cells.

RESULTSPC C64W was not secreted from the cells and was gradually degraded inside the cells. There was partial secretion of PC F139V, most of the protein molecule was not secreted and degraded intracellularly. Mutant PC K150d was secreted normally from the cells. Fluorescent realtime PCR analysis of total mRNA from transfected cells showed no reduction of the mutant PC mRNA expression compared with that of wild-type PC mRNA. Protein degradation inhibition experiments showed that mutants PC C64W and PC F139V were degraded intracellularly through the proteasome pathway. Endo H digestion experiments and immunofluorescence results suggested that mutant PC molecules were located mainly in pre-Golgi apparatus.

CONCLUSIONSImpaired secretion and degradation intracellularly of the mutants might be the molecular mechanisms of PC deficiency caused by C64W and F139V mutations. K150 deletion mutation might not affect the secretion of the mutant.

Animals ; CHO Cells ; COS Cells ; Cercopithecus aethiops ; Cricetinae ; Cricetulus ; Humans ; Mutation ; Plasmids ; genetics ; Protein C ; genetics ; Protein C Deficiency ; genetics ; Transfection

OBJECTIVETo identify the phenotype and gene mutation in two Chinese pedigrees with hereditary protein C deficiency.

METHODSThe plasma level of protein C activity (PC: A) , protein C antigen (PC: Ag), protein S activity (PS: A), and antithrombin activity (AT: A) of the probands and their family members were detected using chromogenic assay and ELISA, respectively. All of the nine exons and intron-exon boundaries of protein C gene were amplified by PCR and analyzed by direct sequencing of the probands. Restriction enzyme site analysis was used to confirm the mutation.

RESULTSThe plasma PC: A and PC: Ag for proband 1 was 1.2% and 0, respectively. Compound heterozygous mutations, C(TGC)64W (TGG) and F(TTC) 139V(GTC) , were identified in her, the former being inherited from the maternal side and the later the paternal side. Further genetic analysis showed that her husband ( II 8) had the heterozygous deletion mutation (K150 or 151 Del) in exon 7, her daughter had the same heterozygous deletion mutation and a F139V. The plasma PC: A and PC: Ag for proband 2 was 50. 3% and 1.9 mg/L, respectively. He had the heterozygous Lys150 or Lys151 deletion mutation, which was inherited from his father. Polymorphisms of C/T at position - 1654, A/G at - 1641 , and A/T at - 1476A/T in the promoter region of protein C were confirmed in all members of the two pedigrees, of which, proband 2 had homozygous CC/GG/TT. The F139V mutation was confirmed by restriction enzyme site analysis and polymorphism for this mutation was excluded. PS: A and AT: A were in normal range for all members.

CONCLUSIONCompound heterozygous mutation C64W and F139V of protein C gene lead to type I hereditary protein C deficiency for proband 1. K150 or 151 deletion mutation and polymorphism of CC/GG/TT might lead to type I hereditary protein C deficiency for proband 2. C64W is a novel mutation for protein C gene. F139V and K150 or 151 deletion mutation are reported for the first time in China.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Genotype ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Polymorphism, Genetic ; Protein C Deficiency ; genetics

Objective To design and clone all known and predicted coding genes of Epstein-Barr virus (EBV) as the cDNA probes for preparing the microarray for EBV detection, thereby to facilitate further investigation of the pathogenetic role of EBV. Methods Oligo 6.0 software, BLAST program and Primer Premier 5 software were employed to design and screen the cDNA probes of the whole EBV genome, whose length ranged from 300 to 600 mer each with high specificity. These cDNA probes obtained through PCR and reverse transcriptase (RT)-PCR amplification from the genomic DNA and RNA of B95-8 cells and nasopharyngeal carcinoma (NPC) tissue were cloned into T/A clone vector, followed by identification of these probes by sequencing analysis. Result and Conclusion A total of 85 gene fragments (BWRF1 genecontained 7 repeats of open reading frames) coding for proteins and 2 EBERs in EBV genome were successfully cloned, not including LF1 and LF3 genes that did not exist in EBV genome ofB95-8 cells, which provides the basis for preparing microarray to explore the role of EBV genome in its related diseases.

Objective To design and clone all known and predicted coding genes of Epstein-Barr virus (EBV) as the cDNA probes for preparing the microarray for EBV detection, thereby to facilitate further investigation of the pathogenetic role of EBV. Methods Oligo 6.0 software, BLAST program and Primer Premier 5 software were employed to design and screen the cDNA probes of the whole EBV genome, whose length ranged from 300 to 600 mer each with high specificity. These cDNA probes obtained through PCR and reverse transcriptase (RT)-PCR amplification from the genomic DNA and RNA of B95-8 cells and nasopharyngeal carcinoma (NPC) tissue were cloned into T/A clone vector, followed by identification of these probes by sequencing analysis. Result and Conclusion A total of 85 gene fragments (BWRF1 genecontained 7 repeats of open reading frames) coding for proteins and 2 EBERs in EBV genome were successfully cloned, not including LF1 and LF3 genes that did not exist in EBV genome ofB95-8 cells, which provides the basis for preparing microarray to explore the role of EBV genome in its related diseases.