BACKGROUND: The decrease of activity level of choline acetyltransferase (ChAT) and reduction of membrane protein of synaptic vesicles are the main biochemical indexes in Alzheimer disease. Traditional Chinese bushen yizhi formula is of the effects of strengthening the kidney, replenishing qi, generating marrow and nourishing the brain, its medicine-containing serum can effectively protect these changes resulting from amyloid protein.OBJECTIVE: To investigate whether the medicine-containing serum of bushen yizhi formula can improve the pathological injury of neurons induced by amyloid protein metabolites in Alzheimer disease, thus to estimate the therapeutic effect of bushen yizhi formula on Alzheimer disease.DESIGN:A randomized and controlled trial. SETTING:Institute of Neuroscience, Second Affiliated Hospital, Guangxi College of Traditional Chinese Medicine, Nanning 530011, Guangxi Zhuang Nationality Autonomous Region, China; Encephalopathic Institute of Guangzhou University of Traditional Chinese Medicine.MATERIALS:The experiment was conducted from September 2003 to March 2004 at the Research and Development Center of New Drugs of Guangxi College of TCM. Totally 60 healthy Wistar rats of clean grade,three months, were at random divided as blank control and bushen yizhi groups, with 30 in each group. The bushen yizhi formula consisted of Fructus Lycii, Fructus Cnidii, Radix Gingeng, Radix Polygoni Multiflori,Cortex Moutan Radicis, Borneolum, etc. The medicine was prepared before use as 0.176 g/Ml liquid(including 1.13 g/Ml rude drugs).METHODS:① Each of the rats in bushen yizhi group was by garage given 1.0-1.5 Ml prepared liquid per day for consecutive 30 days. Within 4hours after the last administration the serum was isolated at 5 000 r/min for 5 minutes, filtered aseptically, the compliment was inactivated at 56 ℃,then the medicine-containing serum was obtained. The rats in blank control group were given saline of the same volume, and the serum was prepared with the same method. ② For NG108-15 cells, the concentration of amyloid protein 25-35 segments in the culture liquid was 5 μ mol/L, or 1-42 segments, 200 nmol/L, was suitable. ③ NG108-15 cells was first in cubated for a day in CO2 incubator with Dulbecco-improved Eagle medium of 0.1 molarity at 37 ℃, then 5 μmol/L amyloid protein 25-35 segment or 200 nmol/L segment 1-42 was added to continuously incubate for a day, after that the cell models of Alzheimer disease was ready. Then 50 g/L medicine-containing serum or Dulbecco-improved Eagle medium of blank control group serum was taken to replace the original culture liquid, and the amyloid protein segments of the above-mentioned concentration was still added for maintaining the cell models of Alzheimer disease, after 5 days'differentiation incubation, the indexes were detected with those in non-amyloid protein as control. ④ Western blotting, radioimmunoassay and electrophysiological examination were used to investigate the ChAT activity,synapsin protein level and rate of functional synapse formation of NG108-15cells in Alzheimer disease after treatment with the medicine-containing serum of bushen yizhi formula.MAIN OUTCOME MEASURES :The effects of the medicine-containing serum of bushen yizhi formula on ChAT activity, synapsin protein level,rate of functional synapse formation of NG108-15 cells and frequency of miniature plate potential in NG108-15 cells.RESULTS:Totally 60 rats involved all entered the final result analysis.① The effect of the medicine-containing serum of bushen yizhi formula on ChAT activity: In the conditions when there was no amyloid protein or the final concentration of amyloid protein 1- 42 was 200 nmol/L, the ChAT activity in bushen yizhi group was obviously higher than that in blank control group [(1651.2±134.5), (1336.1±268.2), ( 586.1±223.4),(1290.7±381.5)μmol/(g·h); P ＜ 0.05] . ② The effect of the medicinecontaining serum of bushen yizhi formula on synapsin protein level: The absorbance values of synapsin Ⅰa and Ⅰb, in the conditions when there was no amyloid protein, amyloid protein 25-35 and 1-42, were respectively 5.02, 1.36 and 2.46 in bushen yizhi group; and 3.18, 0.57 and 0.71 in blank control group. The values in bushen yizhi group were respectively 1.6,2.4 and 3.5times those in blank control group. ③ The effect of the medicine-containing serum of bushen yizhi formula on functional synapse formation of NG108-15 cells: In the conditions when there was no amyloid protein or amyloid protein 1-42, the levels of functional synapse formation in bushen yizhi group wereall higher than those in blank control group [(90.6±6.0)%, (63.2±17.0)%, (58.0±13.1)%, (34.2±13.0)% ;P＜0.05].④ The effect of the medicine-containing serum of bushen yizhi formula on frequency of miniature plate potential in NG108-15 cells: In the conditions when there was no amyloid protein or amyloid protein 1-42, the frequencies of miniature plate potential in bushen yizhi group were all higher than those in blank control group [(9.28±4.1), (5.48 ±5.14), (5.55±5.85),(3.05±4.46)/min; P ＜ 0.01, P＜ 0.05].CONCLUSION:In the conditions when there existed no amyloid protein or amyloid protein, the medicine-containing serum of bushen yizhi formula can raise ChAT activity, not only correct the decrease of cellular synapsin caused by amyloid protein, but also raise the expression of synapsin protein, the rate of functional synapse formation and neurotransmitter release under the condition of no amyloid protein. It was shown that the prescription can antagonize the pathological development of Alzheimer disease, and play the therapeutic effect through enhancing the release power of neurotransmitter.

Aim The current study was conducted to investigate the effect of GSTP1 codon 105 polymorphism, alone and in combination with GSTM1-deletion polymorphism, on erythrocyte GST activity in 196 Han Chinese. Methods GST activity was measured in healthy Chinese by a spectrophotometric method (n=196;101 males and 95 females; age range 21～81 years; median 43.5 years). GSTM1 polymorphisms were analyzed by a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. Results The frequency of GSTM1 null genotype was 56.1% and the frequency of I/I, I/V, and V/V genotypes was 60.7%, 35.2% and 4.1%, respectively, in Han Chinese. The mean erythrocyte GST enzyme activity for I/V genotype group(3.53?0.63 U?g -1Hb) was significantly lower than that for I/I genotypes (4.25?1.07 U?g -1Hb, P=0.000), while significantly higher than that for V/V genotypes (2.44?0.67 U?g -1Hb, P=0.004). In GSTM1(-) group, the GST activity of carriers of GSTM1(-)/GSTP1- I/I is significantly higher than that of GSTM1(-)/GSTP1- I/V or-V/V, however, in GSTM1(+) group, there is no difference between different subgroups. There was no significant difference in the mean GST activity among different age groups. Erythrocyte GST activities were significantly higher in females than in males, but not significantly. Conclusion The GST activity measured by CDNB-based assay is probably strongly correlated with the GSTP1 105Val genotype, although other GST enzymes would tend to dilute the GSTP1 genotype effect.

Objective To explore the correlation of the TIAM2 functional gene mutations with the bleeding events in patients with coronary heart disease who undergone PCI and postoperative taken anti-platelet drug clopi-dogrel. Methods One hundred and twenty Chinese Han patients who had undergone PCI and postoperative taken anti-platelet drug clopidogrel were orderly enrolled from Guangdong General Hospital. Followed for 6 months after PCI, PCR sequencing was applied to test TIAM2 promoter region genotyping assay. Results After follow-up six months , 113 cases were remained lost of 7 cases , , including 19 cases with bleeding and 94 cases without bleed-ing; Bleeding risk in patients with diabetes mellitus (OR=3.115) or taking statins (OR=11.539), may be high, but there was no significant difference (P > 0.05); TIAM2 promoter region had three variants (c.3168+3116C>T, c.3168+3261A>G,c.3168+3596A>C), including wild-type, heterozygous, and homozygous. The probability of pa-tients with bleeding were 36.84%, 52.63%and 10.53%, and there is a certain chain of state , but the genotype was not significantly correlated with bleeding events of clopidogrel antiplatelet therapy (P>0.05). Conclusion Clopi-dogrel antiplatelet therapy bleeding events were not significantly correlated with TIAM2 functional gene mutation.

OBJECTIVE:To establish the quality standard for Tongmai pill. METHODS:TLC was used for the qualitative iden-tification of Salvia miltiorrhiza,Angelica sinensis and Carthamus tinctorius. HPLC was used for the content determination of feru-lic acid. The column was Diamonsil C18 with mobile phase of acetonitrile-0.1% aqueous phosphoric acid (17∶83,V/V) at a flow rate of 1 ml/min,the detection wavelength was 316 nm,the column temperature was 30 ℃,and the injection volume was 10 μl.. RESULTS:The TLC of S. miltiorrhiza,A. sinensis and C. tinctorius showed clear spots and good separation. The linear range of ferulic acid was 8-80 μg/ml(r=0.999 8);RSDs of precision,stability and reproducibility tests were lower than 2%;recovery was 97.2%-99.6%(RSD=1.2%,n=6). CONCLUSIONS:The standard can be used for the quality control of Tongmai pill.

Odor and taste are characteristic properties of traditional Chinese medicine (TCM). They are closely related to the chemical compositions in TCM. They are also the outer reflection of TCM quality and an important part of the character identification. This article reviewed the current research on odor and taste identification of TCM, which indicated that odor and taste identification had not been paid enough attention to and its research lagged behind modern social development. Based on current analytical techniques and methods, this article proposed a new idea for odor and taste identification of TCM. The idea emphasized the objectification of odor and taste and TCM identification research should be combined with chemical components analysis.

[ ABSTRACT] AIM:To investigate the characteristics of the intestinal microbial flora in the pregnant women with congenital heart disease fetus ( PW group) and normal pregnant women ( NW group) .METHODS: Stool samples were collected from 15 NW and 17 PW cases.The bacterial genomic DNA was extracted.The 16S rDNA was amplified by PCR, and the second generation of Illumina sequencing was conducted.RESULTS: We obtained 2 696 276 ( NW group) and 2 445 530 ( PW group) optimized sequences.The coverage was greater than 97%.We obtained 77 243 operational taxono-mic units ( OTUs) in NW group and 75 600 OTUs in PW group after a 97%similarity merge.In NW group, the Chao 1 in-dex and the Shannon index were greater than those in PW group.The diversity analysis of microbial population indicated that they were mainly composed of Firmicutes, Proteobacteria and Actinobacteria.In family, the Bifidobacteriaceae and Cori-obacteriaceae were significantly different through analysis of variance.CONCLUSION: The Bifidobacteriaceae and Cori-obacteriaceae may play an important role in the occurrence of congenital heart disease.

OBJECTIVE:To explore the genome-wide methylation differences between coronary heart disease (CHD) patients and healthy volunteers,and to investigate the relationsip of DNA methylation with CHD from epigenetics. METHODS:In case-control study,subjects were divided into CHD group(50 cases)and health control group(50 cases). DNA of 2 groups were sequenced with methylated DNA immunoprecipitation sequencing technology. The genome-wide methylation differences were analyzed and compared between 2 groups. RESULTS:The number of methylation peak in CHD group was higher than health group,with statistical signfi-cance(P<0.05). The methylation peak mainly distributed in 5'UTR,Intron functional elements. The number of reads in AQP1,SHB and other gene promoters in CHD group were lower than health group,and its methylation level decreased. The number of reads in GRK5 and serveal gene promoters on chrX in CHD group were higher than helath group,and its methylation level increased,with sta-tistical significance(P<0.01). CONCLUSIONS:The genome-wide methylation level of CHD patients are higher than those of healthy volunteers. The occurence of CHD is possibly associated with the change of methylation level of related gene promoters.

OBJECTIVE：To excavate and evaluate ADR signals of SGLT 2 inhibitors as canagliflozin ，dapagliflozin and empagliflozin，and to provide reference for rational drug use in the clinic. METHODS ：The proportional reporting ratio （PRR）and reporting odds ratio （ROR）were used to find the adverse drug reactions （ADR）signal of SGLT 2 inhibitors as canagliflozin ， dapagliflozin and empagliflozin from the second quarter of 2013 to the third quarter of 2020 in the US FDA Adverse Event Reporting System （FAERS）. The basic information （including gender ，age，reporting year ，reporting country ，severe ADR ）and safety warning signals of corresponding patients in ADR report were analyzed. RESULTS ：Among 6 029 375 ADR reports ，SGLT2 inhibitors of 43 807 ADR reports were concomitant and suspected drugs ；there were 19 301 ADR reports of canagliflozin ，10 960 ADR reports of dapagliflozin ，13 546 ADR reports of empagliflozin. Except for the ADR patients with unknown gender and missing age ，the gender distribution of the included reports was balanced ，mainly in the range of 50-75 years old. The reporting year was mainly in 2018，and the main reporting country was the United States ，with“hospitalization or prolonged hospitalization ” as the main serious ADR. A total of 573 ADR signals were obtained ，involving 26 systems，mainly focusing on metabolic and nutritional diseases ，endocrine disorders ，kidney and urinary system disease ，infection and invasion diseases ，etc. The results showed that there were 14 main ADR signals in the top 10 ADR of canagliflozin ，dapagliflozin and empagliflozin. The strongest ADR signals of dapagliflozin and empagliflozin were ketoacidosis （PRR＝119.64/140.11，95％CI lower limit of ROR ＝148.28/ 178.78）and fungal infection （PRR＝47.76/34.77，95％ CI lower limit of ROR ＝50.69/36.28）；except above signals in addition ， toe amputation （PRR＝489.79，95％CI lower limit of ROR ＝520.15）and osteomyelitis （PRR＝61.42，95％CI lower limit of ROR＝65.38）were strong in the ADR signals of canagliflozin. CONCLUSIONS ：SGLT2 inhibitors have a higher security risk in metabolic and nutritional diseases ，endocrine disorders ，kidney and urinary system ，and infection and intrusion diseases. Dapagliflozin，canagliflozin and empag liflozin are prone to cause ADR such as ketoacidosis and fungal infection ，while canagliflozin is easy to cause ADRs such as toe amputation and osteomyelitis.

Radiotherapy is an essential part of comprehensive treatment, as well as a radical treatment for head and neck cancer (HNC). The COVID-19 has continued so far, imposing a great impact on cancer care. Since conventional fractionated radiotherapy (CFRT, 2 Gy/F) requires as long as more than six weeks of treatment time, a huge challenge for epidemic control is created for both hospitals and patients. Hypofractionated radiotherapy (Hypo-RT) may be more suitable than CFRT for patients during pandemic by increasing the fraction size, thus reducing fraction number and treatment duration. Early studies have explored the application of Hypo-RT in HNC in palliative setting, which partially proved its safety and effectiveness. Recently, the efforts have been made in definitive treatment using hypofractionated regimen, as well as its combination with systemic treatment and immunotherapy. Indeed, regarding the pandemic of COVID-19, Hypo-RT has been recommended by several expert consensus in the HNC. In this review, relevant research progress was summarized and clinical implication of Hypo-RT in COVID-19 pandemic era was discussed.

With the aging of population, the elderly (≥65 years old) cancer patients have become one of the main populations for cancer care. For inoperable locally advanced head and neck squamous carcinomas, cisplatin-based concurrent chemoradiotherapy is the first-line choice. Several large clinical studies have shown that patients under 70 years of age can still benefit from concurrent chemoradiotherapy, while it should be cautious to apply chemotherapy to patients aged 70-80 years. For elderly patients who are intolerant to cisplatin, carboplatin or other regimens with less gastrointestinal and renal toxicity should be considered. Although anti-epidermal growth factor receptor (EGFR) monoclonal antibodies combined with radiotherapy has been proved to be more effective than radiotherapy alone in total patient population, age-subgroup analysis showed limited benefit in elderly patients. The safety of immune checkpoint inhibitors in elderly patients has been validated and those with high programmed death ligand-1 (PD-L1) expression may benefit from concurrent or neoadjuvant immunotherapy, however, high-level evidence is still lacking. For patients older than 80 years, radiotherapy alone may be superior to concurrent chemoradiotherapy, and hypofractionated radiotherapy for palliative purposes can be safely used in this population.