Introduction to Health Research Priority Setting Methods and Application Recommendations of Methods in Field of Traditional Chinese Medicine / 中国实验方剂学杂志

Health research priority setting， based on the existing disease burden or healthcare needs， screens out specific areas or topics with relatively high research priority by scientific and systematic methods， and optimizes the allocation of health resources by influencing healthcare decision-making， so as to alleviate the imbalance between regional or global health and development. Many developed countries have carried out related research and practical work on different scales， and the World Health Organization （WHO） attaches great importance to the transformation and application of relevant achievements in developing countries. As the largest developing country in the world， China's research in this field started relatively late， and only a small number of scholars have carried out part of the localization methodology research and practice according to the specific national conditions. However， health research priority setting has not yet attracted the attention of large-scale research institutions or government organizations in China. Although the priority setting is rarely mentioned in the research on traditional Chinese medicine （TCM）， the research and decision-making on the diseases responding specifically to TCM can also be regarded as the practical work of exploring the priority of TCM. Policymakers have a sense of priority support in the "priority of TCM research"， but the decisions from the top design are mainly based on the consensus reached by high-level think tanks. There is a lack of extensive research， and moreover， the data of multiple stakeholders are not included. Therefore， it is urgent to introduce appropriate priority setting methods to solve the problem of transparency and scientificity in the decision-making process. Given the perspective of the specific implementation， the present study introduced three international priority setting methods， i.e.， the James Lind Alliance and Priority Setting Partnerships（JLAPSP，）the Child Health and Nutrition Research Initiative（CHNRI）， and the Council on Health Research and Development （COHRED）， and presented relevant recommendations on how to apply them in the research of TCM， which is expected to provide references for the local research.

Clinical Evidence of Chinese Patent Medicines in Treatment of Respiratory Diseases in Children： A Scoping Review / 中国实验方剂学杂志

ObjectiveThis study performed a scoping review to comprehensively analyze and report the information on the instructions of Chinese patent medicines and clinical research evidence for the treatment of respiratory diseases in children. MethodChinese patent medicines against respiratory diseases in children were obtained by searching the three major drug catalogues. The Chinese and English databases were searched for relevant literature，followed by data statistics and visualized analysis. ResultAfter screening and analysis，52 Chinese patent medicines were included，involving nine dosage forms. The main drugs were Scutellariae Radix，Armeniacae Semen Amarum，Forsythiae Fructus，etc. The main functions included clearing heat and releasing exterior syndrome，and relieving cough and dissipating phlegm. The indications mainly included common cold with wind-heat syndrome and cough in children. Adverse drug reactions and contraindications were only specified in 19.23% （10/52） of Chinese patent medicines，and the rest only displayed "unclear". A total of 279 articles were included，including 277 articles from Chinese Core Periodicals and two articles from SCIE. In terms of research type，those articles included 253 randomized controlled trials （RCTs，with six dosage form/dose comparisons involved），11 retrospective analyses based on Hospital Information System （HIS） data，one case series，13 systematic reviews/Meta-analyses （with two network Meta-analyses involved），and one economic evaluation article. Among them，72.76% （203/279） of the articles were published in the Core Journals of Chinese Science and Technology. Only 33 Chinese patent medicines were involved，and Xiaoer Feire Kechuan Oral Liquid was the top 1 under investigation，accounting for 15.71% （44/280）. The indicated diseases were mainly infantile pneumonia，bronchitis，respiratory tract infection，cough，asthma，and other western medicine diseases. Xiaoer Chiqiao Qingre Granules and Xiaoer Dingchuan Oral Liquid were used off-label. The sample size was concentrated in 51-150 cases，accounting for 67.17% （178/265）. The interventions in the experimental group were mainly Chinese patent medicine + western medicine + basic treatment or Chinese patent medicine + western medicine. The main outcomes were the effective rate and the improvement of clinical symptoms. The adverse reactions were mainly gastrointestinal reactions，drug-induced skin symptoms，etc.，and two studies have shown that drug doses were associated with adverse reactions. ConclusionIn research years，the research on Chinese patent medicines in the treatment of respiratory diseases in children has advanced rapidly. However，there are still some problems that need to be resolved in the future，such as incomplete information on drug content in the instruction，concentrated drugs to be studied，limited indications，failure to highlight the characteristics of traditional Chinese medicine （TCM） syndromes，unstandardized research design，and an incomplete reflection of Chinese patent medicine.

Expression and significance of calcitonin and osteopontin in peripheral blood of patients with atrial fibrillation / 中国综合临床

Objective:To investigate the expression levels of serum calcitonin (CT) and osteoponin (OPN) in peripheral blood of patients with atrial fibrillation (AF) and their relationship with AF.Methods:A case control study was conducted, 160 AF patients treated in Shaanxi Provincial People's Hospital from June 2020 to December 2021 were selected as case group, and 160 healthy people in the same period were selected as control group. The expression levels of serum CT and OPN in the two groups were analyzed retrospectively, and the correlation between them and AF was analyzed. The value of CT and OPN levels in predicting the occurrence of AF was analyzed by receiver operating characteristic (ROC). Kappa consistency test was used to analyze the efficacy of the combination of them in predicting the occurrence of AF.Results:The serum calcitonin level ((13.5±3.2) ng/L) in the case group was lower than that in the control group ((17.3±3.1) ng/L), and the osteopontin level ((53.8±8.2) μg/L) was higher than that of the control group ((44.1±6.8) μg/L), the difference between the two groups was statistically significant ( t=10.79, P<0.001; t=11.50, P<0.001). The results of binary logistic regression analysis showed that serum calcitonin was the protective factor of atrial fibrillation ( OR=0.723, 95% CI: 0.661-0.790, P<0.001), and osteopontin was the risk factor ( OR=1.183, 95% CI: 1.131-1.237, P<0.001). ROC analysis showed that the area under curve (AUC) of CT, OPN and their combination in predicting AF were 0.794, 0.824, and 0.892, respectively. The predictive critical value for serum CT was <15.0 ng/L and >48.5 μg/L for OPN. The sensitivity, specificity of the combination in AF prediction were 67.50% and 93.75% respectively, and Kappa value was 0.613. Conclusion:The expression of serum CT and OPN was abnormal in patients with atrial fibrillation. The prediction of AF by combined examination of the two had a high degree of consistency with the actual results, which could provide reference for early diagnosis and treatment of AF. However, the rate of missed diagnosis was relatively high, which needs attention in clinical application.

Serum metabolomics of Tibetan medicine Ershiwuwei Songshi Pills against chronic cholestasis in mice / 中国中药杂志

A chronic cholestasis model was induced in mice by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine(DDC). The effects of Ershiwuwei Songshi Pills(ESP) on endogenous metabolites in mice with chronic cholestasis were investigated by metabolomics analysis based on liquid chromatography-mass spectrometry(LC-MS). The results showed that ESP was effective in improving pathological injury and reducing serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid in the model mice. Meanwhile, 13 common differential metabolites were revealed in metabolomic screening between the model/control group and the model/ESP group, including uric acid, glycolaldehyde, kynurenine, flavin adenine dinucleotide, L-3-phenyllactic acid, I-urobilin, leukotriene D4(LTD4), taurocholic acid, trioxilin A3, D-inositol-1,4-diphosphate, PC [16:0/20:2(11Z,14Z)], PC[14:0/22:2(13Z,16Z)], and PC[20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z)]. After ESP intervention, the levels of all 13 differential metabolites were significantly retraced, and pathway analysis showed that ESP achieved its therapeutic effect mainly by affecting arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. This study elucidated the mechanism of action of ESP against chronic cholestasis based on metabolites.

Efficacy of remimazolam combined with alfentanil for gastroscopy in frail elderly patients / 中华麻醉学杂志

Objective:To evaluate the efficacy of remimazolam combined with alfentanil for gastroscopy in frail elderly patients.Methods:Sixty American Society of Anesthesiologists physical status Ⅱ or Ⅲ elderly patients, aged 65-85 yr, with body mass index of 18-30 kg/m 2, of Clinical Frailty Scale score≥5, scheduled for elective painless gastroscopy, were divided into 2 groups ( n=30 each) using a random number table method: remimazolam combined with alfentanil group (group R) and propofol combined with remifentanil group (group P). A combination of alfentanil 10 μg/kg and remimazolam 0.2 mg/kg was intravenously injected until loss of consciousness in group R. Remifentanil 0.5 μg/kg combined with propofol 1.0-2.0 mg/kg was intravenously injected until loss of consciousness in group P. According to the intraoperative conditions, 1/4 of the initial dose of remimazolam was intravenously injected in group R, and 1/4 of the initial dose of propofol was intravenously injected in group P. The time for gastroscopy, requirement for additional remimazolam or propofol, onset time of anesthesia, emergence time and time of post-anesthesia care unit stay were recorded.Physician′s satisfaction scores, patient′s satisfaction scores and Verbal Pain Scale scores were recorded.The occurrence of injection pain, respiratory depression, bradycardia, hypotension and nausea and vomit was recorded. Results:There was no significant difference in the requirement for additional remimazolam or propofol, onset time of anesthesia, time for gastroscopy, physician′s satisfaction scores, and patient′s satisfaction scores, Verbal Pain Scale scores and incidence of nausea and vomit between two groups ( P>0.05). Compared with P group, the emergence time and time of post-anesthesia care unit stay were significantly shortened, and the incidence of injection pain (0 vs.33%), respiratory depression (0 vs.20%), hypotension (3% vs.23%) and bradycardia (3% vs.23%) was decreased in R group ( P<0.05). Conclusions:Remimazolam combined with alfentanil is safe and effective, with rapid recovery from anesthesia, and provides better efficacy than the combination of propofol and remifentanil when used for gastroscopy in frail elderly patients.

Effect of propofol on proliferation, invasion and migration of human melanoma cells and role of COX-2/PGE2/MMP signaling pathway / 中华麻醉学杂志

Objective:To evaluate the effect of propofol on proliferation, invasion and migration of human melanoma cells and role of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2)/matrix metalloproteinase (MMP) signaling pathway.Methods:SKMEL-5 cells were cultured in vitro and divided into 4 groups ( n=36 each) using the random number table method: control group (group C), propofol group (group P), COX-2 overexpression group (group COX-2), and COX-2 overexpression plus propofol group (group COX-2+ P). Propofol at the final concentration of 60 μmol/L was added in group P. The COX-2 overexpression plasmid pcDNA3.1-COX-2 was transfected into SKMEL-5 cells in group COX-2 and group COX-2+ P, and propofol at the final concentration of 60 μmol/L was added in group COX-2+ P.After incubation for 48 h, the cell proliferation rate was determined by CCK-8 method, the cell invasion and migration ability was determined by Transwell assay, the expression of COX-2 in cells was detected by Western blot, the expression of COX-2 mRNA in cells was detected by quantitative real-time polymerase chain reaction, and the concentrations of serum PGE2, MMP-2 and MMP-9 were determined by enzyme-linked immunosorbent assay. Results:Compared with group C, the cell proliferation rate was significantly decreased, the number of cell invasion and migration was decreased, the expression of COX-2 protein and mRNA was down-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were decreased in group P, and the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2 ( P<0.05). Compared with group P, the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2+ P ( P<0.05). Conclusions:Propofol can inhibit the proliferation, invasion and migration of human melanoma cells, and the mechanism may be related to inhibition of the COX-2/PGE2/MMP signaling pathway.

A study on certolizumab pegol in the treatment of inflammatory joint diseases of women of childbearing age / 中华风湿病学杂志

Objective:To evaluate the efficacy of certolizumab pegol (CZP) in the treatment of Chinese women of childbearing age with inflammatory joint diseases and the effect of intrauterine exposure on infant vaccination and risk of infection.Methods:This study is a retrospective observation study, including female patients of childbearing age who were treated with CZP in the outpatient clinic from November 2019 to October 2020. The patients were followed up for 24 weeks, and the related data was collected. We adopted disease activity score-28 for rheumatoid arthritis with CRP (DAS28-CRP), clinical disease activity index (CDAI) and simplified disease activity index (SDAI) to evaluate disease activity. Bath ankylosing spon-dylitis disease activity index (BASDAI) and ankylosing spondylitis disease activity score (ASDAS-ESR) were used to assess the disease activity of patients with ankylosing spondylitis or spondyloarthritis (AS/SpA). Low disease activity (LDA), the dosage of glucocorticoid (GC) and the qualified rates of ACR20 and ASAS20 were calculated to validate the efficacy of CZP. The data of infants vaccination and infection was recorded to estimate the effect of intrauterine exposure on infants. Correlation analysis were performed using paired t test or Mann Whitney test. All statistical tests were bilateral, with a significance of P<0.05. Results:Twenty women entered the study and fifteen completed, including eight patients with RA, six patients with AS and 1 patient with SpA. The average age was (30±5) years and the median symptom duration was 5.0 (3.0, 6.5) years. When these RA patients were enrolled into the study, DAS28-CRP, CDAI and SDAI were (3.4±1.2), 15.5(9.5, 21.0) and (18±12) respectively; and after the use of CZP, the DAS28-CRP, CDAI and SDAI changed to (2.5±0.9)( t=2.48, P=0.042), 4.5(3.5, 10.8) ( U=12.50, P=0.040) and (9±6) (t=2.76, P=0.028). At the first follow-up, the ACR20 rate was 50%. and at the end of the study, the LDA rate was 75%(6/8), three(37.5%) women reduced the dosage of GC. Among the AS/SpA patients, BASDAI was 19.0(14.5, 26.0) and ASDAS-ESR was (2.4±1.0) at first, while after treatment, BASDAI turned into 9.0(1.0, 10.5) ( U=11.50, P=0.100) and ASDAS-ESR turned into (1.4±0.5) ( t=3.44, P=0.014). The ASAS20 rate at the first follow-up was 71.4%(5/7), and 85.7%(6/7) at the end of the study. Four patients experienced adverse events, resulting in drug withdrawal. Three women were pregnant when they were enrolled into the study, and three others became pregnant during the research. Six infants were vaccinated with live attenuated vaccines and inactivated vaccines according to the plan. No adverse event related to vaccination was reported, but one of the babies had perianal abscess and the other one had cold symptoms, while both improved after treatment. Conclusion:CZP can effectively control disease activity of women with inflammatory joint diseases during pregnancy, and intrauterine exposure is safe to infants during the study period.

c-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

ALDH3B1 expression is correlated with histopathology and long-term prognosis of gastric cancer / 南方医科大学学报

OBJECTIVE@#To investigate the expression of aldehyde dehydrogenase 3B1 (ALDH3B1) in gastric cancer and explore its correlation with the pathological parameters and long-term prognosis of the patients.@*METHODS@#We analyzed the clinical data of 101 patients who underwent radical gastrectomy for gastric cancer in our hospital between January, 2013 and November, 2016, and examined the expression of ALDH3B1 in paraffin-embedded samples of gastric cancer tissues and adjacent tissues from these cases by immunohistochemical staining. We evaluated the correlation between ALDH3B1 expressions and histopathological parameters and assessed the predictive value of ALDH3B1 expression for long-term survival of the patients. We also examined the effect of lentivirus-mediated interference and overexpression of ALDH3B1 on the malignant behaviors of MGC-803 gastric cancer cells.@*RESULTS@#The expressions of ALDH3B1 and Ki67 were significantly higher in gastric cancer tissues than in adjacent tissues (P < 0.05). In gastric cancer patients, ALDH3B1 expression was positively correlated with peripheral blood CEA and CA19-9 levels (P < 0.01). The proportion of patients with CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T stage of 3- 4, and N stage of 2-3 was significantly greater in high ALDH3B1 expression group than in low expression group. Kaplan-Meier survival analysis showed that the 5-year survival rate was significantly lower in gastric cancer patients with high ALDH3B1 expressions (P < 0.01). Univariate and Cox multiple regression analyses identified a high expression of ALDH3B1 (P < 0.05, HR= 0.231, 95% CI: 0.064-0.826), CEA≥5 μg/L (P < 0.01, HR=4.478, 95% CI: 1.530-13.110), CA19-9≥37 kU/L (P < 0.01, HR=3.877, 95% CI: 1.625-9.247), T stage of 3-4 (P < 0.01, HR=4.953, 95% CI: 1.768-13.880), and N stage of 2-3 (P < 0.05, HR=2.152, 95% CI: 1.152-4.022) as independent risk factors affecting 5-year survival after radical gastrectomy. The relative ALDH3B1 expression level, at the cut-off point of 4.66, showed a sensitivity of 76.47% and a specificity of 76% for predicting 5-year postoperative death (P < 0.01). In the cell experiment, overexpression of ALDH3B1 obviously promoted the proliferation, migration and invasion of MGC-803 cells.@*CONCLUSION@#As an independent risk factor affecting 5-year survival after radical gastrectomy, ALDH3B1 is highly expressed in gastric cancer and correlated with pathological parameters of the tumor, and a high ALDH3B1 expression may promote proliferation, invasion and metastasis of gastric cancer cells.

Effect of fudosteine on lung cancer cells in an inflammatory microenvironment based on metabolomics / 药学学报

GC-MS metabolomics was used to investigate the effects of fudosteine on lung cancer A549 cells in an inflammatory microenvironment. Eleven metabolites (malic acid, isoleucine, lactose, galactinol, creatinine, gluconic acid, oleic acid, phosphate, S-carboxymethyl-L-cysteine, uridine and tagatose) were identified in the metabolomics results and could be used as biomarkers of fudosteine treatment. Pathway enrichment analysis showed that the metabolic pathways of amino acids including isoleucine, valine, leucine, glycine, serine and threonine were significantly altered, as were the metabolic pathways of carbohydrates such as galactose and pentose phosphate. Fudosteine significantly reduced the level of inflammatory factors in A549 cells and corrected the inflammatory microenvironment by interfering with the effects of amino acid metabolites and amino acid metabolism pathways. This study reveals that fudosteine may be able to inhibit the continuous inflammatory response and prevent the further progression of lung cancer by suppressing the inflammatory microenvironment.

Clinical Evidence on Treatment of Otorhinolaryngologic Diseases with Oral Chinese Patent Medicine： A Scoping Review / 中国实验方剂学杂志

This paper aims to systematically retrieve and summarize the clinical evidence on oral Chinese patent medicine in otorhinolaryngology by scoping review and analyze the distribution of the evidence， which is expected to serve as a reference for clinical practice and healthcare decision-making. Seven databases were searched （from inception to March 2022） for the clinical evidence of oral Chinese patent medicine in the prevention and treatment of otorhinolaryngologic diseases， and the distribution of the evidence was discussed. A total of 248 papers from core journals/SCI were included： 238 clinical studies （185 randomized controlled trials， 46 semi-/non-randomized controlled trials， 7 case series studies）， 5 systematic reviews， 4 guidelines/expert consensuses， and 1 pharmacoeconomic study. The papers covered 26 oral Chinese patent medicines and 40 otorhinolaryngological diseases （5 ear diseases， 22 nose diseases， and 13 throat diseases）. The majority of the clinical studies included 100-300 cases. The combination of Chinese patent medicine and western medicine is the common intervention in the experimental group. The outcomes were mainly “cure rate” and improvement of clinical symptoms. Common adverse events were nausea， vomiting， rash， headache， gastrointestinal discomfort， fatigue， etc. In summary， there is a lack of high-quality clinical evidence on oral Chinese patent medicine in otorhinolaryngology. In addition， the available studies have such problems as seldom use of recognized outcomes， low quality of clinical studies， and lack of pharmacoeconomic study. In future， efforts should be made to carry out more rigorous primary and secondary research and enhance the pharmacoeconomic evaluation， in a bid to explore the advantages of Chinese patent medicine in the treatment of otorhinolaryngologic diseases and promote the more rational allocation and application of health resources.

Myricetin inhibits interferon-γ-induced programmed death ligand-1 and indoleamine 2, 3-dioxygenase 1 expression in lung cancer cells / 中国药理学与毒理学杂志

OBJECTIVE Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints which can be induced by interferon-γ(IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells. METHODS Expressions of PD-L1 and major histocompatibility complex-I (MHC-I) were evaluated by flow cytometry and Western blotting, and the expression of IDO1 was measured by Western blotting. qRT-PCR was used to detect their mRNA levels. The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1. Molecular docking analysis, Western blotting and immunofluorescence were used for mechanism study. RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells, while didn't show obvious effect on the expression of MHC-I. In addition, MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression, supporting the potential of MY in anti-tumor immunotherapy.

Quality of life status and influencing factors of patients with tuberculosis and glucose metabolism disorders / 公共卫生与预防医学

Objective To investigate the current status and influencing factors of quality of life in patients with pulmonary tuberculosis complicating glucose metabolism disorders. Methods A total of 117 patients with pulmonary tuberculosis complicating glucose metabolism disorders (combined group) and 121 patients with pulmonary tuberculosis (single group) in our hospital from March 2017 to April 2020 were enrolled. The quality of life of patients was investigated using health survey questionnaire, then the general data of patients were collected and the risk factors of glucose metabolism disorder were analyzed. Results The score of quality of life of patients with pulmonary tuberculosis complicating glucose metabolism disorder was significantly lower than that of patients with pulmonary tuberculosis (P<0.05) . Among patients with pulmonary tuberculosis complicating glucose metabolism disorder, the scores of quality of life among patients of male, age 18-44 years old, monthly income ≥ 4500, good glycemic control, good diet control, and regular daily exercise were higher than those of female patients, age 45-59 years old, age ≥ 60 years old, low monthly income, poor glycemic control, poor diet control and seldom exercise ( P<0.05 ) ; Gender, monthly income, age and blood glucose control were risk factors for quality of life in patients with pulmonary tuberculosis complicating glucose metabolism disorder (P<0.05) . Conclusion The quality of life of patients with pulmonary tuberculosis complicating glucose metabolism disorder is at low level, especially among people of the female, age over 60 years old, a monthly income less than 4500 yuan and poor blood glucose control, so the related health public education is of vital importance in the prevention of worsened quality of life.

Production of curcumin by engineered Escherichia coli / 生物工程学报

Curcumin is exclusively isolated from Zingiberaceae plants with a broad spectrum of bioactivities. In the present study, we used the diketide-CoA synthase (DCS) and curcumin synthase (CURS) genes to construct a non-natural fusion gene encoding diketide-CoA synthase::curcumin synthase (DCS::CURS). This fusion protein, together with the acetyl coenzyme A carboxylase (ACC) and the 4-coumarate coenzyme A ligase (4CL), were introduced into Escherichia coli for the production of curcumin from ferulic acid. The process is divided into two stages, the growth stage using LB medium and the fermentation stage using the modified M9 medium. The yield of curcumin reached 386.8 mg/L by optimizing the induction of protein expression in the growth stage, and optimizing the inoculum volume, medium composition and fermentation time in the fermentation stage, as well as the addition of macroporous resin AB-8 into the second medium to attenuate the toxicity of the end product. The exploitation of the non-natural fusion protein DCS::CURS for the production of curcumin provides a new alternative to further promoting the production of curcumin and the related analogues.

Early therapeutic interventions of traditional Chinese medicine in COVID-19 patients: A retrospective cohort study / 中西医结合学报

OBJECTIVE@#To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action.@*METHODS@#A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8-14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups.@*RESULTS@#The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044).@*CONCLUSION@#In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19.

Effects of Tanreqing Capsule on the negative conversion time of nucleic acid in patients with COVID-19: A retrospective cohort study / 中西医结合学报

OBJECTIVE@#Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19.@*METHODS@#A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored.@*RESULTS@#COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3@*CONCLUSION@#Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3

Research Status of New Targets MRD Detection in Acute Myeloid Leukemia Recurrence--Review / 中国实验血液学杂志

Although most acute myeloid leukemia (AML) patients can achieve complete remission (CR) induced by standardized chemotherapy, but the relapse rate after remission remains high. The key reason is its high heterogeneity in cytogenetics and molecular biology. There are evidences show that minimal residual disease (MRD) is closely associated with disease recurrence, so that, finding specific genetic and molecular biological changes as new targets for MRD detection has become a research hotspot in recent years. In this review the intrinsic relationship between relapse of AML and MRD detection of specific molecular events, the application of these new targets in MRD detection and their targeted therapies according to the latest guidelines, so as to achieve the optimal treatment in CR phase.

MCDB: A comprehensive curated mitotic catastrophe database for retrieval, protein sequence alignment, and target prediction

Mitotic catastrophe (MC) is a form of programmed cell death induced by mitotic process disorders, which is very important in tumor prevention, development, and drug resistance. Because rapidly increased data for MC is vigorously promoting the tumor-related biomedical and clinical study, it is urgent for us to develop a professional and comprehensive database to curate MC-related data. Mitotic Catastrophe Database (MCDB) consists of 1214 genes/proteins and 5014 compounds collected and organized from more than 8000 research articles. Also, MCDB defines the confidence level, classification criteria, and uniform naming rules for MC-related data, which greatly improves data reliability and retrieval convenience. Moreover, MCDB develops protein sequence alignment and target prediction functions. The former can be used to predict new potential MC-related genes and proteins, and the latter can facilitate the identification of potential target proteins of unknown MC-related compounds. In short, MCDB is such a proprietary, standard, and comprehensive database for MC-relate data that will facilitate the exploration of MC from chemists to biologists in the fields of medicinal chemistry, molecular biology, bioinformatics, oncology and so on. The MCDB is distributed on http://www.combio-lezhang.online/MCDB/index_html/.

Effect and Mechanism of Epimedium Polysaccharide on Bone Marrow Hematopoietic Function and Th17/Treg Balance in Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To observe the effects of Epimedium polysaccharides (EPS) on bone marrow hematopoietic function and Th17/Treg balance in aplastic anemia (AA) mice, and preliminarily explore its therapeutic mechanism.@*METHODS@#Forty BALB/C mice were randomly divided into control (control), model (model), stanozolol (stanozolol) and epimedium polysaccharide (EPS) group, with 10 mice in each group. Except for the control group, Acetophenazine, Gy irradiation and cyclophosphamide triple application were used to establish AA models for the other groups. After the model was established, the stanozolol group was intragastrically administered with 4 mg/kg stanozolol suspension, the EPS group was intragastrically administered with 100 mg/kg epimedium polysaccharide, while the control group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage once a day, for 14 consecutive days. The automatic animal blood analyzer was used to detect the changes in peripheral blood hemoglobin (Hb), red blood cells (RBC), white blood cells (WBC) and platelets (PLT), flow cytometry was used to detect the proportion of Treg and Th17 cells, the levels of interleukin 2 (IL-2), interleukin 11 (IL-11) and tumor necrosis factor α (TNF-α) were detected by ELISA, the number of nucleated bone marrow cells was counted, HE staining and immunohistochemical staining were used to detect the number, the proliferation and apoptosis of bone marrow cells, Western blot was used to detect the expression of signal transducer and activator of transcription 3 (STAT3), retinoic acid receptor-related orphan receptor γ (RORγt), transducer and activator of transcription 5 (STAT5) and fork head transcription factor 3 (Foxp3).@*RESULTS@#Compared with the model group, the levels of Hb, RBC, WBC and PLT in the peripheral blood of mice in stanozolol and EPS group significantly increased, the proportion of Th17 cells was significantly reduced, and the proportion of Treg cells significantly increased. The levels of IL-2 and TNF-α in serum were significantly reduced (P<0.05), the level of IL-11 significantly increased (P<0.05), the number of bone marrow nucleated cells significantly increased (P<0.05), the positive rate of Ki-67 significantly increased (P<0.05) and the positive rate of Caspase-3 was significantly reduced (P<0.05). At the same time, the protein expression of STAT3 and RORγt significantly decreased, and the protein expression of STAT5 and Foxp3 increased, the difference showed statistically significant (P<0.05).@*CONCLUSION@#EPS can promote the recovery of bone marrow hematopoietic function in AA mice and improve Th17/Treg imbalance, the mechanism may be related to the inhibition of STAT3/RORγt expression and promotion of STAT5/Foxp3 expression.

Study on Cep63 expression and apoptosis of thyroid papillary carcinoma cell lines TPC-1 / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the effect of centrosomal protein Cep63 on the apoptosis of papillary thyroid carcinoma (PTC) cell lines TPC-1 and underlying mechanism. Methods: With collected PTC tissues and adjacent tissues, Cep63 expression was detected by RT-qPCR and its relationship with clinicopathological factors was analyzed. The experiment included negative control group (NC), low expression group (Cep63(-)) and overexpression group (Cep63(+)), and wild-type TPC-1 cells were transfected with Cep63 lentivirus. The efficiency of Cep63 was detected by western blot (WB) and qRT-PCR. Cell proliferation ability was detected by plate cloning experiment and MTT assay. Cell apoptotic rate was detected by flow cytometry, and expression levels of apoptosis-related proteins were detected by immunohistochemistry and WB. The t-test was used to compare the differences in the means between the two groups, the one-way analysis of variance was used to compare multiple groups, and the chi-square test was used to analyze the association between gene expression levels and pathological factors. Results: Compared with NC group, cell proliferation ability was significantly decreased in Cep63(-) group (3.18±0.07 vs. 2.14±0.09, t=8.54, P<0.01) and significantly increased in Cep63(+) group (3.18±0.07 vs. 3.58±0.10, t=3.21, P<0.05). Apoptotic rates in NC, Cep63 (-) and Cep63 (+) groups were respectively 3.03%±0.24%, 8.66%±0.44% and 1.17%±0.44%, and the flow cytometry showed that the low expression of Cep63 significantly increased the apoptosis TPC-1 cells (F=157.7, P<0.001). Bcl-2 protein expression levels of NC, Cep63 (-) and Cep63 (+) groups were respectively 1.07±0.03, 0.49±0.01 and 1.99±0.09, and BAX protein expression levels of three groups were respectively 0.64±0.02, 1.06±0.01 and 0.21±0.03. WB showed that the expression level of Bcl-2 decreased (F=183.2, P<0.001), while the expression level of BAX was significantly up-regulated (F=283.7, P<0.001). Conclusion: Cep63 may regulate the apoptotic process of TPC-1 cells through Bcl-2/BAX pathway and Cep63 may be a potential oncogene of PTC.