Broad-spectrum ginsentides are principal bioactives in unraveling the cure-all effects of ginseng

Stress and illness connection is complex and involves multiple physiological systems. Panax ginsengs, reputed for their broad-spectrum "cure-all" effect, are widely prescribed to treat stress and related illnesses. However, the identity of ginseng's "cure-all" medicinal compounds that relieve stress remains unresolved. Here, we identify ginsentides as the principal bioactives that coordinate multiple systems to restore homeostasis in response to stress. Ginsentides are disulfide-rich, cell-penetrating and proteolytic-stable microproteins. Using affinity-enrichment mass spectrometry target identification together with in vitro, ex vivo and in vivo validations, we show that highly purified or synthetic ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via intracellular PI3K/Akt signaling pathway, alleviate α1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of aorta, decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40 and inhibit P2Y12 receptors to reduce platelet aggregation. Orally administered ginsentides were effective in animal models to reduce ADP-induced platelet aggregation, to prevent collagen and adrenaline-induced pulmonary thrombosis as well as anti-stress behavior of tail suspension and forced swimming tests in mice. Together, these results strongly suggest that ginsentides are the principal panacea compounds of ginsengs because of their ability to target multiple extra- and intra-cellular proteins to reverse stress-induced damages.

Self-reported quality of life in patients with coronary heart disease and analysis of the associated factors / 中华内科杂志

Objective: To investigate the quality of life and associated factors in patients with coronary heart disease (CHD) in China. Methods: A cross-sectional study of 25 provinces and cities in China was performed from June to September 2020. A questionnaire was used to collect the socio-demographic and clinical information of patients with CHD, while the European Five-dimensional Quality of Life Scale (EQ-5D) was used to assess the quality of life. Multiple linear regression model was performed to analyze the associated factors. Results: The median age of the 1 075 responders was 60 (52, 67) years, and 797 (74.1%) were men. The EQ-5D and EQ-VAS indices were 0.7 (0.5, 0.8) and 60.0 (40.0, 80.0). Among the five dimensions in the quality of life scale, the frequency of anxiety/depression was the highest (59.8%), while problems in self-care was the lowest (35.8%). In the multiple linear regression model, female, increasing age, obesity, comorbidity(ies), anxiety/depression, social media channels, and receiving the CABG therapy were associated with the lower EQ-5D index (all P<0.05). In addition, increasing age, obesity, comorbidity (ies), depression, anxiety and depression, social media channels, and receiving the CABG therapy were associated with lower EQ-VAS index (all P<0.05). Conclusion: Over half of the patients with CHD in China have a low quality of life, which is related to gender, age, obesity, treatment pathway, the presence or absence of comorbidity (ies), and psychological state. In addition to managing the adverse effects of traditional socio-demographic factors on the quality of life, clinical practices should pay attention to the psychological state of patients. Moreover, establishing a WeChat group for doctor-patient communication could improve the quality of life of CHD patients.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Ethyl Lithospermate Reduces Lipopolysaccharide-Induced Inflammation through Inhibiting NF-κB and STAT3 Pathways in RAW 264.7 Cells and Zebrafish / 中国结合医学杂志

OBJECTIVE@#To explore the anti-inflammatory effects of ethyl lithospermate in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine-derived macrophages and zebrafish, and its underlying mechanisms.@*METHODS@#3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays were performed to investigate the toxicity of ethyl lithospermate at different concentrations (12.5-100 µ mol/L) in RAW 264.7 cells. The cells were stimulated with LPS (100 ng/mL) for 12 h to establish an inflammation model in vitro, the production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α (TNF-α) were assessed by enzyme linked immunosorbent assay (ELISA). Western blot was used to ascertain the protein expressions of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) p65, phospho-STAT3 (p-STAT3, Tyr705), inhibitor of NF-κB (IκB) α, and phospho-I κB α (p-IκB α, Ser32), and confocal imaging was used to identify the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705). Additionally, the yolk sacs of zebrafish (3 days post fertilization) were injected with 2 nL LPS (0.5 mg/mL) to induce an inflammation model in vivo. Survival analysis, hematoxylin-eosin (HE) staining, observation of neutrophil migration, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to further study the anti-inflammatory effects of ethyl lithospermate and its probable mechanisms in vivo.@*RESULTS@#The non-toxic concentrations of ethyl lithospermate have been found to range from 12.5 to 100 µ mol/L. Ethyl lithospermate inhibited the release of IL-6 and TNF-α(P<0.05 or P<0.01), decreased IκBα degradation and phosphorylation (P<0.05) as well as the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705) in LPS-induced RAW 264.7 cells (P<0.01). Ethyl lithospermate also decreased inflammatory cells infiltration and neutrophil migration while increasing the survival rate of LPS-stimulated zebrafish (P<0.05 or P<0.01). In addition, ethyl lithospermate also inhibited the mRNA expression levels of of IL-6, TNF-α, IκBα, STAT3, and NF-κB in LPS-stimulated zebrafish (P<0.01).@*CONCLUSION@#Ethyl lithospermate exerts anti-Inflammatory effected by inhibiting the NF-κB and STAT3 signal pathways in RAW 264.7 macrophages and zebrafish.

A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies / 中华血液学杂志

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

Factor analysis of secondary intraocular hypertension after intravitreal dexamethasone implantation in patients with diabetic macular edema / 中华眼底病杂志

Objective:To observe and analyze the risk factors of secondary intraocular hypertension in diabetic macular edema (DME) patients after treatment with dexamethasone vitreous cavity implant (DEX).Methods:A retrospective observational study. A total of 352 patients with type 2 diabetes mellitus (T2DM) secondary macular edema diagnosed by ophthalmic examination and treated with DEX in Department of Ophthalmology of Harbin 242 Hospital from January 2016 to March 2022 were included in the study. Among them, 221 were males and 131 were females, with the mean age of (55.56±8.09) years. There were 194 patients with disseminated macular edema, 158 patients with cystoid macular edema. All patients underwent vitreous cavity implantation of DEX. Intraocular pressure (IOP) was measured once a month for 3 months after treatment, with IOP over than 25 mm Hg (1 mm Hg=0.133 kPa) or higher than 10 mm Hg from baseline as secondary intraocular hypertension. The relevant clinical data were collected, and the risk factors of secondary intraocular hypertension in DME patients after DEX treatment were analyzed by binary logistic regression.Results:Among 352 patients, 116 patients (32.95%, 116/352) were in the intraocular hypertension. Among them, 29 patients (25.00%, 29/116), 69 patients (59.48%, 69/116) and 18 patients (15.52%, 18/116) occurred intraocular hypertension at 1, 2 and 3 months after treatment, respectively. Compared with the normal IOP group, the IOP in the intraocular hypertension group increased significantly at 1, 2 and 3 months after treatment, with statistical significance ( t=10.771, 21.116, 13.761; P<0.001). Compared with normal IOP group, the patients in the intraocular hypertension group had younger age ( t=6.967), longer duration of diabetes ( t=5.950), longer axial length (AL) ( t=14.989), higher proportion of DME grade 3 ( Z=6.284), higher proportion of DEX implantation in pars plana ( χ2=23.275), and higher HbA1c level ( t=10.764), the differences were statistically significant ( P<0.05). Logistic regression analysis showed that longer AL [odds ratio ( OR)=1.428, 95% confidence interval ( CI) 1.054-1.934], DEX implantation in pars plana ( OR=1.358, 95% CI 1.063-1.735), and higher HbA1c ( OR=1.702, 95% CI 1.225-2.366) were the risk factors for secondary intraocular hypertension in DME patients after DEX treatment ( P<0.05), older age was a protective factor ( OR=0.548, 95% CI 0.380-0.789, P<0.05). Conclusions:Long AL, DEX implantation in pars plana and high HbA1c are the risk factors for secondary intraocular hypertension after DEX treatment in DME patients, older age is a protective factor.

Establishment and Validation of Immune Risk Score for Predicting Survival of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To establish an immune gene prognostic model of acute myeloid leukemia (AML) and explore its correlation with immune cells in bone marrow microenvironment.@*METHODS@#Gene expression profile and clinical data of TCGA-AML were downloaded from TCGA database. Immune genes were screened by LASSO analysis to construct prognosis prediction model, and prediction accuracy of the model was quantified by receiver operating characteristic curve and area under the curve. Survival analysis was performed by Log-rank test. Enriched pathways in the different immune risk subtypes were evaluated from train cohort. The relationship between immune prediction model and bone marrow immune microenvironment was verified by flow cytometry in the real world.@*RESULTS@#Patients with low-risk score of immune gene model had better prognosis than those with high-risk score. Multivariate analysis showed that the immune gene risk model was an independent prognostic factor. The risk ratio for AML patients in the training concentration was HR=24.594 (95%CI: 6.180-97.878), and the AUC for 1-year, 3-year, and 5-year overall survival rate was 0.811, 0.815, and 0.837, respectively. In addition, enrichment analysis of differential gene sets indicated activation of immune-related pathways such as cytokines and chemokines as well as autoimmune disease-related pathways. At the same time, real world data showed that patients with high immune risk had lower numbers of CD8+T cells and B lymphocytes compared with low immune risk patients.@*CONCLUSION@#We constructed a stable prognostic model for AML, which can not only predict the prognosis of AML, but also reveal the dysregulation of immune microenvironment.

Prognostic significance of IKZF1 gene deletions in patients with B-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.

Clinical Characteristics and Prognosis of Elderly Patients with Medium and High risk Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and prognosis of patients with medium and high risk myelodysplastic syndrome (MDS).@*METHODS@#97 MDS patients above the age of 60 treated in Nanfang Hospital, Southern Medical University from February 2011 to August 2020 were enrolled. The clinical characteristics and prognosis of the MDS patients with medium risk, high risk or very high risk based on IPSS-R category were retrospectively analyzed. According to the difference of treatment regimes, the patients were divided into the transplantation group, chemotherapy group and other treatment group, and the efficacy among the patients in the 3 groups were analyzed.@*RESULTS@#MDS with excess blast (MDS-EB) in the elderly patients with medium and high risk MDS were the most common, 47.4% of the patients with abnormal chromosome karyotypes, and 23.7% with complex karyotypes (≥3). 97.3% of the patients showed at least one gene mutation, and TP53 mutations were detected in nearly 20% of the patients with medium and high risk. Multivariate analysis showed that IPSS-R category and treatment regimes were the factors affecting the prognosis of elderly patients with medium and high risk MDS. The median overall survival (OS) time of the patients in the 3 groups showed significant difference (P=0.012), and the median OS of the patients in the transplantation group was significantly longer than that in the chemotherapy group and other group (P=0.003,P=0.014,respectively), while there was no significant difference in median OS between chemotherapy group and other treatment group (P=0.685).@*CONCLUSION@#Elderly MDS patients with medium and high risk can benefit from allogeneic hematopoietic stem cell transplantation, which will prolong their OS.

Evaluation of Multidrug Resistant Loop-mediated Isothermal Amplification Assay for Detecting the Drug Resistance of / 生物医学与环境科学（英文）

Objective@#To evaluate multidrug resistant loop-mediated isothermal amplification (MDR-LAMP) assay for the early diagnosis of multidrug-resistant tuberculosis and to compare the mutation patterns associated with the @*Methods@#MDR-LAMP assay was evaluated using 100 @*Results@#The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MDR-LAMP were 85.5%, 93.6%, 96.7%, and 74.4% for the detection of resistance to isoniazid and rifampicin, respectively, and 80.5%, 92.3%, 98.6%, and 41.4% for the detection of @*Conclusion@#MDR-LAMP is a rapid and accessible assay for the laboratory identification of rifampicin and isoniazid resistance of

Correlation between U2AF1 Gene Mutation Characteristics and Clinical Manifestations and Prognosis in Patients with Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation between U2AF1 gene mutation and clinical manifestations and prognosis in patients with myelodysplastic syndromes (MDS).@*METHODS@#The clinical data of 203 MDS patients who accepted Next Generation Sequencing (NGS) was retrospectively analyzed in Nanfang Hospital, Southern Medical University from December 2012 to October 2019. According to whether the patients had U2AF1 gene mutation, the patients were divided into U2AF1 mutated group and non-mutated group, and the relationship between gene mutation characteristics and clinical manifestations and prognosis was analyzed. Then according to the difference of the mutation site of U2AF1, the patients in U2AF1 mutated group were divided into U2AF1@*RESULTS@#The incidence of U2AF1 mutation in MDS patients was approximately 11.3% (23/203), and the mutation frequency of U2AF1 allele was 32.5%. The male ratio in U2AF1 mutated group was significantly higher than that in U2AF1 non-mutated group (P=0.001). There was no patient who had complex karyotypes or TP53 gene mutation in U2AF1 mutated group. There were no significant differences in ages, blood parameters, bone marrow blasts, WHO 2016 classification, IPSS-R category, chromosomal abnormalities like del(5q), -7/del(7q), del(20q), +8, and gene mutation like ASXL1, DNMT3A, RUNX1, SF3B1, and SRSF2 mutation between U2AF1 mutated group and the non-mutated group. Compared with the non-mutated group, there was no significant difference in the overall survival time (P=0.377), the time of acute myeloid leukemia (AML) transformation (P=0.681), and the response rate to hypome- thylating agents in U2AF1 mutated group (P=0.556). Besides, no differences were observed in sex, diagnosis age, WHO 2016 classification, IPSS-R category, blood parameters, overall survival time, and AML transformation time between U2AF1@*CONCLUSION@#The U2AF1 gene mutation dose not affect the survival time, AML transformation time, and response rate to hypomethylating agents in MDS patients. Besides, there are no statistical differences in the clinical characteristics and prognosis of MDS patients between U2AF1

A new nor-sesquiterpene glycoside from Corydalis edulis / 中国中药杂志

This study is to investigate the chemical constituents from the whole plant Corydalis edulis. The chemical constituents were separated and purified by macroporous resin D101, silica gel, Sephadex LH-20, ODS, and semi-preparative HPLC. Their structures were determined by physicochemical properties and spectroscopic data. Four compounds were isolated from the dichloromethane and water extracts of the whole plant C. edulis, and identified as 6'-β-D-xylosylicariside B2(1),(3S,5R,6S,7E)-5,6-epoxy-3-hydroxy-7-megastigmen-9-one(2), loliolide(3), and 5,5'-dimethoxybiphenyl-2,2'-diol(4), respectively. Compound 1 is a new compound, of which the absolute configuration was established by electronic circular dichroism(ECD) calculations. Compound 4 is obtained from the plants of Papaveraceae family for the first time. Compounds 2 and 3 are firstly isolated from the Corydalis genus.

Two new phenylpropanoid amide glycosides from whole plants of Corydalis racemosa / 中国中药杂志

Two new phenylpropanoid amide glycosides and ten analogues were isolated from the CH_2Cl_2 layer of 95% ethanol extract of the whole plants of Corydalis racemosa by using various chromatographic techniques, including silica gel, Sephadex LH-20, ODS column chromatographies, and semi-preparative HPLC. Their structures were identified on the basis of physicochemical properties, MS, NMR, and IR spectroscopic data as N-cis-sinapoyltyramine-4'-O-β-glucoside(1), N-cis-sinapoyl-3-methoxytyramine-4'-O-β-glucoside(2), N-cis-sinapoyltyramine(3), N-cis-feruloyltyramine(4), N-trans-cinnamoyltyramine(5), N-trans-feruloylphenethylamine(6), N-trans-p-methoxycinnamoyl-3-hydoxyoctopamine(7), N-cis-feruloyl-3-methoxytyramine(8), N-trans-feruloyltyramine(9), N-trans-feruloyl-3-methoxytyramine(10), N-trans-sinapoyltyramine(11), and N-trans-p-coumaroyltyramine(12). Compounds 1 and 2 are new compounds. Compounds 3-7 are obtained from the plants of Papaveraceae for the first time, and compounds 8-12 are firstly isolated from C. racemosa.

Analysis of gene mutation sites in patients with failed anti-HIV-1 treatment in Lincang City from 2011 to 2018 / 中华疾病控制杂志

Objective To understand the major genotype-resistant mutation sites and change trends of HIV/AIDS patients with failure of antiviral therapy (ART) in Lincang City, Yunnan Province. Methods The In-House method was used to amplify the Pol gene region in the plasma samples of HIV/AIDS patients with failure of ART in Lincang City from 2011 to 2018. The target sequence was spliced and submitted to the HIV resistance database to identify and analyze the HIV-1 subtypes and resistant mutation sites. Results The 950 strains of HIV/AIDS patients with antiviral failure were mainly CRF08_BC, accounting for 75.5% (717/950), and the total gene mutation rate was 67.1% (637/950), which was dominated by non-nucleoside reverse transcriptase inhibitors (NNRTIs), accounting for 62.4% (593/950); followed by nucleoside reverse transcriptase inhibitors (NRTIs), accounting for 34.7% (330/950); protease inhibitors (PIs) was 7.5% (71/950). A total of 15 NRTIs of resistance-related mutation sites were detected, mainly M184V (29.3%) which was detected mostly in AZT/D4T+3TC+NVP programs; including 17 kinds of NNRTIs, mainly was K103N/S (25.1%)，the most detected in AZT/TDF+3TC+EFV programs. There were 22 kinds of PIs，mainly secondary sites were L10F/V/I (2.2%) and L33F (2.1%). The top three NRTIs mutation sites in the area were changed from T69D/N/G，M184I/V and D67N/G/S to M184I/V, K70R/Q/E/T and T215Y/F/V/I/N/A/D. NNRTIs mutation sites were changed from V179D/T/E/F, E138A/K/G/R and Y181C/F/G/V to K103N/S, E138A/K/G/R and V179D/T/E/F. The mutation sites of the first three PIs did not change much. Conclusions The second-line regimen based on PIs is a better choice in free antiviral treatments. Mastering the drug resistance of different gene mutations is beneficial to the compatibility of first-line drugs, thus delaying the use of second-line drugs.

Analysis on molecular epidemiological characteristics of 38 HIV-1 positive seroconcordant couples in Yunnan Province / 中华疾病控制杂志

Objective To analyze the molecular epidemiological characteristics of 38 HIV-1 positive seroconcordant couples in Yunnan Province. Methods The samples of HIV-1 antibody screened initially and positive confirmed in the Laboratory of Yunnan Provincial Infectious Diseases Specialist Hospital from 2014 to 2016 and laboratory data were collected. 41 samples from HIV-1 positive seroconcordant couples were selected and sequenced by RT-nested-PCR amplification. After the sequences were aligned and spliced, the qualified pol gene region sequence was used to construct phylogenetic tree and analyze subtypes, and the gene distance differences between each positive couple were calculated. Results A total of 76 pol gene regions from 38 HIV-1 positive seroconcordant couples were obtained. The major gene subtypes included CRF08_BC (45,59.2%), CRF07_BC (18,23.7%) and CRF01_AE (7,9.2%), there were also C (4, 5.3%) and B (2, 2.6%). Phylogenetic tree analysis and gene distance calculation clearly showed that HIV transmission between relationship partners occurred in 9 HIV-1 positive seroconcordant couples. Conclusions As the proportion of sexual transmission of HIV has risen year by year, the transmission between husband and wife should be the focus of our attention. Late diagnosis of HIV infection is the main factor that causes the transmission between husband and wife. For special populations, monitoring and testing should be strengthened as soon as possible, so as to reduce the occurrence of transmission between AIDS couples.

NNN Pincer Ru(II)-Complex-Catalyzed α-Alkylation of Ketones with Alcohols.

A series of novel ruthenium(II) complexes supported by a symmetrical NNN ligand were prepared and fully characterized. These complexes exhibited good performance in transfer hydrogenation to form new C-C bonds using alcohols as the alkylating agents, generating water as the only byproduct. A broad range of substrates, including (hetero)aryl- or alkyl-ketones and alcohols, were well tolerated under the optimized conditions. Notably, α-substituted methylene ketones were also investigated, which afforded α-branched steric hindrance products. A potential application of α-alkylation of methylene acetone to synthesize donepezil was demonstrated, which provided the desired product in 83% yield. Finally, this catalytic system could be applied to a one-pot double alkylation procedure with sequential addition of two different alcohols. The current protocol is featured with several characteristics, including a broad substrate scope, low catalyst (0.50 mol %) loadings, and environmental benignity.

Measurement Uncertainty Assessment for Determination of Allura Red in Puffed Food by HPLC / 华中科技大学学报（医学）（英德文版）

This study aimed to assess the measurement uncertainty of a new method for determination of allura redin food by high performance liquid chromatography (HPLC).The uncertainty of mathematical model of allura red is based on Europe for Analytical Chemistry(EURACHEM) guidelines.The sources and components of uncertainty were calculated,including recovery,working solution,sample mass,final volume,response of standard solution,response of sample solution.The expanded uncertainty was 0.0024 (k=2).Uncertainty of working solution was the most significant factor contributing to the total uncertainty,accounting for 86.2％.The uncertainty of volume accounted for the minimum at 0.025％.The developed method is simple and accurate,which can be used for the determination of allura redin puffed samples.

Measurement Uncertainty Assessment for Determination of Allura Red in Puffed Food by HPLC / 华中科技大学学报（医学）（英德文版）

This study aimed to assess the measurement uncertainty of a new method for determination of allura redin food by high performance liquid chromatography (HPLC).The uncertainty of mathematical model of allura red is based on Europe for Analytical Chemistry(EURACHEM) guidelines.The sources and components of uncertainty were calculated,including recovery,working solution,sample mass,final volume,response of standard solution,response of sample solution.The expanded uncertainty was 0.0024 (k=2).Uncertainty of working solution was the most significant factor contributing to the total uncertainty,accounting for 86.2％.The uncertainty of volume accounted for the minimum at 0.025％.The developed method is simple and accurate,which can be used for the determination of allura redin puffed samples.

Application of alkaloids in reversing multidrug resistance in human cancers / 中国天然药物

Multidrug resistance (MDR) in human cancer is one of greatest challenges in cancer therapy. Natural products, especially the alkaloids, exert reversed effects on MDR with low toxicity, by interacting with various targets. In this review article, we summarize the recent progress made in the research of the main alkaloids, including classification, function, mechanism, research status, and application in reversing MDR.

Application of alkaloids in reversing multidrug resistance in human cancers / 中国天然药物

Multidrug resistance (MDR) in human cancer is one of greatest challenges in cancer therapy. Natural products, especially the alkaloids, exert reversed effects on MDR with low toxicity, by interacting with various targets. In this review article, we summarize the recent progress made in the research of the main alkaloids, including classification, function, mechanism, research status, and application in reversing MDR.