HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014-2020 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China.@*METHODS@#A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database.@*RESULTS@#A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs.@*CONCLUSION@#The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Molecular mechanism of Chuanxiong Rhizoma in treating coronary artery diseases / 中草药·英文版

Objective: Most of the studies on the herb Chuanxiong Rhizoma (CR) have focused on the L-arginine-nitric oxide (NO) pathway, but the nitrate-nitrite-NO (NO

Materiamedica literature study on medicinal properties and utility of four kinds of Alpinia Chinese medicines / 中国中药杂志

In order to explore the correlation between the medicinal properties，efficacy and application in the same genetic relationship，explain the scientific connotation of the medicinal properties and effects of traditional Chinese medicines(TCM)，promote the academic development of the theory of traditional Chinese medicines，and provide reference for the research and development of the traditional Chinese medicines of a same genus. In this paper, a literature study of ancient and modern works of Chinese herbal medicine was conducted to investigate the correlation between the properties, meridians tropism, efficacy and application of Alpinia officinarum， A. katsumadai， Galangae Fructus and Alpinae Oxyphyllae Fructus, four kinds of Alpinia Chinese medicines．The results showed that the similar properties of these four kinds of Alpinia Chinese medicines included that they were acrid, warm,and mainly getting into the spleen and stomach channels; the similar efficacies included that dispelling cold，relieving pain，warming stomach，anti-nausea，anti-diarrheal，reinforcing spleen to promote digestion and other effects; in application aspects, the similarities were that they were all mainly used in treatment of catching cold or spleen deficiency induced by abdominal pain，vomiting，diarrhea,diet indigestion, etc. indicating that phylogenetic relationship was closely related with the herbal properties, efficacy and application. It is an effective way to explore，collate and research traditional Chinese medicine by using plant phylogenetic relationships in exploring the internal relations and laws of TCM theories，material bases, pharmacological effects and clinical applications, also with a strong maneuverability to explain their scientific connotation.

Pathomechanisms of podocyte injury in diabetic nephropathy and interventional effects of Chinese herbal medicine / 中国中药杂志

Podocyte injury is closely related to proteinuria in the progress of diabetic nephropathy(DN). The pathological characters of podocyte injury mainly refer to the change of podocyte form and function, including foot process effacement, reduction of podocyte number and density, podocyte apoptosis, podocyte epithelial-mesenchymal transdifferentiation(EMT)and podocyte hypertrophy. These pathological damages are controlled by multiple signaling pathways in the kidney, such as mammalian target of rapamycin(mTOR)/autophagy pathway, transforming growth factor(TGF)-β1 pathway and Notch pathway. For podocyte injuries induced by high glucose or in murine models of DN, some Chinese herbal medicine(CHM)extracts, such as multiglycoside of Tripterygium wilfordii(GTW), triptolide(TP), astragaloside IV(AS-IV), astragalus polysaccharide(APS)and Panax notoginseng saponins(PNS), have the protective effects in vivo or in vitro. The preliminary studies in China showed that GTW improves podocyte injury in the DN model rats probably through regulating the activity of mTORC1 signaling pathway in the kidney. Therefore, it is the developmental direction for the further study to clarify the interventional effects of CHM based on podocyte injury-related signaling pathway in DN.

Regulative mechanisms of mammalian target of rapamycin signaling pathway in glomerular hypertrophy in diabetic nephropathy and interventional effects of Chinese herbal medicine / 中国中药杂志

Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy (DN), and its regulatory mechanism is closely related to mammalian target of rapamycin (mTOR) signaling pathway activity. mTOR includes mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase(Akt)/adenosine monophosphate activated protein kinase(AMPK), and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins(4EBP) and phosphoprotein 70 S6Kinase(p70S6K). Some Chinese herbal extracts could improve cell proliferation via intervening the expressions of the key molecules in the upstream or downstream of PIK/Akt/mTOR signaling pathway in vivo. As for glomerular mesangial cells(MC) and podocyte, mTOR plays an important role in regulating glomerular inherent cells, including adjusting cell cycle, energy metabolism and matrix protein synthesis. Rapamycin, the inhibitor of mTOR, could suppress glomerular inherent cell hypertrophy, cell proliferation, glomerular basement membrane (GBM) thickening and mesangial matrix deposition in model rats with DN. Some Chinese herbal extracts could alleviate glomerular lesions by intervening mTOR signaling pathway activity in renal tissue of DN animal models or in renal inherent cells in vivo and in vitro.

Clinical implication of urinary protein markers in diabetic nephropathy and interventional effects of Chinese herbal medicine / 中国中药杂志

In clinic, some urinary protein makers can dynamically and noninvasively reflect the degree of renal tubular injury in patients with diabetic nephropathy (DN). These urinary biomarkers of tubular damage are broadly divided into two categories. One is newfound, including kidney injury molecule-1 (Kim-1), neutrophil getatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP) and cystatin C (CysC); the other one is classical, including beta2 microglobulin (beta2-MG), retinal binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG). It is reported that, the increases in urinary protein markers are not only closely related to the damage of tubular epithelial cells in DN patients, but also can be ameliorated by the treatment with Chinese herbal compound preparations or Chinese herbal medicine. Recently, although urinary proteomics are used in the protein separation and identification, the traditional associated detection of urinary protein markers is more practical in clinic. At present, it is possible that the associated detection of urinary biomarkers of glomerular and tubular damages may be a feasible measure to reveal the clinical significance of urinary protein markers in DN patients and the interventional effects of Chinese herbal medicine.

Characteristic of urinary protein spectrum in patients with stage III diabetic nephropathy and its regression analysis with traditional Chinese medicine symptom / 中国中药杂志

To analyze the characteristic of urinary protein spectrum in patients with stage III diabetic nephropathy (DN) and its compliance with traditional Chinese medicine (TCM)symptom, for the sake of providing a basis for clarifying the rules of TCM syndrome differentiation in DN. Adopting the traditional epidemiological retrospective method, thirty-eight TCM syndromes and urinary protein with medium or low molecular weight, as well as urinary enzyme, including 24 h urinary protein (Upro), urinary albumin( UAlb), urinary retinal binding protein( URBP), urinary cystatin C (UCysC), urinary N-acetyl-beta-D-glucosaminidase (UNAG), were collected from 108 patients with stage III DN, and a multiple factor regression analysis between them was conducted. As the results, the levels of Upro, UAlb, URBP, UCysC, and UNAG were increased in 108 patients with stage III DN. Qi-Yin deficiency type was the major type. The level of UAlb in patients with Qi-Yin deficiency type was significantly higher than those without Qi-Yin deficiency type (P < 0.05). The elevation of Upro with the factors as swift digestion with rapid hungering, lassitude and lack of strength, weakness of waist and knees was complied, the elevation of UA1b with the factors as dry mouth with desire to drink, the elevation of URBP with the factors as numbness of extremities, shortness of breath, the elevation of UCysC with the factors as clear urine in large amounts, and the elevation of UNAG with the factors as frequent micturition, were complied respectively. In conclusion, for 108 stage III DN patients. The increase in urinary protein spectrum including UAlb, URBP, UCysC, and UNAG is the major characteristic. Shen and Pi are the major organs related to the appearance of urinary protein; Pi-Shen deficiency is the basic pathogenesis. The level of UAlb is taken as one of the objective syndrome factors for Qi-Yin deficiency type. The levels of UNAG and UCysC are possibly the objective syndrome factors for Shen-Qi deficiency type.

Effects of strophanthidin on intracellular calcium concentration in ventricular myocytes of guinea pig / 药学学报

Effect of strophanthidin (Str) on intracellular calcium concentration ([Ca2+]i) was investigated on isolated ventricular myocytes of guinea pig. Single ventricular myocytes were obtained by enzymatic dissociation technique. Fluorescent signal of [Ca2+]i was detected with confocal microscopy after incubation of cardiomycytes in Tyrode' s solution with Fluo3-AM. The result showed that Str increased [Ca2+]i in a concentration-dependent manner. The ventricular myocytes began to round-up into a contracture state once the peak level of [Ca2+]i was achieved in the presence of Str (10 micromol L(- 1)), but remained no change in the presence of Str (1 and 100 nmol L(-1)). Tetrodotoxin (TTX), nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str (1 and 100 nmol L(-1)) , but had no obvious effects on the action of Str (10 micromol L(-1)). The elevation of [Ca2+]i caused by Str at all of the detected concentrations was partially antagonized by rynodine (10 micromol L(-1)) or the removal of Ca2+ from Tyrode's solution. In Na+, K+ -free Tyrode' s solution, the response of cardiomycytes in [Ca2+]i elevation to Str (10 micromol L(-1)) was attenuated, while remained no change to Str (1 and 100 nmol L(-1)). TTX, nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str at all of the detected concentrations in Na+, K+ -free Tyrode's solution. The study suggests that the elevation of [Ca2+]i by Str at the low (nomomolar) concentrations is partially mediated by the extracellular calcium influx through Ca2+ channel or a "slip mode conductance" of TTX sensitive Na+ channel. While the effect of Str at high (micromolar) concentrations was mainly due to the inhibition of Na+, K+ -ATPase. Directly triggering the release of intracellular Ca2+ from sarcoplasmic reticulum (SR) by Str may be also involved in the mechanism of [Ca2+]i elevation.

Involvement of nuclear factor of activated T-cells (NFATc) in calcineurin-mediated ischemic brain damage in vivo / 药学学报

<p><b>AIM</b>To study the involvements of nuclear factor of activated T-cells (NFATc) and NF-kappaB in calcineurin-mediated ischemic brain damage in vivo.</p><p><b>METHODS</b>The rat transient forebrain ischemia conducted through 15 min ischemia followed by 8, 24, and 72 h reperfusion was induced using the four-vessel method. The rats were divided randomly into five groups; sham control group, ischemia/reperfusion (I/R) group, CsA treated groups (for 8, 24, and 72 h reperfusion). Western blotting was performed to detect changes of FasL, NFATc, I-kappaB-alpha, and phospho-I-kappaB-alpha protein expression, and gel shift assays for NFAT FasL-DNA binding activities.</p><p><b>RESULTS</b>Western blotting showed that the expressions of both FasL and NFATc protein were significantly increased in the hippocampus of rat subjected to transient forebrain ischemia in comparison with those of the sham control group, which were markedly reduced by CsA. The I-kappaB-alpha protein showed no changes in all groups, and phospho-I-kappaB-alpha protein was not observed in this study. Proximal and distal FasL promoter NFAT sites bind NFAT proteins from the hippocampal neurons subjected to transient forebrain ischemia, and DNA-binding activities increased significantly compared with those of the sham control group. CsA markedly inhibited these changes.</p><p><b>CONCLUSION</b>NFATc may be involved in calcineurin-mediated ischemic brain damage and transcription factor NF-kappaB may not be involved.</p>

Virological and immunological outcomes in HIV-1-infected Chinese patients treated with a combination of Efavirenz and Indinavir for 48 weeks / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The incidence of HIV-1-related infection diseases and the mortality of AIDS have dramatically decreased since highly active antiretroviral therapy began to be used clinically in China in 1999. And we initiated a second clinical trial using a combination of Efavirenz and Indinavir to observe the effects of the immunoreaction.</p><p><b>METHODS</b>Twenty patients with laboratory-confirmed chronic HIV-1 infection were recruited. Blood samples were collected initially and during the weeks after initiation of treatment. Within 48 hours of blood sampling, peripheral blood plasma and mononuclear cells were separated using routine methods. HIV-1 viral load was measured in thawed plasma samples. Within 48 hours of peripheral blood sampling, CD4(+) and CD8(+) T cell subsets were enumerated.</p><p><b>RESULTS</b>The drug regimen was efficient in reducing HIV-1 plasma viral load and increasing total CD4(+) T cell counts. The percentage of CD4(+) and CD8(+) T cell subsets expressing CD38 and HLA-DR activation markers was positively correlated with plasma viral load and tended to normalize.</p><p><b>CONCLUSIONS</b>The combination of Efavirenz and Indinavir was generally well tolerated and efficient at reducing HIV-1 RNA. Furthermore, the treatment improved the immunological function.</p>

Study on the distribution of human immunodeficiency virus-1 subtypes in different regions of China and mother-to-child transmission / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the distribution of human immunodeficiency virus (HIV)-1 genotypes in major prevalent regions of China and to illustrate the relationship between HIV-1 subtypes and mother-to-child transmission in a retrospective cohort.</p><p><b>METHODS</b>HIV-1 gag p17 and env C2-V4 region were amplified by nested-polymerase chain reaction (nPCR) and the sequences were obtained by sequencing gag nPCR products or clones of env gene.</p><p><b>RESULTS</b>60 HIV-1 positive individuals were subject to typing for gag p17 and 69 for env C2-V4 region. Single clade was only found in Henan (subtype B') and Xinjiang (subtype C), and subtypes C and E were demonstrated in Yunnan. These regions represented most of the HIV-1 infections in China. Multiple subtypes (A, B, C, E, etc.) were found in Beijing and Shanghai, where HIV infections were still in low level. The sequences of subtype C were less diversive in Xinjiang (p17: 0.0192 +/- 0.0078, C2-V4: 0.0455 +/- 0.0145) than in Yunnan (p17: 0.0279 +/- 0.0102, C2-V4: 0.0482 +/- 0.0171), but all of them clustered in "C" branch in phylogenetic trees. Trafficking of subtype C from Yunnan to Xinjiang was found but had already been reported by others. Compared to subtype C, subtype E was quite divergent (p17: 0.0473 +/- 0.0105, C2-V4: 0.1114 +/- 0.0112) in Yunnan, but no recombination was found in the C2-V4 region of env gene. Highe divergence of subtype B' was found in Henan and the peripheral provinces (p17: 0.0381 +/- 0.0101, C2-V4: 0.0691 +/- 0.0166), which might be attributed to the early epidemics of HIV-1 in these areas (early 1990's). In maternal-child cohort, subtypes B (7/21), C (11/21), E (1/21) and undefined types (2/21) were identified in non-transmitting HIV-1 positive mothers, while only subtype B (7/11) and C (4/11) appeared in transmitting HIV-1 positive mothers. The rate of transmission was 53.8% (7/13) in mothers infected with subtype B and 30.8% (4/13) in those infected with subtype C, but with no significant difference (P = 0.196). The imbalancing distribution of subtypes might be explained by the fact that transfusion or illegal blood would increased mother-to-child transmission on HIV-1 and most of mothers with clade B were infected by illegal blood transfusion in this cohort. In addition, most of the maternal-child pair's sequences clustered in gag or env phylogenetic trees but only a few did disperse among the unrelated patients because children were older (>/= 4 years).</p><p><b>CONCLUSION</b>The characteristics of HIV-1 clade's distribution differed over most parts of China but no difference was demonstrated between subtype B and C in mother-to-child transmission on HIV-1.</p>

Study on the epidemiology and distribution of human immunodeficiency virus-1 and hepatitis C virus infection among intravenous drug users and illegal blood donors in China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To determine the epidemiologic features and distribution of human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) infection among intravenous drug users and illegal blood donors in China.</p><p><b>METHODS</b>Polymerase chain reaction (PCR) amplification and DNA sequencing were used to evaluate the HIV-1 gag p17 and env C2-V3 regions, as well as the HCV 5'NCR and E1/E2 regions.</p><p><b>RESULTS</b>Among 239 subjects with reported HIV-1 infection, 56.9% (136/239) were seropositive for anti-HCV. Of those, 96.3% (131/136) were co-infected with HCV through intravenous drug use and illegal blood donation. Intravenous drug users in Yunnan, Guangxi and Xinjiang provinces were infected with HIV-1 subtype C and HCV genotypes 1b, 3a, 3b and 4, whereas illegal blood donors in Henan province harbored HIV-1 subtype B' and HCV genotypes 1b and 2a. Five different HIV-1 subtypes were identified among 17 HIV-1-infected individuals from Beijing.</p><p><b>CONCLUSIONS</b>Multiple HIV-1 subtypes and HCV genotypes were identified in China which were associated with several different modes of transmission. Homogeneity within the sequences of the two viruses suggested the recent, but separate, outbreaks of HIV-1 and HCV infection. The distinct distribution patterns of HIV-1 and HCV genotypes in two high-risk groups seemed to be more closely linked to the mode of transmission than to geographic proximity.</p>