The Relationship Between Serum Netrin-1 Expression Levels and Prognosis in Revascularized Patients with Acute Ischemic Stroke.

BACKGROUND: This study aimed to explore the relationship between serum netrin-1 expression levels and acute prognosis in patients with acute ischemic stroke (AIS) within 24 hours after revascularization. METHODS: A total of 121 revascularized patients admitted to the Jinshan Branch of the Shanghai Sixth People's Hospital, China, between July 2019 and July 2021 were selected as study subjects. The primary outcome was the modified Rankin Scale (mRS) score three months after revascularization: patients with an mRS score >2 were classified into the unfavorable prognosis group and others into the favorable prognosis group. Those with serum netrin-1 expression levels greater than the median of all patients were classified into the elevated protein group and others into the decreased protein group. Multivariate logistic regression analysis was used to analyze the independent risk factors for prognosis in patients with AIS after revascularization. RESULTS: The differences between the unfavorable prognosis group and the favorable prognosis group in gender, age, coronary heart disease, and netrin-1 levels were not statistically significant (p > 0.05). However, the National Institute of Health Stroke Scale (NIHSS) scores and number of patients with comorbid hypertension in the unfavorable prognosis group were significantly higher than in the favorable prognosis group (p < 0.05). Multivariate logistic regression analysis showed that NIHSS score before revascularization was an independent risk factor for unfavorable prognosis but that netrin-1 expression levels were not significantly associated with prognosis in patients after revascularization. CONCLUSIONS: Serum netrin-1 expression levels in the acute phase are not significantly associated with prognosis in patients with AIS after revascularization.

Effect of Huangkui on mouse podocytes under high glucose environment / Efecto de Huangkui en podocitos de ratón en un entorno de glucosa alta

To explore a new underlying molecular mechanism of Huangkui Extract Powder (HKEP) in the alleviation of diabetic nephropathy (DN). Murine immortalized podocytes were divided into (i) normal glucose (NG, 5.6 mM), (ii) NG + HKEP (0.45 g/L), (iii) HG, and (iv) HG + HKEP (0.45 g/L) groups. MTT assay and flow cytometry were used to detect the podocyte proliferation, apoptosis and cell cycle. Cell viability was inhibited, and apoptosis increased in(iii) HG group compared with (i) NG group (p<0.05). mRNA and protein expression of nephrin and podocin significantly decreased in (iii) HG group compared with (i) NG group (p<0.05). When compared with (iii) HG group, (iv) HG + HKEP group had higher cell viability, lower apoptotic rate and higher mRNA and protein expression of nephrin and podocin (p<0.05). HKEP can attenuate HG-induced podocyte damage, which may be one of the mechanisms of HKEP for attenuating DN.

Explorar un nuevo mecanismo molecular subyacente del extracto del polvo de Huangkui (HKEP) en el alivio de la nefropatía diabética (ND). Los podocitos murinos inmortalizados se dividieron en (i) grupos de glucosa normal (NG, 5,6 mM), (ii) NG + HKEP (0,45 g/L), (iii) HG y (iv) HG + HKEP (0,45 g/L). Se utilizaron el ensayo MTT y la citometría de flujo para detectar la proliferación de podocitos, la apoptosis y el ciclo celular. La viabilidad celular se inhibió y la apoptosis aumentó en el grupo (iii) HG en comparación con el grupo (i) NG (p<0,05). La expresión de ARNm y proteínas de nefrina y podocina disminuyó significativamente en el grupo (iii) HG en comparación con el grupo (i) NG (p<0,05). En comparación con el grupo (iii) HG, el grupo (iv) HG + HKEP tuvo una mayor viabilidad celular, una tasa de apoptosis más baja y una expresión de ARNm y proteínas más altas de nefrina y podocina (p<0,05). HKEP puede atenuar el daño de los podocitos inducido por HG, que puede ser uno de los mecanismos de HKEP para atenuar la DN.

Verification of SARS-CoV-2-Encoded small RNAs and contribution to Infection-Associated lung inflammation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. SARS-CoV-2 is a positive-stranded RNA virus belongs to Coronaviridae family. The viral genome of SARS-CoV-2 contains around 29.8 kilobase with a 5'-cap structure and 3'-poly-A tail, and shows 79.2% nucleotide identity with human SARS-CoV-1, which caused the 2002-2004 SARS outbreak. As the successor to SARS-CoV-1, SARS-CoV-2 now has circulated across the globe. There is a growing understanding of SARS-CoV-2 in virology, epidemiology, and clinical management strategies. In this study, we verified the existence of two 18-22 nt small viral RNAs (svRNAs) derived from the same precursor in human specimens infected with SARS-CoV-2, including nasopharyngeal swabs and formalin-fixed paraffin-embedded (FFPE) explanted lungs from lung transplantation of COVID-19 patients. We then simulated and confirmed the formation of these two SARS-CoV-2-Encoded small RNAs in human lung epithelial cells. And the potential pro-inflammatory effects of the splicing and maturation process of these two svRNAs in human lung epithelial cells were also explored. By screening cytokine storm genes and the characteristic expression profiling of COVID-19 in the explanted lung tissues and the svRNAs precursor transfected human lung epithelial cells, we found that the maturation of these two small viral RNAs contributed significantly to the infection associated lung inflammation, mainly via the activation of the CXCL8, CXCL11 and type I interferon signaling pathway. Taken together, we discovered two SARS-CoV-2-Encoded small RNAs and investigated the pro-inflammatory effects during their maturation in human lung epithelial cells, which might provide new insight into the pathogenesis and possible treatment options for COVID-19.

Research progress on mechanisms of monomer ingredients of Chinese materia medica anti-tumor invasion and metastasis / 药物评价研究

As the essential characteristics of malignant cancer,invasion and metastasis are the main reason for failure treatment and high death rate of cancer patients.It is necessary to find out safe and effective anti-invasion and anti-metastasis drugs for the improvement of clinical efficacy.With the definite therapeutic effect and mild side-effects,Chinese materia medica(CMM) including curcumin,peiminine,β-elemi and so on,have become hotspots in anti-invasion and anti-metastasis drugs research.The mechanisms for the effective ingredients of CMM anti-tumor invasion and metastasis were reviewed in this paper.

Effects of luteolin on invasion, migration and adhesion of human hepatocellular carcinoma HepG2 cells / 中国病理生理杂志

AIM:To investigate the effects of luteolin on invasion,migration and adhesion of human hepatocelluar carcinoma HepG2 cells.METHODS:HepG2 cells were cultured and treated with luteolin at 10,20 and 40 μmol/L respectively.The invasion capability was examined by cell invasion assay.The migration ability was examined by wound healing assay.The adhesion capability was measured by adhesion assay.The protein levels of E-cadherin,N-cadherin,vimentin and Snai1 were determined by Western blot analysis.RESULTS:Luteolin inhibited the invasion,migration and adhesion ability of HepG2 cells in vitro in a dose-dependent manner.After treatment with luteolin,the expression of E-cadherin was increased significantly and the expression of N-cadherin,vimentin and Snai1 were decreased significantly.CONCLUSION:Luteolin inhibits the invasion,migration and adhesion ability of human hepatocelluar carcinoma HepG2 cells.The mechanism may be related to the regulatory effects of luteolin on epithelial-mesenchymal transition.

Research progress on mechanisms of monomer ingredients of Chinese materia medica anti-tumor invasion and metastasis / 药物评价研究

As the essential characteristics of malignant cancer,invasion and metastasis are the main reason for failure treatment and high death rate of cancer patients.It is necessary to find out safe and effective anti-invasion and anti-metastasis drugs for the improvement of clinical efficacy.With the definite therapeutic effect and mild side-effects,Chinese materia medica(CMM) including curcumin,peiminine,β-elemi and so on,have become hotspots in anti-invasion and anti-metastasis drugs research.The mechanisms for the effective ingredients of CMM anti-tumor invasion and metastasis were reviewed in this paper.

Effects of luteolin on invasion, migration and adhesion of human hepatocellular carcinoma HepG2 cells / 中国病理生理杂志

AIM:To investigate the effects of luteolin on invasion,migration and adhesion of human hepatocelluar carcinoma HepG2 cells.METHODS:HepG2 cells were cultured and treated with luteolin at 10,20 and 40 μmol/L respectively.The invasion capability was examined by cell invasion assay.The migration ability was examined by wound healing assay.The adhesion capability was measured by adhesion assay.The protein levels of E-cadherin,N-cadherin,vimentin and Snai1 were determined by Western blot analysis.RESULTS:Luteolin inhibited the invasion,migration and adhesion ability of HepG2 cells in vitro in a dose-dependent manner.After treatment with luteolin,the expression of E-cadherin was increased significantly and the expression of N-cadherin,vimentin and Snai1 were decreased significantly.CONCLUSION:Luteolin inhibits the invasion,migration and adhesion ability of human hepatocelluar carcinoma HepG2 cells.The mechanism may be related to the regulatory effects of luteolin on epithelial-mesenchymal transition.

Sensitivity of Plasmodium falciparum to Antimalarial Drugs in Hainan Island, China

Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time (22.5+/-10.6 hr) and the mean parasite clearance time (27.3+/-12.2 hr) showed no statistical significance with different genders, ages, temperatures, or parasite density (P>0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (Ppiperaquine>pyronarididine>artesunate. The inhibitory dose 50 (IC50) was 3.77x10(-6) mol/L, 2.09x10(-6) mol/L, 0.09x10(-6) mol/L, and 0.05x10(-6) mol/L, and the mean concentrations for complete inhibition (CIMC) of schizont formation were 5.60x10(-6) mol/L, 9.26x10(-6) mol/L, 0.55x10(-6) mol/L, and 0.07x10(-6) mol/L, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.

Sensitivity of Plasmodium falciparum to Antimalarial Drugs in Hainan Island, China

Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time (22.5+/-10.6 hr) and the mean parasite clearance time (27.3+/-12.2 hr) showed no statistical significance with different genders, ages, temperatures, or parasite density (P>0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (Ppiperaquine>pyronarididine>artesunate. The inhibitory dose 50 (IC50) was 3.77x10(-6) mol/L, 2.09x10(-6) mol/L, 0.09x10(-6) mol/L, and 0.05x10(-6) mol/L, and the mean concentrations for complete inhibition (CIMC) of schizont formation were 5.60x10(-6) mol/L, 9.26x10(-6) mol/L, 0.55x10(-6) mol/L, and 0.07x10(-6) mol/L, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.

Correlation between tag single nucleotide polymorphisms of microRNA regulatory genes and the genetic susceptibility of primary liver cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>This study aimed to understand the correlation between tag single nucleotide polymorphisms (tSNP) of microRNA regulatory genes and the gentic susceptibility of primary liver cancer.</p><p><b>METHODS</b>1:1 case-control study was applied in this research. A total of 532 primary liver cancer patients in 2 teaching hospitals in Zhengzhou city were enrolled as case group.532 healthy individuals were enrolled as control group. The subjects were surveyed by a face-to-face interview and 5 ml of peripheral venous blood were collected. Candidate tSNP were screened from DICER1, RAN and GEMIN4 gene, respectively. PCR-RFLP or Allele specific PCR was applied for genotyping of the subjects. Conditional logistic regression model and Multifactor-Dimensionality Reduction method were applied for analyzing the correlation between tSNP of above genes and gentic susceptibility of primary liver cancer. The gene-environment interaction was also analyzed.</p><p><b>RESULTS</b>The frequencies of genotype CC, CT, TT in rs14035 locus were 67.29% (358/532), 28.20% (150/532), 4.51% (24/532) in case group, and 70.30% (374/532), 28.20% (150/532), 1.50% (8/532) in control group, respectively (χ2=8.35, P<0.05). The frequencies of genotype GG, GA, AA in rs1045491 locus were 71.05% (378/532), 26.69% (142/532), 2.26% (12/532) in case group, and 80.45% (428/532), 18.42% (98/532), 1.13% (6/532) in control group, respectively (χ2=13.17, P<0.01); the frequencies of genetype GG, GT, TT in rs2291778 locus were 53.38% (284/532), 40.23% (214/532), 6.39% (34/532) in case group, and were 25.94% (138/532), 63.91% (340/532), 10.15% (54/532) in control group (χ2=83.71, P<0.01). TT genotype in rs14035 locus (OR=2.54, 95%CI: 1.19-6.32) and GA genetype in rs1045491 locus (OR=1.74, 95%CI: 1.08-2.66) were susceptible genotype of primary liver cancer, whereas GT (OR=0.52, 95%CI: 0.43-0.75) and TT genotype (OR=0.62, 95%CI: 0.46-0.86) in rs2291778 locus were protective genotype. Haplotype analysis showed that haplotype 3 (AACTGGGT) (OR=1.42, 95%CI: 1.10-1.82) and haplotype 5 (AGCCAGCC) increased the risk of occurrence of primary liver cancer (OR=1.36, 95%CI: 1.02-1.80), whereas haplotype 2 (AACTATCC) (OR=0.69, 95%CI: 0.52-0.91) and haplotype 6 (AACTGTGT)(OR=0.61, 95%CI: 0.45-0.81) decreased the risk. Subjects exposed to allele A of rs1045491, allele T of rs14035 and HBV infection intend to be the high risk population of primary liver cancer (OR = 3.72, 95%CI: 2.38 - 5.56).</p><p><b>CONCLUSION</b>Genotypes of TT in rs14035 locus, and GA in rs1045491 locus may be susceptible genotypes of liver cancer carcinogenesis. T allele in rs2291778 locus is a non-susceptible allele of primary liver cancer. Combined effects of multigene alleles and multi-locus genotype may have a synergistic role in the carcinogenesis of liver cancer.</p>

Development of a SPA-ELISA method for detecting anti-coronavirus IgG antibodies in serum samples from fulvous fruit bats / 南方医科大学学报

<p><b>OBJECTIVE</b>To develop an simple and sensitive method for detecting anti-coronavirus IgG antibodies in bat sera based on enzyme-linked immunosorbent assay (ELISA).</p><p><b>METHODS</b>A commercial ELISA kit for detecting SARS-CoV antibody was modified for detecting coronavirus antibodies in bat serum samples. The second antibody in the kit was replaced with horseradish peroxidase-conjugated protein-A (HRP-SPA) based on the characteristics of binding between Staphylococcus aureus protein A (SPA) and mammal IgG Fc fragment. The sera of 55 fulvous fruit bats (Rousettus dasymallus) were tested using the SPA-ELISA.</p><p><b>RESULTS</b>The test results of the positive and negative controls in the kit and the serum samples from convalescent ;patient were consistent with expectation. Coronavirus antibody was detected in 2 out of the 55 bat serum samples. Serum neutralization test confirmed the validity of the SPA-ELISA method.</p><p><b>CONCLUSION</b>This SPA-ELISA method is applicable for detecting coronavirus antibody in bat sera.</p>

[Percutaneous transluminal angioplasty in treatment of lower limb peripheral arterial disease in diabetes patients: analysis of 150 cases].

OBJECTIVE: To analyze the technical success rate and short-term clinical results of percutaneous transluminal angioplasty (PTA) in treatment of lower limb peripheral arterial disease (PAD) in diabetes mellitus (DM) patients. METHODS: 150 consecutive DM patients PAD (176 limbs) with Fontaine degree I - IV were treated with PTA and followed up for 5 months (1 - 16 months). The result with the residual stenosis < 30% was regarded as success. RESULTS: Totally 187 PTA procedures were performed in 150 patients (176 limbs) with a technical success rate of 91.4% (161/176)). No serious complication occurred. The clinical symptoms of all patients improved after successful PTA. The median ankle-brachial index (ABI) marginally increased from the baseline value of 0.34 +/- 0.27 to 0.96 +/- 0.24 after intervention. The ABI levels 1 month and 6 months after PTA were 0.88 +/- 0.34 and 0.71 +/- 0.26 respectively. The cumulative restenosis rate was 13.7%, and the reintervention rate was 7.2%. CONCLUSION: With high success rate, low complication rate, and sure curative effect, PTA can be performed as the first choice in treatment of the lower limb PAD in DM patients.

[Effects of Refined Xuefu Capsule on vascular patency rate after femoral-popliteal bypass].

OBJECTIVE: To observe the effects of refined Xuefu Capsule (RXC) in patients with arteriosclerosis obliterans (ASO) after femoral-popliteal bypass (FPB). METHODS: Thirty-eight ASO patients with 41 limbs underwent FPB were randomly assigned to two groups: the control group (18 cases with 20 operated limbs) and the RXC group (20 cases with 21 operated limbs). All patients received long-term anticoagulant treatment with Warfarin, and RXC was given to the RXC group additionally for 3 months. Changes of clinical symptoms, blood coagulating function, as well as the condition of vascular patency and ankle arm index (AAI) were assessed 6 and 12 months after operation. RESULTS: Clinical symptoms were improved in all the patients after operation. One year after operation, incidence of intermittent claudication and amputation rate in the RXC group was 20% and 5 %, being lower than the respective rate (56% and 17%) in the control group (P < 0.05); the patency rate was 86% in the RXC group, being higher than that in the control group (65%, P<0.05). Six and 12 months after operation, AAI was 0.73 +/- 0.24 and 0.69 +/- 0.19 respectively in the RXC group, being significantly higher than that in the control group (0.45 +/- 0.17 and 0.41 +/- 0.23, P < 0.05) at the corresponding time points. CONCLUSION: RXC could obviously increase the patency rate 12 months after FPB, improve the clinical symptoms and alleviate the symptom of limb ischemia in ASO patients.

Newborn screening of inherited metabolic diseases by tandem mass spectrometry.

Application of TMS technology in newborn screening has resulted in major expansion of disorder panel for metabolic diseases in recent years. This automated, multiplex testing methodology detects multiple analytes from single analysis of one blood spot, which leads to detection of 30-35 disorders of amino acids, organic acids, and fatty acids metabolism. The early identification of persons affected with inborn errors of metabolism has led to unexpected discoveries related to the natural history of the disorder or options for therapy. This article summarized (1) the basic principles of this technology and methodology. (2) Current status of application of this methodology in the United States, European countries and in China. (3) The positive impacts on the public health and advances in medical genetics. Finally (4) Challenges, issues and possible solutions. The purpose of this article aimed at introducing new technology and exploring the possibilities of implementing into developing countries where medical genetics is not developed and foreseeing the possible problems and obstacles.

Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content.

To examine the mechanism by which fish oil protects against fat-induced insulin resistance, we studied the effects of control, fish oil, and safflower oil diets on peroxisomal content, fatty acyl-CoA, diacylglycerol, and ceramide content in rat liver and muscle. We found that, in contrast to control and safflower oil-fed rats, fish oil feeding induced a 150% increase in the abundance of peroxisomal acyl-CoA oxidase and 3-ketoacyl-CoA thiolase in liver but lacked similar effects in muscle. This was paralleled by an almost twofold increase in hepatic peroxisome content (both P < 0.002 vs. control and safflower). These changes in the fish oil-fed rats were associated with a more than twofold lower hepatic triglyceride/diacylglycerol, as well as intramuscular triglyceride/fatty acyl-CoA, content. In conclusion, these data strongly support the hypothesis that n-3 fatty acids protect against fat-induced insulin resistance by serving as peroxisome proliferator-activated receptor-alpha ligands and thereby induce hepatic, but not intramuscular, peroxisome proliferation. In turn, an increased hepatic beta-oxidative capacity results in lower hepatic triglyceride/diacylglycerol and intramyocellular triglyceride/fatty acyl-CoA content.