Visualized analysis of research hotspots of the treatment of diabetic retinopathy based on CiteSpace and VOSviewer / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the current status, hotspots and trends of studies on the treatments of diabetic retinopathy.METHODS: Relevant literatures on diabetic retinopathy in Chinese National Knowledge Infrastructure(CNKI)and Web of Science core collection database were retrieved from creation to June 15, 2023, and CiteSpace 6.2.R2 and VOSviewer were used to conduct visualized analysis with the country/issuing institution, research author and keywords.RESULTS: A total of 5 919 Chinese literatures and 11 475 English literatures were included. The top three countries with global publications are the United States, China and the United Kingdom, respectively. The top three institutions for issuing articles at abroad are Harvard Medical School, Harvard University and Johns Hopkins University, while the top three institutions for issuing articles in China are the Eye Hospital of China Academy of Chinese Medical Science, Hunan University of Chinese Medicine, and Zhongshan Ophthalmic Center of Sun Yat-sen University. The research results of high-frequency keywords in both Chinese and English show that the laser photocoagulation, vitrectomy, traditional Chinese medicine therapy, vascular endothelial growth factor and ranibizumab are research hotspots.CONCLUSIONS: In recent years, the research hotspots of diabetic retinopathy mainly focus on surgery, vascular protective agents, traditional Chinese medicine therapy, anti-vascular endothelial growth factor, etc., and the research trend mainly focuses on anti-vascular endothelial growth factor drugs.

Diagnostic value of cross-primer isothermal amplification technology in tuberculosis and its related influencing factors / 中国热带医学

@#Abstract： Objective　To analyze the value and influencing factors of cross-primer isothermal amplification technology(CPA) in clinical screening and diagnosis of tuberculosis (TB). Methods　We collected 543 inpatients in the Second Affiliated Hospital of Hainan Medical College from January 1, 2018 to December 31, 2021, including 179 patients with tuberculosis, 187 patients with pneumonia and 177 patients with other diseases. The patients' sputum, alveolar lavage fluid, pleural effusion and midstream urine were detected by CPA, smear microscopy, culture method and gene detection. The value of CPA detection in the diagnosis of tuberculosis and its influencing factors were evaluated. Statistical analysis was performed using SPSS 26.0. Results　The total positive rate of CPA was 14.4% (78/543), and the positive rate of sputum samples accounted for 29.1% (39/134). Among the 78 cases of CPA positive patients, the tuberculosis group accounted for 69.2% (54/78), followed by pneumonia group 21.8% (17/78), and other diseases group accounted for 9.0% (7/78). Taking CPA test as the reference method, the "sensitivity" of smear microscopy was lower than that of genetic testing and culture, while the "specificity" was higher than that of culture and gene testing, and the "missed diagnosis rate" of smear microscopy was higher than that of genetic testing and culture. CPA test positive was related to gender, ESR and pneumonia. There is a good agreement between CPA test and culture method and gene test (Kappa>0.9), and a moderate agreement between CPA test and smear microscopy (Kappa=0.616). Conclusions　Sputum specimen is the best choice for CPA detection, while the value of pleural effusion detection is relatively limited. Sputum, alveolar lavage fluid and midcourse urine can be used as clinical specimens for screening and diagnosis of "tuberculosis group and other disease group", while sputum can be used for screening and diagnosis of "tuberculosis group and pneumonia group". Gender, ESR and pneumonia are the influencing factors of CPA positive patients. Therefore, CPA testing is worthy of clinical promotion, but more clinical research data are needed.

Preparing for and conducting the National Health and Morbidity Survey in Malaysia amid the COVID-19 pandemic: balancing risks and benefits to participants and society

@#Problem: The novel coronavirus disease 2019 (COVID-19) pandemic adversely affected the preparation of Malaysia’s National Health and Morbidity Survey for 2020 because conducting it would expose data collectors and participants to an increased risk of infection. Context: The survey is nationally representative and community based and is conducted by the Institute for Public Health, part of the National Institutes of Health, to generate health-related evidence and to support the Malaysian Ministry of Health in policymaking. Its planned scope for 2020 was the seroprevalence of communicable diseases such as hepatitis B and C. Action: Additional components were added to the survey to increase its usefulness, including COVID-19 seroprevalence and facial anthropometric studies to ensure respirator fit. The survey’s scale was reduced, and data collection was changed from including only face-to-face interviews to mainly self-administered and telephone interviews. The transmission risk to participants was reduced by screening data collectors before the survey and fortnightly thereafter, using standard droplet and contact precautions, ensuring proper training and monitoring of data collectors, and implementing other administrative infection prevention measures. Outcome: Data were collected from 7 August to 11 October 2020, with 5957 participants recruited. Only 4 out of 12 components of the survey were conducted via face-to-face interview. No COVID-19 cases were reported among data collectors and participants. All participants were given their hepatitis and COVID-19 laboratory test results; 73 participants with hepatitis B and 14 with hepatitis C who had been previously undiagnosed were referred for further case management. Discussion: Preparing and conducting the National Health and Morbidity Survey during the COVID-19 pandemic required careful consideration of the risks and benefits, multiple infection prevention measures, strong leadership and strong stakeholder support to ensure there were no adverse events.

Comorbidities and clinical features related to severe outcomes among COVID-19 cases in Selangor, Malaysia

@#Background: Pre-existing comorbidities can predict severe disease requiring intensive care unit (ICU) admission among COVID-19 cases. We compared comorbidities, clinical features and other predictive factors between COVID-19 patients requiring ICU admission for intubation/mechanical ventilation and all other COVID-19 cases in Selangor, Malaysia. Methods: Field data collected during the COVID-19 outbreak in Selangor, Malaysia, up to 13 April 2020 were used, comprising socio-demographic characteristics, comorbidities and presenting symptoms of COVID-19 cases. ICU admission was determined from medical records. Multiple logistic regression analysis was performed to identify factors associated with ICU admission requiring intubation/mechanical ventilation among COVID-19 cases. Results: A total of 1287 COVID-19-positive cases were included for analysis. The most common comorbidities were hypertension (15.5%) and diabetes (11.0%). More than one third of cases presented with fever (43.8%) or cough (37.1%). Of the 25 cases that required intubation/mechanical ventilation, 68.0% had hypertension, 88.0% had fever, 40.0% had dyspnoea and 44.0% were lethargic. Multivariate regression showed that cases that required intubation/mechanical ventilation had significantly higher odds of being older (aged 360 years) [adjusted odds ratio (aOR) = 3.9] and having hypertension (aOR = 5.7), fever (aOR = 9.8), dyspnoea (aOR = 9.6) or lethargy (aOR = 7.9) than cases that did not require intubation/mechanical ventilation. Conclusion: The COVID-19 cases in Selangor, Malaysia requiring intubation/mechanical ventilation were significantly older, with a higher proportion of hypertension and symptoms of fever, dyspnoea and lethargy. These risk factors have been reported previously for severe COVID-19 cases, and highlight the role that ageing and underlying comorbidities play in severe outcomes to respiratory disease.

The regulation of retinoid X receptor-mediated oxidative stress pathway in rat pulmonary ischemia/reperfusion injury / 生理学报

The aim of this study was to investigate the regulatory role of retinoid X receptor (RXR)-mediated oxidative stress pathway in rat pulmonary ischemia/reperfusion injury (PIRI) and the underlying mechanism. Seventy-seven male Sprague-Dawley (SD) rats were randomly divided into 7 groups (n = 11): control group, sham group, sham+9-cis-retinoid acid (9-cRA, RXR agonist) group, sham+HX531 (RXR inhibitor) group, ischemia/reperfusion (I/R) group, I/R+9-cRA group, and I/R+HX531 group. The unilateral lung I/R model was established by obstruction of left lung hilus for 30 min and reperfusion for 180 min in vivo. The rats in I/R+9-cRA and I/R+HX531 groups were given intraperitoneal injection of 9-cRA and HX531 before thoracotomy. After reperfusion, the left lung tissue was taken to evaluate the lung tissue injury, and the oxidative stress-related indexes of the lung tissue were detected by the corresponding kits. The lung tissue morphology and the ultrastructure of the alveolar epithelial cells were observed by HE staining and transmission electron microscope, respectively. The protein expression of RXR in lung tissue was observed by immunofluorescence labeling method, and the expression level of nuclear factor E2-related factor (Nrf2) protein was detected by Western blot. The results showed that, compared with the sham group, the I/R group exhibited obviously injured lung tissue, decreased SOD activity, increased MDA content and MPO activity, and down-regulated expression level of Nrf2 protein. Compared with the I/R group, the I/R+9-cRA group showed alleviated lung tissue injury, increased activity of SOD, decreased MDA content and MPO activity, and up-regulated expression levels of RXR and Nrf2 protein. The above-mentioned improvement effects of 9-cRA were reversed by HX531 treatment. These results suggest that RXR activation can effectively protect the lung tissue against I/R injury, and the mechanism may involve the activation of Nrf2 signaling pathway, the enhancement of antioxidant level and the reduction of oxidative stress response.

Study on wavelength overlapping HPLC fingerprint and multi-component content determination of Danshen / 中国中药杂志

This project was launched to and establish the wavelength overlapping HPLC fingerprint for Danshen and determine the contents of 7 component in Danshen. The chromatographic fingerprints were built by using Agilent Eclipse Plus C_(18)( 4. 6 mm×100 mm,3. 5 μm) as stationary phase and 0. 1% formic acid solution( A)-acetonitrile( B) as mobile phase with gradient elution( 0-5 min,10%-20% B; 5-20 min,20%-30% B; 20-25 min,30%-50% B; 25-40 min,50%-65% B; 40-45 min,65%-80% B; 45-46 min,80%-10% B; 46-50 min,10% B) at a flow rate of 1 mL·min~(-1). The column temperature was maintained at 30 ℃ and the detection wavelength was set at 250,280,310 and 340 nm. The technique of wavelength overlapping fingerprint was established and the contents of 7 indicative compounds have been determined in this method. The results of wavelength overlapping HPLC fingerprint showed all-around information of the fingerprints at 250,280,310 and 340 nm,and the similarity among 17 batches of Danshen was over 0. 828-0. 936. In wavelength overlapping HPLC fingerprint,15 common peaks were selected as the common peaks,and 7 contents of them were indentified as rosmarinic acid,salvianolic acid B,salvianolic acid A,phenolic acid,dihydrotanshinone Ⅰ,tanshinone Ⅰ and tanshinone ⅡA. The results of methodological study demonstrated that the method met the requirements of the determination. The method established in this study is simple,convenient and durable,which can provide a scientific basis for the quality control of Danshen.

The effect of sodium butyrate on T helper cell 17 and the signal pathway of toll-like receptors 4 in autoimmune hepatitis / 中华传染病杂志

Objective To study the immunoregulatory effect of sodium butyrate(NaB)on T helper cell 17(Th17)and the effect on toll-like receptor 4(TLR4)signal pathway in autoimmune hepatitis (AIH).Methods Fifty male C57BL/6 mice(6 weeks of age)according to the random number table method divided into control group(n=10),AIH group(n=10),NaB group(n=10)and high roughage diet(HRD)group(n=10),and the other ten mice were used to extract hepatic sytosolic S-100.After the establishment of AIH model,mice in NaB group were given sodium butyrate 500 mg/(kg·d)by gavage and those in HRD group were fed with high-fiber stuff.After 3 weeks of treatment,all the mice were sacrificed.The pathological change was observed.The serum levels of alanine aminotransferase(ALT), aspartate transaminase(AST),IL-17A and TNF-α,the proportion of Th17 in spleen,the expression levels of TLR4 and myeloid differentiation factor 88(MyD88)in liver were observed in each group.The tests of normality and homogeneity of variance were used to compare the means of each group.One-way analysis of variance and multiple comparative analyses were used in the statistical analysis.Results HE staining showed that inflammatory cell infiltration and hepatocyte necrosis were significantly reduced in mice treated with NaB and HRD compared to AIH group.Serum ALT levels in control group,AIH group,NaB group and HRD group were(24.833 ± 2.229),(88.333 ± 9.543),(27.167 ± 3.189)and (29.833 ± 6.113)U/L,respectively,while AST levels in each group were(97.00 ± 14.953),(285.000 ± 35.434),(139.500 ± 38.976)and(127.167 ± 28.687)U/L,respectively.The differences among groups were all statistically significant(F=156.49 and 44.118,respectively,both P<0.01).The proportion of Th17 in spleen and the expressions of the transcription factors retinoid-related orphan receptor gamma t in the spleen of the NaB group and HRD group were significantly lower than those of AIH group.The differences were statistically significantly(F=21.780 and 68.283,respectively,both P<0.05).The expressions of TLR4 and MyD88 in liver of AIH group were significantly higher than control group,but those were inhibited in NaB group and HRD group.The differences were statistically significantly(F= 26.235 and 28.293,respectively,both P<0.01).The expressions of IL-17 and TNF-α in liver and serum decreased in NaB group and HRD group.Conclusion NaB exerts an immunoregulatory effect in AIH and improves inflammatory reaction in liver.

Pharmaceutical inactivation of Erk1/2 does not affect function of FGF21 to regulate glucose and lipid metabolic hemostasis / 中国病理生理杂志

AIM: To investigate whether inactivation of extracellular signal-regulated kinase 1/2 ( Erk1/2 ) will affect the function of fibroblast growth factor 21 (FGF21) to regulate glucose and lipid metabolism .METHODS:Male db/db mice (8 weeks old) were treated with U0126 (an inhibitor of Erk1/2 kinase) for 1 week, and then treated with re-combinant human FGF21 protein and adenovirus-mediated FGF21 (Ad-FGF21).The profile changes of blood glucose and blood lipid were evaluated at 120 min or 4 weeks after FGF21 administration.Meanwhile, the molecular mechanism was ex-plored by in vitro study.RESULTS: Treatment of db/db mice with recombinant human FGF21 protein significantly re-duced blood glucose and triglyceride levels at 120 min after FGF21 administration , but these changes were comparable in U0126-treated mice .Furthermore , abnormal glucose and triglyceride levels , and glucose and insulin tolerance were strong-ly improved in db/db mice as accompanied with decreasing body fat content after 4 weeks of ad-FGF21 administration .In-terestingly, treatment with or without U0126 did not influence these effects of FGF21.Mechanically, treatment with Ad-FGF21 significantly upregulated the protein levels of p-Erk1/2 and peroxisome proliferator-activated receptor γ( PPARγ) as well as the expression of adiponectin at mRNA and protein levels in adipose tissues .However , treatment with or without U0126 did not change the profiles .On the other hand , in vitro experiments also indicated that treatment of adipocytes with recombinant human FGF 21 protein significantly activated Erk 1/2 phosphorylation , and upregulated the expression levels of PPARγand adiponectin (P<0.05).However, pre-administration of U0126 did not affect the profiles.CONCLUSION:Pharmaceutical inactivation of Erk 1/2 by U0216 does not affect the biological function of FGF 21 to regulate blood glucose balance and improve abnormal blood lipids in vivo.

Effect of adenosine A2A receptor agonist combined with bone marrow mesenchymal stem cells transplantation on the negative immune regulation in mice with acute liver failure / 中华传染病杂志

Objective To investigate the therapeutic effect and possible mechanism of adenosine A2A receptor agonist (CGS21680) combined with bone marrow mesenchymal stem cells (BMMSC) transplantation in acute liver failure (ALF).Methods Fifty male C57BL/6 mice, 6-8 weeks old, were fed with standard diet for 1 week and randomly divided into 5 groups according to random number table: healthy control group (n=6), model group (n=11), BMMSC group (n=11), CGS21680/BMMSC group (n=11) and CGS21680 group (n=11).Except healthy control group, the other mice were injected with D-GalN and lipopolysaccharide (LPS) to establish ALF model.Ten hours later, CGS21680/BMMSC group and CGS21680 group were injected intraperitoneally with adenosine A2A receptor agonist CGS21680 (2.1 mg/kg).In addition, the BMMSC group and CGS21680/BMMSC group were injected BMMSC (1×10.6) through tail vein.After 24 hours, pathological changes of liver tissue was observed by hematoxylin and eosin staining.The change of proportion of mouse splenic Treg among CD4+T lymphocytes was detected by flow cytometry.Toll-like receptor (TLR)4 and nuclear factor (NF)-κB expression levels in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction (PCR) and Western blot.One-way analysis of variance (one-way ANOVA) and SNK-q test was conducted for data analysis.Results Serum IL-6 levels were (23.67±2.97) pg/mL in healthy control group, (151.47±6.03) pg/mL in model control group, (72.10±3.74) pg/mL in BMMSC group, (53.35±2.50) pg/mL in CGS21680/BMMSC group and (84.85±3.25) pg/mL in CGS21680 group.The differences between healthy control group and the other 4 groups were all statistically significant (t=46.02, 25.51, 19.58 and 34.03, respectively, all P<0.01).Serum TNF-ɑ levels were (24.62±3.19) pg/mL in healthy control group, (102.25±2.10) pg/mL in model control group, (54.71±2.23) pg/mL in BMMSC group, (42.20±4.72) pg/mL in CGS21680/BMMSC group and (81.76±3.50) pg/mL in CGS21680 group.The differences between healthy control group and the other 4 groups were all statistically significant (t=46.49, 19.97, 7.72 and 29.57, respectively, all P<0.01).The differences of spleen Treg proportion in healthy control group were statistically significant compared with model control group, BMMSC group, CGS21680/BMMSC group and CGS21680 group (t=51.67, 12.22, 5.91 and 18.21, respectively, all P<0.01).The differences of TLR4 mRNA levels of liver tissue in healthy control group were statistically significant compared with model control group, BMMSC group, CGS21680/BMMSC group and CGS21680 group (t=26.31, 21.33, 13.24 and 27.14, respectively, all P<0.05).The differences of NF-κB mRNA level of liver tissue in healthy control group were statistically significant compared with model control group, BMMSC group, CGS21680/BMMSC group and CGS21680 group (t=16.56, 16.34, 7.83 and 13.11, respectively, all P<0.05).The differences of TLR4 protein level in liver tissue of healthy control group were statistically significant compared with model control group, BMMSC group, CGS21680/BMMSC group and CGS21680 group (t=35.60, 10.38, 6.05 and 18.02, respectively, all P<0.05).The differences of liver NF-κB protein level in the healthy control group were statistically significant compared with model control group, BMMSC group, CGS21680/BMMSC group and CGS21680 group (t=10.80, 7.30, 4.61 and 13.24, respectively, all P<0.05).Conclusions Adenosine A2A receptor agonist combined with BMMSC can significantly up-regulate the proportion of Treg cells in acute liver failure mice and inhibit the TLR4/NF-κB pathway activation, with both coordinated regulation, and further inhibit the liver inflammation.

Explore molecular mechanism of Chinese herbs with promoting blood circulation and resolving phlegm effects on myocardial ischemia reperfusion injury based on correlation between microRNA and mtDNA / 中国中药杂志

A large number of basic and clinical studies have shown that the Chinese herbs with promoting blood circulation and resolving phlegm effects could prevent and treat myocardial ischemia-reperfusion injury(MIRI) by regulating lipid metabolism. But its mechanism is not yet clear. The studies show that mitochondrial DNA (mtDNA), microRNAs and lipid metabolism participate in the whole process of MIRI and affect the prognosis. mtDNA mutation is the primary factor to cause myocardial ischemia and reperfusion myocardial cell damage. microRNAs aggravate or reduce MIRI injury by down-regulating or up-regulating related genes expression, while miR-33, as a key regulator of cholesterol transport, regulates lipid metabolism through CROT, PGC-1α, AMPK and other genes located in the mitochondria. There are less studies on correlation between miR-33 and mtDNA, microRNAs. Therefore, further studies on the correlation between miR-33 and mtDNA, microRNAs, as well as the discussions on whether the traditional Chinese medicine (TCM) with promoting blood circulation and resolving phlegm effects could target miR-33 to regulate lipid metabolism and inducemt DNA mutations or deletions, would have important significance for the prevention and treatment of MIRI.

Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Nurr1 plays an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons, and it is a potential target for Parkinson's disease (PD). Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs), but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.</p><p><b>METHODS</b>The mRNA levels of Nurr1 in PBMC of four subgroups of 362 PD patients and 193 healthy controls (HCs) using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurr1 expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level.</p><p><b>RESULTS</b>The relative Nurr1 mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments (de novo) (P < 0.001) and HC groups (P < 0.010), respectively. Furthermore, the increase in Nurr1 mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurr1 mRNA expression level in PBMC. In vitro, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurr1 mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively (P < 0.001).</p><p><b>CONCLUSIONS</b>DA agonists can induce Nurr1 expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.</p>

Role of zinc finger protein 1 in rat liver fibrosis and as related to TGFb expression / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To determine the role of zinc finger protein 1 (ZEB 1) in liver fibrosis and in regards to expression of the tumor growth factor-beta (TGFb) signaling factor using a rat model system.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into a normal (control) group, liver fibrosis (model) group and a liver fibrosis + therapy (ZEB1 intervention) group. The model group and the ZEB1 intervention group were given intraperitoneal injections of dimethylnitrosamine (DMN) for the first 3 days of each week over a 7-week period; starting at week 5, the ZEB 1 intervention group was started on a routine of every other day tail vein injections of recombinant ZEB1. During this 7-week period, the control group was given intraperitoneal injections of 0.9% NaC1 alone on the DMN schedule. Liver tissues were collected for pathological examination (with hematoxylin-eosin and Masson staining) and for detection of TGFb1 and ZEB 1 expression (by RT-PCR and western blotting). Measurement data were compared between groups using the single-factor analysis of variance test, followed by the least significant difference LSD test. Count data were analyzed by Fisher's exact test.</p><p><b>RESULTS</b>The model group's liver tissues showed degeneration and necrosis, as well as obvious fibrous septa accompanied by pseudo lobules. The ZEB 1 intervention group's liver tissues showed a significantly higher degree of fibrosis (x²=21.63, P=0), with more coarse fiber cords. The expression of ZEB1 and TGFb1 was significantly higher in the model group than in the control group (both P less than 0.05). However, the ZEB 1 intervention group showed the highest levels of ZEB 1 and TGFb1 expression (vs. model group, P less than 0.05).</p><p><b>CONCLUSION</b>ZEB 1 may promote the development of liver fibrosis in rats through a mechanism involving the TGFb/Smad signaling pathway.</p>

Effect of bone morphogenetic protein-7 intervention on epidermal growth factor receptor expression in liver fibrosis / 中华传染病杂志

Objective To investigate the dynamic expressions of epidermal growth factor receptor (EGFR) in mice with liver fibrosis and the effect of bone morphogenetic protein-7 (BMP-7) intervention on the expression of EGFR,and to explore a new therapy target for fibrosis.Methods A total of 30 healthy male ICR mice were randomly divided into three groups:6 mice in control group,18 mice in hepatic fibrosis group and 6 mice in BMP-7 intervention group.The model of mice with liver fibrosis was established by subcutaneous injection of carbon tetrachloride (CCl4) for 12 weeks.After administration of CCl4 for 8 weeks,human recombinant BMP-7 was given into mice in intervention group by intraperitoneal injection for 4 weeks.Hematoxylin-Eosin and Masson staining of liver tissues were employed to observe the pathological changes,and the semi-quantitative analysis of liver fibrosis was performed.Blood withdrawn from inferior vena cava was detected for levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and albumin (Alb).The expressions of transforming growth factor-β1 (TGF-β1)mRNA and TGF-β1,EGFR,phosphorylation EGFR (pEGFR) protein in each group were detected using quantitative real time polymerase chain reaction and Western blot.Measurement date was compared using analysis of variance and Pearson correlation analysis.Results The model of mice with liver fibrosis was successfully established.In model group,the serum levels of ALT and AST increased,while the level of Alb decreased gradually.All these biochemical index improved after intervention of BMP-7 (ALT:[153.9±18.1] U/L vs [191.3±24.5] U/L;AST:[177.8±19.2] U/L vs [206.6±25.0] U/L;Alb:[25.4±0.9] g/L vs [22.2±1.2] g/L; all P＜0.05).With the progress of fibrosis,TGF-β1,EGFR and pEGFR protein expressions increased gradually in model group and reached a peak at week 12,which was significantly different compared to the control group (all P＜0.05).In BMP-7 intervention group,the expressions of the three proteins decreased significantly compared to model group (TGF-β1:0.256 ± 0.006 vs 0.287±0.014,EGFR:1.061±0.017 vs 1.094±0.014,pEGFR:0.855±0.053 vs 1.007±0.063;all P＜0.05).Additionally,linear correlation analysis showed that expressions of both EGFR and pEGFR proteins were positively correlated with TGF-β1 protein (rs =0.895 and 0.859,respectively; both P＜0.05).Conclusions BMP-7 can suppress the pathogenesis of mouse liver fibrosis.The mechanism may rely on the regulation of EGFR and TGF-β1 expressions.

Expression of OX40 in the livers of endotoxin tolerance rats and its significance / 中华传染病杂志

Objective To investigate the mechanism of endotoxin tolerance (ETT) through observing the expression of OX40 in liver tissues of ETT rats.Methods SD male rats were randomly divided into three groups:normal group (n=6),acute liver failure (ALF) group (n=24) and ETT group (n=24).Lipopolysacharide (LPS) 0.1 mg/kg (ETT groups) or 0.9 ％NaC1 (ALF groups) was administered by five consecutive intraperitoneal injections at 24 h intervals,and at the sixth day,all animals were treated with intraperitoneal injections of D-galactosamine (D-GalN) 800 mg/kg and LPS 8 μg/rat.Blood and liver tissue were collected at 6,12,24 and 48 hours after the injection of D-GalN/LPS.The gene expression of OX40 in the liver was measured by reverse transcription-polymerase chain reaction (RT-PCR).The protein expression of OX40 was estimated by Western blot.The tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay (ELISA).The data analysis was performed by one-way ANOVA,lease significant difference (LSD) and Dunnett's T3 test.Results The expressions of TNF α and IL-6 were both significantly lower in ETT group compared to ALF group,but still higher than that of control group.The gene expressions of OX40 peaked at 12 hours and decreased gradually in ALF group.The gene expressions of OX40 were significantly lower in ETT group compared to ALF group (6 h:F=5.027,24 h:F=5.539,48 h:F=5.011,all P＜0.05; 12 h:F=36.688; P＜0.01),but still higher than that of normal group.The tendency of OX40 protein expression in ALF group was peaked at 12 hours and decreased at 24 hours.In ETT group,the expression of OX40 was lower,and the difference between ETT group and ALF group had statistical significance (6 h:F=8.658,P＜0.05; 12 h:F=34.611,24 h:F=28.176,48 h:F=16.747; all P＜0.01).Conclusions The level of OX40 is increased in ALF group,while the expressions of OX40,TNF-α and IL-6 are lower in ETT group,which suggested that OX40 may play an important role in the process of ETT.

The effect of endotoxin tolerance on the expression of chemokine receptor 7 in rats with the acute hepatic failure / 中华急诊医学杂志

Objective To study the effect of endotoxin tolerance (ETT) on chemokine receptor 7 (CXCR7) in the liver tissue of rats with acute liver failure (ALF).Methods SD male rats were randomly divided into three groups:normal group,ALF group and ETT group.The rats in the ETT group and ALF group were injected with lipopolysacharide (LPS) 0.1 mg/kg or saline respectively,one time / day for 5 days.At 24 hours after the 5th-day injection,all rats were injected with D-GalN 800 mg/kg and LPS 8μg/rat.Blood sample and liver tissue were collected on 2,6,12,24 and 48 hours after injection.The gene expressions of CXCR7 in the liver were measured by RT-PCR,and the protein expressions of CXCR7 were determined by Western Blot.The data analysis was performed by LSD,Dunnett's t test.Results The histological damage in the liver tissue was significantly mider in ETT group compared to ALF group.The gene expressions of CXCR7 were significantly milder in ETT group compared to ALF group (2 h:F =29.222,6 h:F=166.892,12 h:F=38.975,24h:F=34.603,48 h:F=18.929,allP＜0.01),but still severer than that of normal group.The CXCR7 protein expression in ALF group and ETT group peaked at 24 hours,but the expression of CXCR7 in ETT group was lower compared with that in in ALF group (2h:F=11.155,6 h:F=42.553,12h:F=17.082,all P＜0.01; 24 h:F=7.242,P＜0.05).Conclusions During the process of endotoxin tolerance,LPS pretreatment and D-GalN can decrease the liver injury,down-regulate the expressions of CXCR7mRNA and CXCR7.This suggests that CXCR7 may play an important role in the ETT.

Embryo development potential after intracytoplasmic injection of sperm from azoospermia patients with different spermatogenic functions / 中华男科学杂志

<p><b>OBJECTIVE</b>To analyze the embryo development potential after intracytoplasmic injection of sperm from azoospermia patients with different spermatogenic functions.</p><p><b>METHODS</b>We performed ICSI with sperm retrieved from azoospermia patients with different spermatogenic functions using percutaneous epididymal sperm aspiration (PESA) and testicular sperm aspiration (TESA). Then we recorded and analyzed the rates of normal fertilization, cleavages, excellent embryos and pregnancies.</p><p><b>RESULTS</b>No statistically significant differences were found between the PESA and TESA groups in the rates of normal fertilization ([74.9 +/- 19.6] vs [66.3 +/- 22.7]%, P > 0.05), cleavages ([96.7 +/- 8.6] vs [92.8 +/- 19.8]%, P > 0.05), excellent embryos ([43.5 +/- 26.2] vs [35.0 +/- 29.4]%, P > 0.05) and pregnancies (44.0 vs 52.0%, P > 0.05). The normal fertilization rates in the patients with normal spermatogenesis, mild spermatogenic dysfunction (SD), moderate SD and severe SD were (77.8 +/- 18.4), (68.4 +/- 18.5), (73.5 +/- 19.8) and (51.4 +/- 27.9)%, respectively, with significant difference between the normal spermatogenesis and mild SD groups (P < 0.05) as well as between the severe SD and the other groups (P < 0.05); the cleavage rates were (96.7 +/- 9.2), (96.5 +/- 15.0), (93.9 +/- 12.1) and (93.7 +/- 11.1)%, respectively, with no significant difference among the four groups; the excellent embryo rates were (47.1 +/- 25.8), (40.3 +/- 27.6), (36.2 +/- 23.1) and (15.0 +/- 24.6)%, respectively, with significant difference between the severe SD and the other groups; the pregnancy rates were 54.8, 50.0, 13.6 and 10.0%, respectively, with significant differences among the four groups (P < 0.001).</p><p><b>CONCLUSION</b>ICSI by PESA or TESA is an effective approach to azoospermia. There are no significant differences between PESA and TESA in the rates of normal fertilization, cleavages, excellent embryos and pregnancies. The severity of spermatogenic dysfunction affects fertilization and initial development of embryos, which were shown in the rates of normal fertilization, excellent embryos and pregnancies but not that of cleavages.</p>

Effects of bone morphogenetic protein-7 therapy on E3 ubiquitin ligase expression in mouse liver with experimentally induced fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>This study explored the dynamic expression of the E3 ubiquitin-protein ligase gene, Arkadia, in response to carbon tetrachloride (CCl4)-induced liver fibrosis in a mouse model and investigated the differential expression that occurs following treatment with the anti-fibrotic bone morphogenetic protein-7 (BMP-7).</p><p><b>METHODS</b>Thirty healthy male imprinting control region (ICR) mice were randomly assigned to three groups: normal (control; n = 6), CCl4-induced model group (model; n = 18), and CCl4-induced model with BMP-7 treatment group (treatment; n = 6). The model group was further divided into three subgroups (n = 6 each) for analysis at 4, 8 and 12 weeks after fibrosis induction. Liver fibrosis was induced by hypodermic injections of 60% CCl4 /peanut oil (5 mL/kg) to the hind legs of mice two-times per week in alternating legs for a period of 12 weeks. At week 9, the treatment group of CCl4-induced mice were given an intraperitoneal injection of BMP-7 (300 pg/g) simultaneously with that day's hypodermic injection of 60% CCl4 /peanut oil, and then every other day for a period of four weeks. The pathological changes in liver tissues were observed after staining with hematoxylin-eosin (HE) and Masson's trichrome. Messenger RNA (mRNA) and protein expression of Arkadia in liver were evaluated using reverse transcription-polymerase chain reaction and immunohistochemistry and Western blotting, respectively.</p><p><b>RESULTS</b>Mouse models of liver fibrosis were successfully established by CCl4 exposure. Arkadia, Smad7 and TGF-beta1 mRNA levels were up-regulated in the model group in a time-dependent manner (vs. control group), and BMP-7 treatment led to significant down-regulation of the CCl4-induced expression of the three genes (vs. control group: F = 812.80, 451.46, and 998.96, respectively; P less than 0.01). At week 12, the mRNA levels of Arkadia, Smad7, and TGF-b1 were significantly lower in the BMP-7 treatment group than in the model group (t = 12.108, 18.737, and 16.364, respectively; P less than 0.01). Arkadia, Smad7, and TGF-b1 protein staining was weak in the portal area of control liver tissue. In contrast, the model group showed significantly stronger staining for all three proteins in the portal area and in the cytoplasm of liver cells. The staining of Arkadia, Smad7, and TGF-b1 proteins was significantly lower in the treatment group (vs. control group: F = 8.399, 609.690, and 900.561, respectively; P < 0.01). At week 12, the protein levels of Arkadia, Smad7, and TGF-b1 were significantly lower in the treatment group than in the model group (t = 23.438, 11.667, and 42.889, respectively; P < 0.01).</p><p><b>CONCLUSION</b>Arkadia expression gradually increased along with the development of liver fibrosis but was suppressed by treatment with the anti-fibrotic factor, BMP-7.</p>

Association of serum uric acid levels with the progression of Parkinson's disease in Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Uric acid (UA) is suspected to play a neuro-protective role in Parkinson's disease (PD). This study aimed to evaluate whether the serum UA level was associated with the disease progression of PD in a relatively large population of Chinese patients.</p><p><b>METHODS</b>Serum UA levels were measured from 411 Chinese PD patients and 396 age-matched controls; following the uric acid colorimetric method, the serum creatinine (Scr) levels were also measured to reduce the bias caused by possible differences in renal excretion function. The disease progression was scored by Hoehn and Yahr (H&Y) scales and disease durations; PD group was divided into 3 subgroups according to H&Y scales. Independent-samples t test was performed to analyze the differences between PD group and control group. Multiple analysis of covariance was performed to analyze the differences between PD subgroups. Spearman rank-correlation was performed to evaluate the associations between serum UA or Scr level and disease progression.</p><p><b>RESULTS</b>PD patients were found to have significantly lower levels of serum UA than controls ((243.38 ± 78.91) vs. (282.97 ± 90.80) µmol/L, P < 0.01). As the disease progression, the serum UA levels were gradually reduced. There was a significantly inverse correlation of UA levels with H&Y scales (Rs = -0.429, P < 0.01) and disease duration (Rs = -0.284, P < 0.01) in PD patients of both females and males. No significant difference of the Scr level between PD patients and controls was found ((70.01 ± 14.70) vs. (69.84 ± 16.46) µmol/L), and the Scr level was not involved in disease progression.</p><p><b>CONCLUSION</b>Lower serum UA levels may possess a higher risk of PD, which may be a potential useful biomarker to indicate the progression of PD.</p>

A device for measuring the burning rate of light and thin homogeneous solid under low barometric pressure and in enriched oxygen / 生物医学工程学杂志

Oxygen enrichment of room air is an effective way to resist hypoxia at high altitude, but it may introduce a potential fire hazard. In common, the burning rate of light and thin homogeneous solid in oxygen enriched atmosphere was used to assess the fire hazard. For the purpose of measuring the burning rate of light and thin homogeneous solid in oxygen enriched atmosphere, we used the methods of laser contact ignition and direct calculation of burning rate, and invented a device that includes mixing gas system, ignition equipment, system of measuring the burning rate and self-made specimen frame. By using the homemade device, we studied the burning rate of filter paper under low pressure and in oxygen-enriched atmosphere and in that of the oxygen concentration of reached stationary burning rate. The results showed that this device was simple, and could obtain the burning rate of light and thin homogeneous solid quantitatively.

The inhibitory effect of bone morphogenetic protein 7 on proliferation of rat hepatic stellate cells / 中华传染病杂志

ObjectiveTo investigate the inhibitory effect of bone morphogenetic protein 7 (BMP7) on proliferation of rat hepatic stellate cells (HSC).MethodsHSC-T6 cells were cultured in vitro,and divided into four groups:control group,transforming growth factor (TGF) β1 group,TGFβ1 + BMP7 group,and TGFβ1 + BMP7 + Noggin group. The mRNA expressions of smad1,α-smooth muscle actin (α-SMA),gremlin and fibronectin (FN) were determined by semi-quantitative reverse transcriptasepolymerasechainreaction(RT-PCR).Theproteinexpressionsof phosphorylated-smad1/5/8 (P-smad1/5/8),α-SMA and gremlin were detected by Western blot.The statistical analysis were done using one-factor analysis of variance,LSD-t test,Dunnett's T3 test and Pearson linear correlation analysis.ResultsPhosphorylated-smad1/5/8,α-SMA,gremlin and FN were expressed on HSC-T6 cells in control group,which were significantly up-regulated after TGFβ1 stimulation (P＜0.05).The expressions of α-SMA,gremlin and FN were significantly down-regulated in TGFβ1 + BMP7 group compared with TGFβ1group, while P-smad1/5/8 expression was upregulated (1.613±0.031 vs.2.503±0.014; t=34.89,P＜0.05).The expressions of α-SMA,gremlin and FN in TGFβ1 + BMP7 + Noggin group were up-regulated than those in TGFβ1 + BMP7 group,while P-smad1/5/8 was down-regulated (t=34.05,P＜0.05).There was no difference of total smad1 mRNA expression among each group.ConclusionThese results collectively suggest that BMP7 strongly inhibits the expressions of α-SMA,gremlin and FN.