Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission ...Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.展开更多
Organofluorines play a crucial role in medicine,agrochemicals,and materials science.Adding fluorine to molecules creates structures with specific beneficial properties or tunes properties through interactions with the...Organofluorines play a crucial role in medicine,agrochemicals,and materials science.Adding fluorine to molecules creates structures with specific beneficial properties or tunes properties through interactions with their environment.Many popular pharmaceuticals and agrochemicals contain fluorine because it enhances hydrogen bonding at protein’s active sites.展开更多
Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predicto...Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.展开更多
Vitamins are natural materials essential for maintaining the normal physical function of the live cells. It has been reported that 13 vitamins are needed in our body, included vitamin A, B vitamins （thiamine, ribofla...Vitamins are natural materials essential for maintaining the normal physical function of the live cells. It has been reported that 13 vitamins are needed in our body, included vitamin A, B vitamins （thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid and cobalamin）, vitamin C, vitamin D, vitamin E and vitamin K. Nowadays, the functions of vitamins have been extensively investigated. The objective of this paper is to summarize the new functions of vitamins, aiming to provide suggestions on the usage of various vitamins in clinical application.展开更多
Using a modified C D function and stochastic frontier model, the paper analyzed China's cotton yield capacity and found that the yield and technical efficiency of China's cotton planting system can be increas...Using a modified C D function and stochastic frontier model, the paper analyzed China's cotton yield capacity and found that the yield and technical efficiency of China's cotton planting system can be increased by the use of genetically modified (GM) varieties.展开更多
Stroke is the leading cause of death and long-term disability worldwide,and cognitive impairment and dementia are major complications of ischemic stroke.Cystatin C (CysC) has been found to be a neuroprotective factor ...Stroke is the leading cause of death and long-term disability worldwide,and cognitive impairment and dementia are major complications of ischemic stroke.Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies.However,the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results.This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months.Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS).Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke.According to the MMSE score,308 patients (52.9%) had post-stroke cognitive dysfunction.After adjusting for potential confounding factors,the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30–0.98),compared with the lowest quartile.The correlation between serum CysC and cognitive dysfunction was modified by renal function status.We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044),but not in those with abnormal renal function.Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke,especially in those with normal renal function.The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction,and could be used to treat post-stroke cognitive dysfunction.The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No.2012-02) on December 30,2012,and was registered at ClinicalTrials.gov (identifier No.NCT01840072) on April 25,2013.展开更多
AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these res...AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels.METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated.RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids.Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test.CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.展开更多
This paper introduces the usage of these functions. It presents the technique of how to program with them to perform the serial communications between a computer and other digital devices by the serial porst in Window...This paper introduces the usage of these functions. It presents the technique of how to program with them to perform the serial communications between a computer and other digital devices by the serial porst in Windows95. The related sample codes of the applications of this technique written in C++ programming language are also given. This technique is applied successfully to receive the data of the radio noise from a frequency monitor.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32070989(to YMZ),31872766(to YMZ),81790640(to XLY),and 82070993(to SJW)the grant from Sanming Project of Medicine in Shenzhen,No.SZSM202011015(to XLY)。
文摘Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
文摘Organofluorines play a crucial role in medicine,agrochemicals,and materials science.Adding fluorine to molecules creates structures with specific beneficial properties or tunes properties through interactions with their environment.Many popular pharmaceuticals and agrochemicals contain fluorine because it enhances hydrogen bonding at protein’s active sites.
文摘Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.
文摘Vitamins are natural materials essential for maintaining the normal physical function of the live cells. It has been reported that 13 vitamins are needed in our body, included vitamin A, B vitamins （thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid and cobalamin）, vitamin C, vitamin D, vitamin E and vitamin K. Nowadays, the functions of vitamins have been extensively investigated. The objective of this paper is to summarize the new functions of vitamins, aiming to provide suggestions on the usage of various vitamins in clinical application.
文摘Using a modified C D function and stochastic frontier model, the paper analyzed China's cotton yield capacity and found that the yield and technical efficiency of China's cotton planting system can be increased by the use of genetically modified (GM) varieties.
基金supported by the National Natural Science Foundation of China,No.81673263(to YHZ)Ministry of Science and Technology of China,No.2016YFC1307300(to YHZ)a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions,China(to YHZ)
文摘Stroke is the leading cause of death and long-term disability worldwide,and cognitive impairment and dementia are major complications of ischemic stroke.Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies.However,the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results.This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months.Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS).Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke.According to the MMSE score,308 patients (52.9%) had post-stroke cognitive dysfunction.After adjusting for potential confounding factors,the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30–0.98),compared with the lowest quartile.The correlation between serum CysC and cognitive dysfunction was modified by renal function status.We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044),but not in those with abnormal renal function.Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke,especially in those with normal renal function.The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction,and could be used to treat post-stroke cognitive dysfunction.The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No.2012-02) on December 30,2012,and was registered at ClinicalTrials.gov (identifier No.NCT01840072) on April 25,2013.
文摘AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels.METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated.RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids.Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test.CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.
基金Supported by the 86 3 High Technology Project of China (86 3-818-0 1-0 2 )
文摘This paper introduces the usage of these functions. It presents the technique of how to program with them to perform the serial communications between a computer and other digital devices by the serial porst in Windows95. The related sample codes of the applications of this technique written in C++ programming language are also given. This technique is applied successfully to receive the data of the radio noise from a frequency monitor.
