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1.
Clin Rheumatol ; 41(3): 677-688, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34993729

ABSTRACT

OBJECTIVES: Janus kinase (JAK) inhibitors are a new class of medication for treatment of rheumatoid arthritis (RA), and such inhibitors alter levels of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in RA patients. However, the extent of such changes has not been systematically reviewed. METHOD: A systematic review and network meta-analysis was performed on randomized trials in RA patients in response to JAKi identified from Pubmed, Medline, Embase, and Cochrane Controlled Trials Register. The primary outcome was mean change of HDL-C and LDL-C from baseline. Mean treatment differences and the rank of the effect of various JAKi on HDL-C and LDL-C were estimated. RESULTS: Based on data from 18 unique studies involving five approved JAK inhibitors and 6697 RA patients (JAKi = 3341, placebo = 3356), such inhibitors led to a mean increase of 8.11 mg/dl (95% CI 6.65-9.58, I2 = 82%) in HDL levels from baseline, and a mean increase of 11.37 mg/dl (95% CI 7.84-14.91, I2 = 88%) in LDL levels from baseline. Cardiovascular disease risk did not differ significantly between patients who received JAK inhibitors or those who received placebo or active agents. CONCLUSIONS: Our analysis suggests that, at their recommended doses, all five JAK inhibitors lead to an increase in HDL and LDL levels in RA patients. Further long-term research is required to extend these results and understand whether changes in lipid levels in RA patients can affect cardiovascular risk. Key Points • This is the first systematic review and NMA examining the effect of all five clinically approved JAK inhibitors on lipid levels in RA patients. • Recommended doses of JAK inhibitors used for the treatment of RA patients can induce a significant increase in HDL and LDL levels. • Indirect pairwise comparisons suggest that only upadacitinib and peficitinib have significantly different ability to induce LDL change in RA patients.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Janus Kinase Inhibitors , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Heart Disease Risk Factors , Humans , Janus Kinase Inhibitors/adverse effects , Network Meta-Analysis
3.
Pharm Biol ; 59(1): 484-493, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33899689

ABSTRACT

CONTEXT: Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. OBJECTIVE: To observe the clinical safety and tolerability of CALAS. MATERIALS AND METHODS: Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. RESULTS: Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). DISCUSSION AND CONCLUSIONS: CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.


Subject(s)
Alkaloids/adverse effects , Alstonia/chemistry , Adult , Alkaloids/administration & dosage , Alkaloids/isolation & purification , Asian People , Cohort Studies , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Plant Leaves , Young Adult
4.
Article in English | MEDLINE | ID: mdl-33545501

ABSTRACT

BACKGROUND: This study aimed to develop a sensitive, accurate method for simultaneously quantifying cefuroxime and clindamycin in human serum, lumbar anulus fibrosus and nucleus pulposus. METHODS: Cefuroxime and clindamycin were quantified using ultra high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in multiple-reaction-monitoring mode on a triple-quadrupole AB Qtrap 5500 system in positive ion mode. Internal standards were D3-cefuroxime and D3,13C-clindamycin. Samples were pretreated by precipitating total protein. RESULTS: The method showed high sensitivity and good linearity over broad calibration ranges from 100 to 100 000 ng/mL for cefuroxime and 10 to 10 000 ng/mL for clindamycin in serum, and from 10 to 10 000 ng/mL for cefuroxime and 1 to 1 000 ng/mL for clindamycin in lumbar nucleus pulposus. In all sample types, correlation coefficients were greater than 0.99, intra- and inter-day precision (relative standard deviation) was less than 15%, and accuracy (relative error) was within 14% for both analytes. This method was effective at quantifying penetration of cefuroxime and clindamycin in patients undergoing oblique lumbar interbody fusion surgery. CONCLUSIONS: A very sensitive, specific method for simultaneous detection of cefuroxime and clindamycin has been developed for human lumbar anulus fibrosus, nucleus pulposus and serum samples.


Subject(s)
Annulus Fibrosus/chemistry , Cefuroxime/analysis , Chromatography, High Pressure Liquid/methods , Clindamycin/analysis , Nucleus Pulposus/chemistry , Annulus Fibrosus/metabolism , Cefuroxime/blood , Cefuroxime/pharmacokinetics , Clindamycin/blood , Clindamycin/pharmacokinetics , Humans , Linear Models , Lumbosacral Region , Nucleus Pulposus/metabolism , Reproducibility of Results , Sensitivity and Specificity , Tandem Mass Spectrometry/methods
5.
Nat Prod Bioprospect ; 11(1): 127-135, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33389714

ABSTRACT

Alstonia scholaris could be used as a traditional medicinal plant in China for the treatment of acute respiratory, which might be caused by respiratory tract infections. The investigation tested the anti-infective effects of total alkaloids extract (TA) from leaves of A. scholaris, and as a result, TA inhibited herpes simplex virus type 1 (HSV-1), respiratory syncytial virus (RSV) and influenza A virus (H1N1) in vitro respectively. In addition, the survival days of mice were prolonged, and the lung weights and mortality of mice were decreased significantly, after oral administrated TA in H1N1 and beta-hemolytic streptococcus infectious models in vivo respectively. The finding supported partly the traditional usage of A. scholaris in the treatment of respiratory infections.

6.
BMC Endocr Disord ; 20(1): 57, 2020 May 04.
Article in English | MEDLINE | ID: mdl-32366244

ABSTRACT

BACKGROUND: Lanreotide autogel is a somatostatin analog (SSA) approved for the treatment of acromegaly in 73 countries worldwide; however, it is not yet approved in China. The aim of this study was to evaluate the efficacy and safety of lanreotide autogel compared with lanreotide 40 mg prolonged release (PR) in Chinese patients with active acromegaly. METHODS: LANTERN was a phase 3, randomized, open-label, non-inferiority study. Patients with active acromegaly who had undergone surgery ≥3 months prior, or were unlikely or unable to undergo surgery, were treated with lanreotide autogel 60/90/120 mg (monthly deep subcutaneous injection) or lanreotide 40 mg PR (intramuscular injection every 7, 10, or 14 days) for 32 weeks. Primary endpoint was mean change-from-baseline in age-adjusted insulin-like growth factor-1 (IGF-1) standard deviation scores (SDS) at the end-of-study. Secondary endpoints included: growth hormone (GH) levels ≤2.5 µg/L or ≤ 1.0 µg/L, ≥20% reduction in tumor volume (TV) and safety. RESULTS: In total, 128 patients were randomized and received study treatment. Lanreotide autogel was non-inferior to lanreotide 40 mg PR: treatment difference (95% CI) for IGF-1 SDS between groups was - 0.32 (- 0.74, 0.11; per protocol population) and - 0.27 (- 0.63, 0.09; intention-to-treat [ITT] population), respectively. Reductions in IGF-1 (- 6.453 vs - 7.003) and GH levels (- 9.548 µg/L vs - 13.182 µg/L), and the proportion of patients with ≥1 acromegaly symptom (- 20.3% vs - 32.5%) were observed from baseline to end-of-study in lanreotide autogel and lanreotide 40 mg PR groups, respectively. In the lanreotide autogel group, 45.5% (25/55) patients achieved ≥20% reduction in TV compared with 50.9% (25/53) in lanreotide 40 mg PR group (ITT). Safety profiles were similar in both treatment groups. CONCLUSIONS: Lanreotide autogel was non-inferior to lanreotide 40 mg PR in Chinese patients with active acromegaly after 32 weeks of treatment. TRIAL REGISTRATION: Retrospectively registered on ClinicalTrials.gov: NCT02493517 (9 July 2015); prospectively registered on chinadrugtrials.org.cn: CTR20140698 (24 October 2014).


Subject(s)
Adenoma/drug therapy , Antineoplastic Agents/administration & dosage , Growth Hormone-Secreting Pituitary Adenoma/drug therapy , Peptides, Cyclic/administration & dosage , Somatostatin/analogs & derivatives , Adenoma/diagnostic imaging , Adenoma/metabolism , Adenoma/pathology , Adult , Antineoplastic Agents/therapeutic use , Blood Glucose/metabolism , China , Delayed-Action Preparations , Female , Glycated Hemoglobin/metabolism , Growth Hormone-Secreting Pituitary Adenoma/diagnostic imaging , Growth Hormone-Secreting Pituitary Adenoma/metabolism , Growth Hormone-Secreting Pituitary Adenoma/pathology , Human Growth Hormone/metabolism , Humans , Injections, Intramuscular , Injections, Subcutaneous , Insulin-Like Growth Factor I/metabolism , Magnetic Resonance Imaging , Male , Middle Aged , Peptides, Cyclic/therapeutic use , Somatostatin/administration & dosage , Somatostatin/therapeutic use , Treatment Outcome , Tumor Burden
7.
BMC Complement Altern Med ; 19(1): 336, 2019 Nov 27.
Article in English | MEDLINE | ID: mdl-31775729

ABSTRACT

BACKGROUND: This study aims to assess the tolerability and safety of DQTM tablet, which contains a complex mixture of Salvia miltiorrhiza salvianolic acids and Panax notoginseng saponins. METHODS: A double-blind, randomized, placebo-controlled phase I dose escalation study was conducted in 84 healthy volunteers. In a single ascending dose study, active ingredients were administered in various doses (90, 270, 540, 1080, 1800, 2880, 4320 or 5760 mg) to 60 subjects in cohorts 1-8. In a multiple ascending dose study, active ingredients were administered at doses of 360, 720 or 2160 mg twice daily to 24 subjects in cohorts 9-11 for 14 consecutive days. Safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiography, laboratory tests and adverse events. RESULTS: No serious adverse events or clinically significant changes in vital signs or electrocardiography were observed. One subject experienced mildly elevated levels of alanine aminotransferase and aspartate transaminase but recovered spontaneously. Five subjects experienced a small increase in the number of daily stools. CONCLUSIONS: DQTM tablet was well tolerated at single doses of up to 5760 mg and twice-daily doses of up to 2160 mg for 14 consecutive days. The most frequent adverse event was an increase in the number of daily stools.


Subject(s)
Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Adolescent , Adult , Double-Blind Method , Electrocardiography , Female , Healthy Volunteers , Humans , Male , Middle Aged , Tablets , Young Adult
8.
Eur J Pharm Sci ; 136: 104950, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-31173870

ABSTRACT

BACKGROUND: Yogliptin is a novel xanthine dipeptidyl peptidase-4 (DPP-4) inhibitor targeting type 2 diabetes. After promising preclinical pharmacological studies, the first human trial of yogliptin was designed. METHODS: A randomized, double-blind, parallel, placebo-controlled phase I single-dose escalation study was designed to evaluate the pharmacokinetics, pharmacodynamics, and tolerability after single oral doses of yogliptin in healthy Chinese subjects. Healthy subjects were assigned to nine cohorts, which received a single dose of yogliptin at 2.5, 5, 10, 25, 50, 100, 200, 400, or 600 mg. Two subjects in each cohort received placebo. Blood samples were collected before dosing and up to 192 h afterwards. Urine samples were collected until 120 h after dosing. Plasma and urine drug concentrations were determined using liquid chromatography coupled with tandem mass spectrometry, and DPP-4 activity was measured using a semi-quantitative, fluorescence-based kinetic assay. RESULTS: A total of 104 subjects were enrolled, 103 of whom completed the study (mean age, 25.3 years; mean weight, 58.8 kg; mean BMI, 21.8 kg/m2). A total of 27 adverse events (AEs) occurred in 25 of 86 yogliptin subjects (29.1%), and 3 AEs occurred in 3 of 18 placebo subjects (16.7%). Yogliptin was absorbed with a median time of maximum observed concentration (Tmax) of 3.0 h and was eliminated slowly with a t1/2 of 25.45-43.84 h. The maximum observed concentration (Cmax) and area under the curve (AUC) varied slightly more than dose-proportionally over the dose range from 2.5 to 400 mg. The fraction of drug excreted in urine ranged from 8.39% to 24.77%. Mean DPP-4 inhibition at 24 h after dosing ranged from 97.7% to 99.5%, and DPP-4 inhibition was >80% for 72 h at doses from 25 to 400 mg. DPP-4 inhibition was >80% for 1 week in the group receiving 400 mg. CONCLUSION: Yogliptin was well tolerated in healthy subjects, with no dose-limiting toxicity observed in the range from 2.5 to 600 mg. Yogliptin inhibited plasma DPP-4 activity for 72 h at single doses of 25-200 mg and for 1 week at 400 mg, suggesting that once-weekly dosing of yogliptin is possible in type 2 diabetes patients. TRIAL REGISTRATION: ChiCTR-IIR-17010311 (Chictr.org).


Subject(s)
Dipeptidyl-Peptidase IV Inhibitors/pharmacokinetics , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Adolescent , Adult , Area Under Curve , Asian People , Blood Glucose/drug effects , Cohort Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Dipeptidyl Peptidase 4/metabolism , Dose-Response Relationship, Drug , Double-Blind Method , Female , Healthy Volunteers , Humans , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/therapeutic use , Male
9.
Phytomedicine ; 61: 152828, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31055046

ABSTRACT

BACKGROUND: Alstonia scholaris (Apocynaceae) was reported to be a rich source of indole alkaloids, which exhibited remarkably bioactivities. The leaf of A. scholaris has been used in 'dai' ethno-medicine for treatment of respiratory diseases, and the defined indole alkaloids from leaf of A. scholaris has been registered as investigational new botanical drug (No. 2011L01436) and was approved for phase I/II clinical trials by China Food and Drug Administration (CFDA). PURPOSE: The aim of the trial is to evaluate the safety and explore the relationship of dosing frequency and pharmacokinetics after oral administration of capsule of alkaloids from leaf of A. scholaris (CALAS) at different doses. METHODS: In this randomized, open-labelled, single-center clinical trial, the safety and pharmacokinetics of CALAS were assessed in eligible healthy Chinese volunteers after oral administration of different doses. Each volunteer (n = 10 per group) received single dose of CALAS from 20 mg, 40 mg, 80 mg to 120 mg orally. The pharmacokinetics of CALAS was investigated in healthy Chinese subjects' plasma by a fully-validated LC-MS/MS method. Safety was assessed biochemically and clinically throughout the study, and drug re-excitation research was conducted to verify the correlation between investigational product and minor adverse events. The trial was registered on August 26, 2015 (http://www.chictr.org.cn/showproj.aspx?proj=11736), number ChiCTR-IPR-15006976. RESULTS: 40 subjects completed the study, and as a result, vallesamine had the highest concentration in plasma of healthy volunteers, and the AUC exposure level in each compounds in turn is vallesamine > scholaricine > 19-epischolaricine > picrinine. For the safety evaluation of CALAS, two cases of minor adverse events were observed during the trial, but the drug re-excitation research indicated that these two adverse events were related to the individual's physiological variation. CONCLUSION: Pharmacokinetic characteristics of each ingredient showed different patterns. 19-epischolaricine, vallesamine and picrinine were match to the linear pharmacokinetic characteristics, but scholaricine conformed to the characteristics of nonlinear pharmacokinetics. The CALAS was safe in healthy subjects under the current dose regimen.


Subject(s)
Alkaloids/administration & dosage , Alkaloids/pharmacokinetics , Alstonia/chemistry , Administration, Oral , Adult , Alkaloids/adverse effects , Alkaloids/blood , Area Under Curve , Asian People , Chromatography, Liquid , Female , Healthy Volunteers , Humans , Indole Alkaloids/blood , Male , Plant Leaves/chemistry , Reproducibility of Results , Tandem Mass Spectrometry
10.
Eur J Pharm Sci ; 130: 166-172, 2019 Mar 15.
Article in English | MEDLINE | ID: mdl-30703444

ABSTRACT

BACKGROUND: Moguisteine is a non-narcotic peripheral antitussive drug that has been effective and well-tolerated in clinical studies. The aim of the present work was to investigate the pharmacokinetics of moguisteine given as single or multiple doses to healthy Chinese subjects. METHODS: In Stages 1-3 of this study, 12 healthy Chinese subjects (6 males and 6 females) participated in a randomized, open-label, single-dose, 3-period, 3-way crossover study, with a 24-h washout period between each treatment. Eligible subjects were randomized to receive a single dose of 100, 200 or 400 mg moguisteine. Blood was sampled before and up to 10 h after administration. In those receiving 200 mg moguisteine, urine was sampled at intervals of 0-2, 2-4, 4-6, 6-10, and 10-24 h. In Stage 4, subjects received a moguisteine tablet containing 200 mg three times daily for five consecutive days. Blood was sampled for up to 10 h after the last dose. HPLC-tandem mass spectrometry was used to determine concentrations of the moguisteine metabolite M1 in serum, while HPLC-UV was used to determine concentrations of M1 in urine. Safety of the dosing schedules was assessed based on physical examination, recording of adverse events, 12-lead electrocardiography, and laboratory tests. RESULTS: All subjects completed all four stages of the study. M1 was detectable at the shortest time points after moguisteine administration; the time to achieve peak concentration was 0.5-1.0 h in single dosing and 1.5 h in multiple dosing. Elimination half-life (t1/2) was 0.91-1.54 h in single dosing and 1.57 h in multiple dosing. AUC increased roughly proportionally with dose, while Cmax increased much more gradually with dose. During 5-day dosing of three tablets per day, a steady state concentration was reached on day 3, and the mean accumulation ratio was 0.87. At 24 h after a single dose of 200 mg moguisteine, approximately 34.0% of the resulting M1 was recovered in urine. Pharmacokinetics of moguisteine did not differ significantly between men and women, except among those receiving a single dose of 100 mg (P < 0.05). Mild adverse events (nausea, loose stool, abdominal distention, or dizziness) occurred in six subjects and resolved without treatment, while no serious adverse events were observed. CONCLUSION: Moguisteine was safe and well-tolerated by our healthy subjects, and it exhibited dose linearity but not proportionality when a single dose of 100-400 mg was given. M1 did not accumulate in subjects after multiple doses of moguisteine.


Subject(s)
Antitussive Agents/administration & dosage , Antitussive Agents/pharmacokinetics , Asian People , Thiazolidines/administration & dosage , Thiazolidines/pharmacokinetics , Adolescent , Adult , Asian People/genetics , Cross-Over Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Healthy Volunteers , Humans , Male , Middle Aged , Young Adult
11.
Int J Med Inform ; 108: 13-21, 2017 12.
Article in English | MEDLINE | ID: mdl-29132618

ABSTRACT

BACKGROUND: Telehealth aims to revolutionize health care by migrating health care from hospitals and satellite clinics directly into the home and onto mobile devices. Telehealth has the potential to increase public access to healthcare in China, where large segments of the population remain underserved, yet little is known about current attitudes and use of telehealth in the country. OBJECTIVE: Our aim was to determine attitudes and use of telehealth in China among medical professionals and patients, as well as identify factors that may affect its use. METHODS: Using a custom-designed questionnaire, we performed a cross-sectional survey of medical professionals, medical students and patients at three large hospitals in Chengdu, Sichuan, China. We used a structural model to analyze the influence of factors that may affect use of telehealth. RESULTS: Of 600 questionnaires that were distributed, 550 (96.49%) were analyzed. Most respondents (63.28%) were familiar with using telehealth to "schedule medical appointments/pay medical fees online", but relatively few (28.55%) used this feature. Nearly half of respondents were familiar with the concept of a "virtual visit" (46.18%), but only 12.18% had ever engaged in such visits. Medical professionals and students generally showed higher awareness and greater use of telehealth than patients. The strongest concern about telehealth among respondents was "authenticity and reliability of data from remote monitoring of patients" (75.17%). The proportion of respondents concerned about the potential disadvantages of telehealth was highest among students and lowest among patients. Awareness and use of telehealth were associated with previous experience with health-related use of the Internet and experience with traditional forms of telehealth, but not with social status or attitude toward telehealth. CONCLUSIONS: Medical professionals and patients alike in China have a high awareness of telehealth, primarily traditional forms of telehealth, but only a small percentage actually use it. Patients have much lower awareness and use of telehealth than medical professionals and medical students, though they have generally positive attitudes towards telehealth. Telehealth is still in its infancy in China, and the environment for its development is largely favorable among current and future medical professionals.


Subject(s)
Attitude of Health Personnel , Attitude to Health , Internet/statistics & numerical data , Patients/psychology , Students, Medical/psychology , Telemedicine/methods , Telemedicine/statistics & numerical data , Adolescent , Adult , Aged , Child , China , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Reproducibility of Results , Surveys and Questionnaires , Young Adult
12.
Asian J Androl ; 19(5): 586-590, 2017.
Article in English | MEDLINE | ID: mdl-27586028

ABSTRACT

The aim of this study is to evaluate the ability of the random forest algorithm that combines data on transrectal ultrasound findings, age, and serum levels of prostate-specific antigen to predict prostate carcinoma. Clinico-demographic data were analyzed for 941 patients with prostate diseases treated at our hospital, including age, serum prostate-specific antigen levels, transrectal ultrasound findings, and pathology diagnosis based on ultrasound-guided needle biopsy of the prostate. These data were compared between patients with and without prostate cancer using the Chi-square test, and then entered into the random forest model to predict diagnosis. Patients with and without prostate cancer differed significantly in age and serum prostate-specific antigen levels (P < 0.001), as well as in all transrectal ultrasound characteristics (P < 0.05) except uneven echo (P = 0.609). The random forest model based on age, prostate-specific antigen and ultrasound predicted prostate cancer with an accuracy of 83.10%, sensitivity of 65.64%, and specificity of 93.83%. Positive predictive value was 86.72%, and negative predictive value was 81.64%. By integrating age, prostate-specific antigen levels and transrectal ultrasound findings, the random forest algorithm shows better diagnostic performance for prostate cancer than either diagnostic indicator on its own. This algorithm may help improve diagnosis of the disease by identifying patients at high risk for biopsy.


Subject(s)
Algorithms , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Aging , Biopsy , Humans , Image-Guided Biopsy , Male , Middle Aged , Predictive Value of Tests , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Rectum/diagnostic imaging , Sensitivity and Specificity , Ultrasonography , Young Adult
13.
Nephrol Dial Transplant ; 32(6): 1032-1040, 2017 Jun 01.
Article in English | MEDLINE | ID: mdl-27190348

ABSTRACT

BACKGROUND: Residual renal function needs to be assessed frequently in patients on continuous ambulatory peritoneal dialysis (CAPD). A commonly used method is to measure creatinine (Cr) and urea clearance in urine collected over 24 h, but collection can be cumbersome and difficult to manage. A faster, simpler alternative is to measure levels of cystatin C (CysC) in serum, but the accuracy and reliability of this method is controversial. Our study aims to validate published CysC-based equations for estimating residual renal function in patients on CAPD. METHODS: Residual renal function was measured by calculating average clearance of urea and Cr in 24-h urine as well as by applying CysC- or Cr-based equations published by Hoek and Yang. We then compared the performance of the equations against the 24-h urine results. RESULTS: In our sample of 255 patients ages 47.9 ± 15.6 years, the serum CysC level was 6.43 ± 1.13 mg/L. Serum CysC level was not significantly associated with age, gender, height, weight, body mass index, hemoglobin, intact parathyroid hormone, normalized protein catabolic rate or the presence of diabetes. In contrast, serum CysC levels did correlate with peritoneal clearance of CysC and with levels of prealbumin and high-sensitivity C-reactive protein. Residual renal function was 2.56 ± 2.07 mL/min/1.73 m 2 based on 24-h urine sampling, compared with estimates (mL/min/1.73 m 2 ) of 2.98 ± 0.66 for Hoek's equation, 2.03 ± 0.97 for Yang's CysC-based equation and 2.70 ± 1.30 for Yang's Cr-based equation. Accuracies within 30%/50% of measured residual renal function for the three equations were 29.02/48.24, 34.90/56.86 and 31.37/54.90. CONCLUSION: The three equations for estimating residual renal function showed similar limits of agreement and differed significantly from the measured value. Published CysC-based equations do not appear to be particularly reliable for patients on CAPD. Further development and validation of CysC-based equations should take into account peritoneal clearance of CysC and other relevant factors.


Subject(s)
Cystatin C/blood , Glomerulonephritis/blood , Peritoneal Dialysis, Continuous Ambulatory , Adult , Algorithms , Biomarkers/blood , C-Reactive Protein/metabolism , Creatinine/blood , Female , Glomerular Filtration Rate , Glomerulonephritis/diagnosis , Glomerulonephritis/physiopathology , Glomerulonephritis/therapy , Humans , Male , Middle Aged , Reproducibility of Results , Urea/blood
14.
Zhonghua Nan Ke Xue ; 22(6): 506-510, 2016 Jun.
Article in Chinese | MEDLINE | ID: mdl-28963838

ABSTRACT

OBJECTIVE: To evaluate the integrated performance of age, serum PSA, and transrectal ultrasound images in the prediction of prostate cancer using a Tree-Augmented NaÏve (TAN) Bayesian network model. METHODS: We collected such data as age, serum PSA, transrectal ultrasound findings, and pathological diagnoses from 941 male patients who underwent prostate biopsy from January 2008 to September 2011. Using a TAN Bayesian network model, we analyzed the data for predicting prostate cancer, and compared them with the gold standards of pathological diagnosis. RESULTS: The accuracy, sensitivity, specificity, positive prediction rate, and negative prediction rate of the TAN Bayesian network model were 85.11%, 88.37%, 83.67%, 70.37%, and 94.25%, respectively. CONCLUSIONS: Based on age, serum PSA, and transrectal ultrasound images, the TAN Bayesian network model has a high value for the prediction of prostate cancer, and can help improve the clinical screening and diagnosis of the disease.


Subject(s)
Bayes Theorem , Prostatic Neoplasms/diagnosis , Biopsy , Humans , Male , Predictive Value of Tests , Prostate , Prostate-Specific Antigen/blood , Sensitivity and Specificity
15.
Hum Gene Ther ; 26(12): 841-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26414282

ABSTRACT

Gene therapy is becoming an important treatment modality for gravely ill patients, and today's medical students and postgraduates are both potential consumers and future providers of gene therapy. Therefore, their attitudes and concerns about gene therapy may directly influence its long-term development and implementation in the clinic. We performed a cross-sectional survey of medical students and postgraduates at West China Medical School of Sichuan University. A custom-designed questionnaire was distributed to 600 students, and 579 were valid (96.98% response). Most respondents (84.46%) indicated little prior knowledge about gene therapy. The proportion of respondents considering gene therapy as acceptable ranged from 63.73% for serious illness to 17.72% for genetic enhancement. Adverse side effects were the most frequent concern among respondents when asked to imagine that they would receive gene therapy to treat a severe brain-related illness. These results suggest that medical students in China consider gene therapy's acceptability to be rather low, and are most concerned about its adverse side effects.


Subject(s)
Attitude of Health Personnel , Genetic Therapy/ethics , Students, Medical/psychology , Adolescent , Adult , China , Cross-Sectional Studies , Education, Medical, Graduate , Female , Humans , Male , Surveys and Questionnaires
16.
Diabetes Res Clin Pract ; 109(2): 334-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26044612

ABSTRACT

AIMS: Sulfonylurea drugs exert an insulinotropic effect through ATP-sensitive potassium (KATP) channel inhibition in pancreatic islet cells. These channels are also expressed in cardiomyocytes and vascular smooth muscle cells (VSMCs), suggesting potential for adverse cardiovascular effects. We evaluated the effects of Gliquidone (Glq) on sulfonylurea receptors in HIT-T15 cells (SUR1), cardiomyocytes (SUR2A), and VSMCs (SUR2B). METHODS: The concentration-dependent effects of Glq (0.001-500 µM) on KATP channels were assessed using whole-cell patch clamp in HIT-T15 cells, rat cardiomyocytes, and VSMCs. Parallel studies using Glibenclamide (Glb) (0.001-10 µM) and Gliclazide (Glc) (0.01-500 µM)were conducted as controls. RESULTS: In HIT-T15 cells, Glb exhibited the lowest IC50 (0.03 µM), as compared to Glq (0.45µM) and Glc (1.21µM). However, Glq had higher IC50 in cardiomyoctes and VSMCs, as compared to Glb (119.1 vs. 0.01 and 149.7 vs. 0.09 µM, respectively), suggesting that Glq is more selective to ß-cells than Glb. Thus, Glq may have fewer side effects in cardiomyoctes and VSMCs. CONCLUSIONS: Glq is a highly selective SUR secretagogue with moderate affinity to ß-cells, but low affinity to cardiomyocytes and VSMCs. Our data also reveal the non-selective nature of Glb, as evidenced by high binding affinity to KATP channels in all the three cell types examined.


Subject(s)
Insulin-Secreting Cells/metabolism , KATP Channels/metabolism , Muscle, Smooth, Vascular/drug effects , Myocytes, Cardiac/metabolism , Sulfonylurea Compounds/pharmacology , Animals , Cell Line , Cricetinae , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/drug effects , KATP Channels/drug effects , Male , Muscle, Smooth, Vascular/metabolism , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Rats , Rats, Sprague-Dawley , Sulfonylurea Receptors
17.
Phytother Res ; 28(1): 132-6, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23519822

ABSTRACT

This study aims to assess the efficacy and safety of Rehmannia glutinosa acteosides used in combination with the angiotensin receptor blocker irbesartan to treat primary chronic glomerulonephritis. A total of 479 patients diagnosed with primary chronic glomerulonephritis were recruited from outpatient clinics and were randomly assigned to the treatment group (Rehmannia glutinosa acteosides, two 200-mg capsules, bid; and irbesartan, one 150-mg tablet, qd) or the control group (irbesartan, one 150-mg tablet, qd). The primary outcome was 24-h urinary protein. Secondary outcome measures included blood pressure, estimated glomerular filtration rate, erythrocyturia, serum alanine aminotransferase, aspartate transaminase and electrolytes. After 8 weeks of treatment, the treatment group showed a mean reduction in 24-h proteinuria of 36.42% compared to baseline, which was significantly higher than the mean reduction from baseline of 27.97% in the control group (P = 0.0278).Adverse drug reactions occurred at a similarly low rate in the treatment group (0.4%) and control group (1.2%, P = 0.3724). In the treatment of chronic glomerulonephritis, the combination of Rehmannia glutinosa acteosides and irbesartan can reduce proteinuria more effectively than irbesartan alone.


Subject(s)
Biphenyl Compounds/therapeutic use , Glomerulonephritis/drug therapy , Glucosides/therapeutic use , Phenols/therapeutic use , Rehmannia/chemistry , Tetrazoles/therapeutic use , Adult , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Blood Pressure/drug effects , Female , Humans , Irbesartan , Male , Middle Aged , Proteinuria/drug therapy
18.
Chin Med J (Engl) ; 126(5): 803-7, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23489780

ABSTRACT

BACKGROUND: Alcohol has been used for treating simple renal cysts since 1981. Since then, various observational studies have examined the technique, but they differ significantly in the details of the procedures and efficacy measures used. This has made it difficult to assess the safety and efficacy of this technique. We carried out a randomized controlled trial to evaluate the efficacy and safety of ultrasound-guided alcohol sclerotherapy involving single-session multiple injections to treat simple renal cysts. METHODS: A total of 144 patients with simple renal cysts were randomly allocated to either the treatment group (ultrasound-guided percutaneous drainage and alcohol sclerotherapy with single-session multiple injections) or control group (ultrasound-guided simple percutaneous drainage). Follow-up CT scans of ablated cysts were collected 3 and 6 months after the procedure. The outcome was considered successful if cyst volume between baseline and 6 months decreased by at least 87.5%. RESULTS: Intention-to-treat analysis revealed an average volume reduction of 94.2% in the treatment group and 50.8% in the control group (P < 0.0001). The percentage of patients achieving successful outcomes was 88.9% (95%CI 77.0% - 100.0%) in the treatment group and 22.2% (95%CI 6.54% - 37.9%) in the control group (P < 0.0001). The corresponding results in the per-protocol analysis were an average volume reduction of 96.4% in the treatment group and 50.8% in the control group (P < 0.0001). The percentage of patients achieving a successful outcome was 94.3% (95%CI 85.6% - 100.0%) in the treatment group and 22.2% (95%CI 6.54% - 37.9%) in the control group (P < 0.0001). CONCLUSION: Alcohol sclerotherapy involving single-session multiple injections is safe and efficacious in the treatment of renal cysts.


Subject(s)
Kidney Diseases, Cystic/therapy , Sclerosing Solutions/therapeutic use , Sclerotherapy/methods , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Treatment Outcome , Young Adult
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