Clinical value of captopril test in noninvasive diagnosis of aldosterone-producing adenoma / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical characteristics of aldosterone-producing adenoma (APA) subtypes in primary aldosteronism (PA) and the application value of captopril challenge test (CCT) in adenomas. And to find out the clinically specific non-invasive index for identifying APA subtypes from PA.@*METHODS@#The clinical data of hospitalized patients with hypertension were retrospectively collected. All the patients were conducted with the CCT and 90 patients with PA were confirmed. Among them, 34 patients were confirmed to have APA by surgery. The clinical indicators of the two groups of patients including plasma aldosterone concentration (PAC), aldosterone inhibition rate (%), and aldosterone to renin ratio (ARR) before and after the CCT were compared, the receiver operating characteristic (ROC) curves for the relevant indicators before and after the CCT drawn, and the areas under the curve (AUC) compared. The ROC curves were used to analyze the efficiency of the different CCT diagnostic criteria for diagnosing APA.@*RESULTS@#Compared with the PA group, the duration of hypertension was shorter, the incidence of hypokalemia was higher, and the average serum potassium level was lower when APA was diagnosed. There were no significant differences in blood pressure level, gender, serum sodium and body mass index between the two groups. Compared with PA population, APA group had higher PAC and ARR whether before or after the CCT, but lower plasma renin concentration (PRC). In APA patients, the mean degree of PAC declined after CCT was approximately 5.7%, but 5% with that of PA. As for diagnosing, ARR before or after CCT had diagnostic value for APA, in which the ARR cut-off point was 7.12, which yielded a sensitivity and specificity of 35.85% and 77.78%. The cut-off point of ARR after CCT was 4.23, with a sensitivity of 71.43% and specificity of 62.22%. For the diagnosis, the ARR before and after CCT were of no significant difference. However, the diagnostic specificity of ARR>7.12 combined with hypokalemia was up to 80%.@*CONCLUSION@#ARR before or after CCT have clinical value for the diagnosis of APA from PA, when combined with hypokalemia yielded high specificity.

β-adrenergic receptor activation promotes cardiac miR-21 expression by paracrine action of IL-6 from fibroblasts / 中国病理生理杂志

AIM:To investigate the regulation ofβ-adrenergic receptor (β-AR) agonist isoproterenol (ISO) on cardiac microRNA-21 (miR-21) expression.METHODS:The primary cultured mouse cardiomyocytes and cardiac fibroblasts were isolated by enzyme digestion and treated with ISO at 10μmol/L for 1, 6, 12, 24 and 48 h.The expression of miR-21 was detected by real-time PCR.The protein levels of p-STAT3 and STAT3 were determined by Western blot, and the concentration of interleukin-6 (IL-6) in the cultured supernatant was measured by ELISA.The cells were transfected with the luciferase reporter gene plasmid p GL3-21PPR containing the miR-21 promoter region, and the luciferase reporter gene assay was used to examine the effect of conditioned medium on the transcriptional activity of miR-21.RESULTS:The medium supernatant produced by ISO on cardiac fibroblasts was used as the conditioned medium, which increased the miR-21 expression in the cardiomyocytes in a time-dependent manner after fibroblasts was treated with ISO (P<0.05).The conditioned medium caused a significant increase in the transcriptional activity of miR-21 in the cardiomyocytes, while24 h and 48 h conditioned medium increased the transcriptional activity by 94.9％and 77.1％, respectively (P<0.01).The concentration of IL-6 in the conditioned medium was significantly increased, and the activity of transcriptional factor STAT3 was enhanced by paracrine action of IL-6 in the cardiomyocytes, which promoted the transcription and expression of miR-21.CONCLUSION:β-AR stimulation induces fibroblast synthesis and expression of IL-6 with paracrine effect on cardiomyocytes, up-regulates the expression of miR-21 in cardiomyocytes by IL-6/STAT3 pathway, and participates in the cardiac remodeling.

Active ingredients screening by cell membrane chromatography and simultaneous quantitation of ginsenosides in bulk drug of secondary ginsenoside H dripping pills / 中草药

To establish a HPLC-MS/MS method for simultaneous determination and active ingredients screening of pseudoginsenoside RT5, 20(S)-ginsenoside Rh1 and 20(S)-ginsenoside Rh2 by cell membrane chromatography (CMC) in secondary ginsenoside H dripping pills (SGHDP). Methods The samples were separated on Century SIL BDS C18 column (250 mm × 4.6 mm, 5 μm) eluted with 0.2% formic acid aqueous solution-acetonitrile in a gradient mode, and the target compounds were analyzed by positive ion multiple reaction monitoring (MRM) mode, and active ingredients of SGHDP obtained in solid-phase of biomembrane by CMC technology were determined at the same time. Results The linear ranges of pseudoginsenoside RT5, 20(S)-ginsenoside Rh1, and 20(S)-ginsenoside Rh2 were 0.095-0.235, 0.042-0.168, and 0.105-0.419 mg/mL; the extraction recoveries were 99.95%, 100.12%, and 100.06%; and RSD were 1.06%, 0.96%, and 0.91%, respectively. The contents of pseudoginsenoside RT5, 20(S)-ginsenoside Rh1, and 20(S)-ginsenoside Rh2 in SGHDP were 21.24%, 21.42%, and 29.70%, respectively. 20(S)-Ginsenoside Rh2 was the active ingredient obtained by biomembrane using as a new quality control maker for SGHDP. Conclusion The developed method is accurate and reliable for the determination of three ginsenosides in SGHDP, and provides a new reference for quality control of SGHDP. 20(S)-Ginsenoside Rh2 is a immobilization component of red cell membrane, speculated to be the active ingredient of SGHDP, which is in consistent with previous studies on antitumor and antidepression.

Values of different fungal infection risk scoring methods for the early diagnosis of invasive Candida infection / 中国感染控制杂志

Objective To compare diagnostic value of four fungal scoring methods in invasive Candida infection,provide evidence for early diagnosis and treatment of invasive Candida infection.Methods High-risk patients with invasive Candida infection in the intensive care unit(ICU) in a hospital from 2011 to 2016 were analyzed retrospectively.According to diagnostic criteria,patients were divided into four groups:non-infection group,suspected infection group,clinically diagnosed group,and confirmed group,patients were conducted multi-diseases risk assessment (MDRA) score,invasive fungal infections risk scoring system (IFIRSS) score,Sevilla score,and Candida score,diagnostic value of four scoring methods for invasive Candida infection were evaluated.Results There were 275 high-risk patients,138 in non-infection group,63 in suspected infection group,and 74 in infection group(clinically diagnosed group:n =64;confirmed group:n =10).The age and length of hospital stay in the infection group were all higher than non-infection group (both P＜0.05).74 strains of Candida were isolated from 74 infected patients,mainly Candida albicans (n =60,81.1％).Positive rates for MDRA score,Candida score,Sevilla score,and IFIRSSscore were 41.5％(n =114),30.2％(n =83),15.3％(n =42),and 8.4％ (n =23) respectively.Of four MDRA scoring methods,MDRA had the higher sensitivity(Se,59％) but lowest specificity(Sp,66％);IFIRSS had higher Sp(91％) but very low Se (9％);Sevilla score had the highest Sp (96％)and higher Se(45％);Candida score had the highest Se(68％) and higher Sp (90％).Conclusion Sevilla score has higher Se and Sp,which can be used in early diagnosis of invasive Candida infection;Candida score has the highest coincidence with clinical diagnostic criteria for invasive Candida infection,both Se and Sp are high,which is of great value for early diagnosis of invasive Candida infection.

Recent development of non-steroidal anti-inflammatory drugs on the neuro-inflammation of Alzheimer's disease / 药学学报

Neuropathological, clinical epidemiology and animal models studies provide clear evidence for the activation of neuroinflammation in Alzheimer's disease (AD), and long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is linked with reduced risk to develop the disease. But the clinical trials got a negative outcome with traditional NSAIDs treating AD. The therapeutic effects of NSAIDs on Alzheimer's disease are still not clear based on the present research. Profound study for anti-inflammatory mechanisms and standardized clinical trials are needed. As cause and effect relationships between neuroinflammation and AD are being worked out, the challenge is how to realize the effect of traditional NSAIDs on treating AD.

Efficacy observation on Jin's three-needle therapy for allergic rhinitis of lung qi deficiency and cold syndrome / 中国针灸

<p><b>OBJECTIVE</b>To compare the clinical efficacy in the treatment of allergic rhinitis (AR) of lung qi deficiency and cold syndrome between Jin's three-needle therapy and western medication.</p><p><b>METHODS</b>Sixty-six patients were randomized into an acupuncture group and a western medication group, 33 cases in each one. In the acupuncture group, acupuncture was applied at three-nose points [Yingxiang (LI 20), Shangyingxiang (EX-HN 8) and Yintang (GV 29); Cuanzhu (BL 2) was added for frontal headache] and three-back points [Dazhu (BL 11), Fengmen (BL 12) and Feishu (BL 13)], once every day. Ten treatments made one session. Two sessions of treatment were required. In the western medication group, desloratadine oral suspension was prescribed, 5 mg each time, once a day, for 20 days. The scores of the symptoms and physical signs in AR patients as well as the clinical efficacy were observed between the two groups.</p><p><b>RESULTS</b>The total effective rate was 93.9% (31/33) in the acupuncture group, which was better than 72.7% (24/33) in the western medication group (P < 0.05). After treatment, the scores of AR symptoms and physical signs as well as the total score were all reduced compared with those before treatment in the two groups (all P < 0.01). The score of every item in the acupuncture group was lower than that in the western medication group after treatment (score of symptoms: 4.70 +/- 2.07 vs 6.55 +/- 2. 69, score of physical signs: 0.85 +/- 0.67 vs 1.45 +/- +0.62, total score: 5.36 +/- 2.70 vs 8.00 +/- 2.91, all P < 0.01).</p><p><b>CONCLUSION</b>Jin's three-needle therapy achieves superior efficacy on AR of lung-qi deficiency and cold syndrome, which is better than desloratadine oral suspension.</p>

An epidemiological investigation on a food-born outbreak of noroviru caused by Sydney 2012 G II.4 strain / 中华流行病学杂志

<p><b>OBJECTIVE</b>To identify the source of infection, route of transmission and risk factors related to a cluster of acute gastroenteritis cases in a university of Guangzhou.</p><p><b>METHODS</b>Cases were identified according to the definition. Descriptive epidemiological approaches and case-control study designs were employed in the analysis. All the samples were tested for norovirus by RT-PCR. Positive samples were subjected to both nucleotide sequence and homology analysis.</p><p><b>RESULTS</b>A total of 141 cases related to norovirus gastroenteritis were identified in January 8 to 21, 2013, with the attack rate as 8.5 per thousand (141/16,600). The peak in morbidity was seen on January 8 to 9. No clustering was found in different classes or dormitories. Results from the case-control study revealed that early cases were infected in Restaurant A (OR = 3.46, 95% CI: 1.07-11.16) and the cold shredded chicken set meal (OR = 17.82, 95% CI: 4.46-78.17) served at lunch (OR = 4.34, 95% CI: 1.18 -17.37) on January 7 was under suspicion. A total of 266 samples, including rectal swabs from the patients and kitchen wokers, leftover food and environmental swabs, were collected. Twenty-one samples (collected from 17 persons) were positive for norovirus by RT-PCR. About 29.6% (8/27) of the kitchen workers in the Restaurant A were tested positive for the virus. The pathogen was identified as the new norovirus genotype II.4 variant, termed Sydney 2012. The virus strains isolated from the patients among student and staff and the kitchen workers were 100% identical in their nucleotide sequence.</p><p><b>CONCLUSION</b>This was the first reported acute gastroenteritis outbreak caused by the new norovirus genotype II.4 variant, Sydney 2012, which showed that the food was contaminated by the asymptomatic kitchen workers who carried the virus.</p>

Risk evaluation on H7N9 avian influenza in Guangzhou, China / 中华流行病学杂志

<p><b>OBJECTIVE</b>We conducted both quick surveillance and evaluation programs within one week after the novel H7N9 influenza cases had been released by the Ministry of Health (MOH), to get the basic information on H7N9 virus in Guangzhou.</p><p><b>METHODS</b>We sampled live birds from food markets and the natural habitat of birds to detect H7N9, H5 and H9 viruses. We interviewed workers from both markets and natural habitats. We also reviewed records on pneumonia patients with unknown causes from the surveillance system, to find clues related to the identification of severe pneumonia.</p><p><b>RESULTS</b>We sampled 300 specimens from 49 stalls in 13 food markets and a natural habitat but none showed H7N9 positive result. A chopping block was detected positive of carrying H5 avian influenza virus, while another 4 specimens including a chicken cage, a duck cage, a chopping block and a pigeon cage were detected positive of carrying H9 avian influenza virus. In the past month, no sick, dead birds or ILI cases among the workers were discovered. 21.2% (7/33) of the stalls did not follow the set regulations for prevention. 10.3% (4/39) of the stalls had the cages cleaned, 4 days after the inspection. 3.7% (2/54) of the workers wore masks and 40.7% (22/54) of them wore gloves during the slaughtering process. 102 bird feces specimens were tested negative on H7N9 virus. No pneumonia cases with unknown reason were identified. From April 3(rd) to 17(th), we found 26 severe pneumonia cases but with negative results on influenza A (H7N9).</p><p><b>CONCLUSION</b>According to the data and information from 1) lab tests, 2) pneumonia cases with unknown reasons under the surveillance system, 3) the identification of severe pneumonia cases, and 4) preventive measures and actions taken by the workers, we inferred that no H7N9 virus or related cases were found prior to April in Guangzhou. However, the risk of H7N9 epidemic does exist because of the following reasons:1) improper market management process, 2) negligent behavior of the workers and 3) potential trend of the national situation, suggesting strategies related to poultry markets management, health education and preventive measures against the avian influenza need to be strengthened.</p>

Investigation on the source of infection regarding an avian influenza (H5N1) case in Hong Kong that returning from Guangzhou / 中华流行病学杂志

Objective We conducted an epidemiologic investigation to determine the source of infection on an avian influenza (H5N1) case who returned from Guangzhou,in Hong Kong.Methods Data related to epidemiologic investigation,medical observation on close contacts,Syndromic Surveillance on poultry salesmen,emergency monitoring,detection of the samples,source tracing on potential Avian influenza virus (H5,H7,H9) infected people,situation on environment pollution by avian influenza virus in the markets etc.were gathered.The determination of infection source was through comparing the different genes between the case and positive environmental samples.Results The infected case witnessed the procedure of how a live duck was killed,in market A in Guangzhou during May 17th to 19th.The case was diagnosed as respiratory tract infection in 2 Third-grade-Class A hospitals in Guangzhou on May 23th and 24th.The diagnosis was made as Avian influenza cases on May 26th after going back to Hong Kong.23 close contacts and 34 markets poultry salesmen did not show any ILI related symptoms.However,2 poultry salesmen from the markets nearby the place where the Avian influenza case stayed,were detected having positive H9 avian influenza antibody,with the H9 positive rate as 6.06％ (2/33).Among the environmental samples in the 2 markets nearby home of the patient,chopping block was found to have carried H5,with positive rate as 9.8％(5/51) while poultry cage was found to carry H9,with the positive rate as 2.0％(1/51).A H5 positive sample was found with clade 2.3.2.1,same to the case,from a chopping block at the market B where the sources of poultry was the same as market A.Conclusion The source of infection seemed to come from the markets in Guangzhou,that calling for the strengthening of poultry market management,for avian influenza prevention.History related to contact of poultry should be gathered when a diagnosis of respiratory tract infection was made.Timely sampling and testing should be made to improve the sensitivity of diagnosis.

Imaging and biodistribution of 99Tcm labeled cyclic RGD peptide in nude mice with xenografted lung adenocarcinoma / 中华核医学杂志

ObjectiveTo synthesize 99Tcm labeled hydrazine-nicotinamide ( HYNIC)-c (RGDfK)and evaluate its biodistribution and imaging in the severe combined immunodeficiency (SCID) nude mice bearing human lung adenocarcinoma.Methods( 1 )Tcm-HYNIC-c(RGDfK) was prepared by a two-step method using tricine and ethylenediamine diacetate (EDDA) as coligands and HYNIC as the dual functional chelator.The bioactivity of 99Tc m-HYNIC-c (RGDfK) was measured by cell binding experiments.(2) The nude mice bearing human A549 lung adenocarcinoma were randomly divided into 7 groups with 5 in each group.The 7 th group was the competitive inhibition control group and was administrated 100 μg HYNIC -c (RDGfK) 30 min earlier before the injection of 99Tcm-H Y N IC-c ( RGDfK ).The nude mice were scanned at 0.5,1,2,4,8 and 12 h respectively after intravenous injection of 7.4 MBq 99Tcm-HYNIC-c(RGDfK).The biodistribution of the agent was measured as ％ ID/g.The uptake ratio of tumor to muscle (T/NT) was also measured by placing ROI on 99Tcm-HYNIC-c(RGDfK) SPECT imaging.(3)Gamma imaging was performed in 6 mice including 3 in the competitive inhibition control group at 0.5,1,2,4,8 and 12 h post injection.ResultsThe labeling yield of 99Tcm-HYNIC-c(RGDfK) was more than 90％,and the radiochemical purity was more than 95％.99Tcm-HYNIC-c(RGDfK) can specifically bind with A549 adenocarcinoma cells with a binding rate up to 36.14％.Biodistribution study showed that the uptake in the kidney was above 20 ％ ID/g during 0.5 - 8 h post injection.The ％ ID/g in tumor was 10.52 ± 1.48 at 0.5 h,17.26 ±2.81 at 8 h,and 8.93 ±0.90 at 12 h.However,the ％ ID/g in tumor was only 2.29 ±0.85 in the competitive inhibition control group at 0.5 h.The highest T/NT was 6.87 at 8 h by the ROI analysis.Xenograffted tumors could be visualized at 1 h and delineated more clearly from 4 to 8 h post injection of 99Tcm-HYNIC-c(RGDfK).Conclusions99 Tcm-HYNIC-c (RGDfK) can be readily synthesized.Its binding with A549 lung adenocarcinoma cells is specific and the binding rate is high.

The distribution and scintigraphy of 99Tcm labeled NGR-interferon-alpha2a in tumor bearing mice / 中华核医学杂志

Objective To sythesize 99Tcm labeled asparagine-glycine-arginine (NGR)- interferon (INF)-α2a and investigate its biodistribution by scintigraphy in tumor bearing mice. Methods NGR-INFα2a was labeled with 99Tcm by a two-step method. Ethylenedicysteine (EC) and MDP were used as bifunctional and transferring chelating agents. The bioactivities of 99Tcm-NGR-IFN-EC-NGR-IFN-α2a, EC-NGRIFN-α2a and NGR-IFN-α2a were compared using least significant difference t-test. The hepatoma bearing mice models were established by subcutaneous injection of MHCC97-H cells. The mice were randomly divided into eight groups and 7.4 MBq 99Tcm-NGR-IFN-α2a was injected via the tail vein. The tissue uptake of the radiolabeled compound was measured as % ID/g. The scintigraphy was performed at 0.5, 1, 2, 4,6, 8, 12 and 24 h after injection. ROI were drawn around tumor and non-tumor tissue and the radioactivity ratio of T/NT was calculated. Results Both the labeling efficiency and radiochemical purity of 99Tcm-EC-NGR-IFN-α2a were more than 90%. The radiochemical purity was 71% after 24 h in saline. The bioactivity showed no significant difference among three compounds (t = 0.416, 0. 120 and 1. 300, all P >0.05). The tracer was mainly excreted through alimentary and urinary tract within 24 h after injection. The peak values of % ID/g in kidney, liver, interstinal tract and tumor were 41.5 ± 8.0_ (at 8 h), 31.3 ± 5.0(at 6 h), 36.0 ± 7.8 (at 6 h), 43.0 ± 4.8 (at 4 h), respectively. The tracer was cleared quickly from the blood and the highest T/NT ratio was 16.5. The optimal imaging time ranged from 4 to 8 h after injection. Conclusions The sythesis of 99Tcm-NGR-IFN-α2a is applicable and it may be used as a potential tumor imaging agent.

Genetic variability in adapter proteins with APPL1/2 is associated with the risk of coronary artery disease in type 2 diabetes mellitus in Chinese Han population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Adaptor proteins containing PH domain, PTB domain, and leucine zipper motif 1 and 2 (APPL1/2) play a key role in cell proliferation in many tissues. APPL1 or APPL2 as an adaptor for adiponectin receptors mediates the signaling pathway of adiponectin which acts as an anti-atherosclerotic adipokine. This study aimed to investigate whether genetic variations in the APPL1/2 genes affect the risk of coronary artery disease (CAD) in Chinese patients with type 2 diabetes mellitus (T2DM).</p><p><b>METHODS</b>Seven haplotype-tagging single nucleotide polymorphisms (tag-SNPs) were selected from CHB HapMap database (Phase II) and total 203 CAD-positive cases and 106 CAD-negative controls with T2DM were genotyped for the 7 tag-SNPs by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.</p><p><b>RESULTS</b>The minor allele G of rs4640525 at APPL1 locus was protective from CAD in patients with T2DM, with the carriers of genotype CC at higher risk of CAD compared with non-carriers (OR = 2.830, 95%CI 1.285 - 6.230, P = 0.010; OR' = 4.992, 95%CI = 1.758 - 14.173, P' = 0.003, after adjustment for the other known CAD risk factors); the homozygotes of AA at rs11112412 in APPL2 gene had higher risk of CAD compared with those of GG (adjusted OR' = 5.697, 95%CI 1.006 - 32.257, P' = 0.049).</p><p><b>CONCLUSION</b>Genetic variation(s) in APPL1/2 may be associated with CAD risk in T2DM in Chinese population.</p>

Long-term effect of acupuncture on quality of life in patients with early stage of stroke / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the long-term effects of acupuncture on quality of life in patients with early stage of stroke.</p><p><b>METHODS</b>Eighty patients were randomly assigned to the acupuncture group and the control group, 40 in each. All received conventional Western medical treatment, but for patients in the acupuncture group, acupuncture was applied additionally immediately from 48 h after patients' life signs were stabilized. Curative effects were evaluated with scores of SF-36, function independent measure (FIM) and NIHSS.</p><p><b>RESULTS</b>Effect evaluated immediately after acupuncture operation showed that all the scores in the acupuncture group, except score of recognition function in FIM, and scores of body pain and physical function in SF-36, were improved more significantly than those in the control group (P < 0.05). The effectiveness improved continuously in the 6-month period after stroke in both groups, but more superiority was shown in the acupuncture group in aspects of emotional function, social function and mental health by SF-36 (P < 0.05).</p><p><b>CONCLUSION</b>Early applying acupuncture could raise the physical, social, and psychological functions of stroke patients. Although the effects might decrease to some extent later, acupuncture still showed markedly effect on patients' psychological and social functions as well as on their life satisfaction.</p>

Clinical Features and Risk Factors of Elderly Patients with Post-stroke Hypertension / 中国康复理论与实践

@#ObjectiveTo investigate the clinical features and risk factors of elderly hospitalized patients with post-stroke hypertension (PSH).MethodsThe data including sex, age and blood pressure of 300 elderly PSH patients were analyzed retrospectively to find out the influence factors related to PSH.ResultsCompared with younger patients, the elderly patients had lower incidence of limb paralysis, disturbance of consciousness, while high frequency of headache and emesis on admission; hypertension, diabetes, smoking and alcohol abuse were significantly less frequent, while coronary heart disease and pneumonia were more common in elderly patients. Blood pressure especially systolic pressure of elderly PSH patients raised obviously .ConclusionElderly stroke patients have distinctive risk factors and clinical features, which are different from younger patients.

Investigation on release model of insoluble drug in hydroxypropyl methycellulose matrix tablets / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the release model of insoluble drug carbamazepine (CBM) based on HPMC matrix tablets.</p><p><b>METHODS</b>CBM release profile from matrices and HPMC erosion rate were determined.</p><p><b>RESULT</b>The mathematical model by matrix erosion rate and drug release from HPMC K15M were established for the fractional HPMC and CBM released as M(P(t))/M(P(infinity))=-[0.8095ln((t))+1.2775]Meq((-0.0622t-0.305)) and M(d(t))/M(d(infinity))=-[0.1891t-0.1294]Meq(-0.9326). In comparison with the data of HPMC K4M matrix erosion and CBM release from HPMC K4M matrices, theoretical value agreed well with experimental data.</p><p><b>CONCLUSION</b>The two mathematical models can be satisfactorily applied to insoluble drug release, which is governed by matrix erosion.</p>