Dissolution behavior of aripiprazole tablets based on near infrared spectroscopy / 药学实践杂志

Objective To establish a near infrared (NIR) quantitative model for the dissolution behavior of aripiprazole tablets. Methods The NIR spectra of aripiprazole tablets were collected and the dissolution tests were performed to determine the dissolution of each tablet at 3, 6, 9, 12, 15 and 30 min. The near infrared spectra regions of 4 000.00-4 396.90, 5 326.43-12 000.00 cm−1 were pretreated by Savitzky-Golay smoothing filter, and the dissolution behavior model was established by partial least squares method. Results The root mean square error of calibration (RMSEC) and the root mean square error of prediction (RMSEP) at different time points were analyzed. RMSEP was lower than 8%. The calibration correlation coefficient (RC) and the prediction correlation coefficient (RP) at different time points were above 0.95 (except for the point of 6 min). There was a good correlation between the NIR spectrum and the dissolution at each time point. Conclusion NIR spectroscopy could predict the dissolution behavior of aripiprazole tablets, which lays a foundation for online quality monitoring of tablets by NIR spectroscopy.

Metabolic Disease Management Guideline for National Metabolic Management Center(2nd edition) / 中华内分泌代谢杂志

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Distribution characteristics of special types of diabetes mellitus in Chinese population: A literature-based analysis from 2011 to 2021 / 中华内分泌代谢杂志

Objective:To analyze the distribution characteristics of special types of diabetes in China, in order to provide a theoretical basis for the diagnosis and treatment of special types of diabetes.Methods:Pubmed, CNKI, and WanFang Data were searched for the case reports and clinical studies of special types of diabetes in China from 2011 to 2021. After independent literature screening by 2 researchers according to the inclusion and exclusion criteria, diseases and the number of corresponding cases included were extracted for statistics. The etiological composition and disease characteristics of three subtypes of special type diabetes were analyzed.Results:A total of 613 articles(7 377 patients)were included and roughly divided into eight subtypes of special type diabetes according to etiological classification for disease composition analysis. The results by ratio in descending order were as follows: mono-genetic gene defects in islet β-cell function, pancreatogenic diabetes, diabetes induced by drugs or chemicals, endocrine disease, mono-genetic gene defects in insulin action, other genetic syndromes associated with diabetes, infection, and uncommon immune-mediated diabetes. The disease composition of the three subtypes of special types of diabetes that we focused on were mono-genetic gene defects in islet β-cell function(50.21%), pancreatogenic diabetes(35.65%), and mono-genetic gene defects in insulin action(1.56%). The composition analysis of the special types of diabetes in each subtype showed that neonatal diabetes mellitus(NDM, n=1 749, 23.71%)and maturity onset diabetes in young(MODY, n=1 554, 21.07%)accounted for the largest proportions. According to the composition analysis of each subtype of MODY patients, the top three subtypes were MODY2(50.89%), MODY3(16.03%), and MODYX(8.91%). In addition, taking MODY as an example, patients with de novo mutations(DNMs)and(or)new mutation sites were summarized and analyzed. The results revealed 31 MODY patients with DNMs(1.99%) and 339 MODY patients with new mutation sites(21.81%). Conclusions:According to the literature analysis, NDM and MODY represent the largest proportion of patients with special type diabetes in China. MODY2 patients make up the largest proportion of MODY patients. In addition, diabetic patients carrying DNMs and(or)new mutation sites should be taken seriously.

Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study / 대한뇌졸중학회지

Background@#and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). @*Methods@#We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. @*Results@#Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. @*Conclusion@#The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Association between hemoglobin glycation index and 5-year major adverse cardiovascular events: the REACTION cohort study / 中华医学杂志(英文版)

BACKGROUND@#The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China.@*METHODS@#A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1-Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups.@*RESULTS@#The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors ( χ2 = 29.5, P <0.001). After adjustment for potential confounders, subjects with HGIs ≤-0.75 or >0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027-2.069) and 2.222 (95% CI, 1.641-3.026) compared to subjects with HGIs of >-0.75 and ≤-0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤-0.75 (OR, 1.540 [1.039-2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392-2.890]; P <0.001) compared to those with HGIs of ≤-0.75 or >0.82 after adjustment for potential confounders.@*CONCLUSIONS@#We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk.

Small-molecule anti-COVID-19 drugs and a focus on China's homegrown mindeudesivir (VV116) / 医学前沿

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.

Study on the dynamic variation of the secondary metabolites in Viscum coloratum using targeted metabolomics / 中国天然药物

Viscum coloratum (Kom.) Nakai is a well-known medicinal plant. However, the optimal harvest time for V. coloratum is unknown. Few studies were performed to analyze compound variation during storage and to improve post-harvest quality control. Our study aimed to comprehensively evaluate the quality of V. coloratum in different growth stages, and determine the dynamic variation of metabolites. Ultra-performance liquid chromatography tandem mass spectrometry was used to quantify 29 compounds in V. coloratum harvested in six growth periods, and the associated biosynthetic pathways were explored. The accumulation of different types of compounds were analyzed based on their synthesis pathways. Grey relational analysis was used to evaluate the quality of V. coloratum across different months. The compound variation during storage was analyzed by a high-temperature high-humidity accelerated test. The results showed that the quality of V. coloratum was the hightest in March, followed by November, and became the lowest in July. During storage, compounds in downstream steps of the biosynthesis pathway were first degraded to produce the upstream compounds and some low-molecular-weight organic acids, leading to an increase followed by a decrease in the content of some compounds, and resulted in a large gap during the degradation time course among different compounds. Due to the rapid rate and large degree of degradation, five compounds were tentatively designated as "early warning components" for quality control. This report provides reference for better understanding the biosynthesis and degradation of metabolites in V. coloratum and lays a theoretical foundation for rational application of V. coloratum and better quality control of V. coloratum during storage.

Interval linear quadratic regulator and its application for speed control of DC motor in the presence of uncertainties.

An analytical investigation of a DC motor with interval uncertainties is performed in this study and a new approach by interval analysis is suggested for optimal control of the system. The main advantage of using an interval model for uncertainties is that makes the system independent from the probability distribution models of the system; therefore, it can be analyzed by only having information about minimum and maximum bounds. Here, the interval analysis deals with linear quadratic feedback control (LQR) to simulate and optimal control of the DC motor in the realistic state. To do this, the Pontryagins principle is used to solve the interval linear quadratic regulator to obtain the essential conditions, and thus, they have been reconstructed as ordinary differential equation by applying several algebraic manipulations. Afterward, by solving the interval nonlinear system of the ODE, the confidence interval for the feedback controller is achieved. The confidence interval is to guarantee the solution which is included in it. The Chebyshev inclusion approach is applied here to find solution for the ODE system with uncertainties. A comparison of the step response of the suggested approach with the centered approach and Monte Carlo methods a statistical approach is performed. The simulation results indicated that the suggested approach retains tighter and more sensible results than the Monte Carlo method.

Effects of growth hormone replacement therapy on glucose and lipid metabolism in patients with hypopituitarism / 中华内分泌代谢杂志

Objective:To investigate the effect of growth hormone replacement therapy(GHRT) on glucose and lipid metabolism in patients with hypopituitarism.Methods:Clinical data of patients with hypopituitarism who received GHRT in Department of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2016 to February 2020 were retrospectively analyzed. The patients were divided into normal glucose regulation(NGR) group and impaired glucose regulation(IGR) group according to their glucose metabolism status before GHRT. The changes of the characteristics of glucose metabolism before and after GHRT were analyzed.Results:A total of 30 patients aged(23.0±5.2) years were included, 23 patients in NGR group and 7 patients in IGR group. After 12 months of GHRT, there were no significant changes in fasting plasma glucose(FPG), 2-hour postprandial plasma glucose(2hPG), and insulin sensitivity index(ISI) in both groups(all P>0.05), while homeostasis model assessment insulin resistance(HOMA-IR) in IGR group was significantly decreased compared with that before GHRT( P<0.05). None of the patients in NGR group progressed to IGR or diabetes mellitus, and none of the 7 patients in the IGR group progressed to diabetes mellitus, while 4 of them recovered from impaired glucose tolerance(IGT) to NGR. Triglyceride, total cholesterol, and low density lipoprotein-cholesterol levels were all significantly decreased in two groups(all P<0.05). Multivariate linear regression analysis showed that the increase of body mass index was an independent risk factor for the increase of FPG and 2hPG( P<0.05). Conclusion:12-month GHRT significantly improved their blood lipid profiles in patients with hypopituitarism without adversely affecting glucose homeostasis.

Unadjusted and adjusted fracture risk assessment tool and the hip fracture risk in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:To evaluate and compare the clinical value of unadjusted fracture risk assessment tool(FRAX) and adjusted FRAX in predicting the risk of hip fracture in patients with type 2 diabetes(T2DM).Methods:In this 10-year retrospective cohort study, 1 730 patients with T2DM were collected from August 2009 to July 2013. The 10-year risk of hip fracture was calculated using the China FRAX model. Hip fracture events during the follow-up period were collected through electronic medical records and telephone interviews. The value of FRAX and adjusted FRAX in predicting the risk of hip fracture in T2DM patients was evaluated from two aspects of discrimination and calibration. Cox regression model was used to investigate the relationship between diabetes related factors and hip fracture.Results:A total of 39 participants(2.3%) experienced hip fracture during a median follow-up of 10 years. The area under the curve of unadjusted FRAX was 0.760, but the calibration ability was poor [calibration χ2: 75.78, P<0.001; calibration ratio(observation/prediction): 3.97(95% CI 2.76~5.17)]. There was no significant improvement in calibration ability of adjusted FRAX. After adjustment for unadjusted or adjusted hip fracture probability calculated by FRAX(FRAX-HF), duration, estimated glomerular filtration rate, insulin use, cerebrovascular diseases, and diabetic peripheral neuropathy were significantly associated with an increased risk of hip fracture( P<0.05). Conclusion:The FRAX tool significantly underestimated the risk of hip fracture in T2DM patients, and there was still significantly underestimation after adjustment due to the failure to eliminate the influence of diabetes-related factors such as disease duration and peripheral neuropathy.

Establishment of online quantitative model for moisture content determination of hydroxychloroquine sulfate particles by near infrared spectroscopy / 药学实践杂志

Objective To establish an online quantitative analysis model for moisture content assay of hydroxychloroquine sulfate particles by near infrared (NIR) spectroscopy. Methods The NIR spectra were collected in real time when the material particles were dried in the fluidized bed. Meanwhile the water content of the particles was measured with the standard moisture tester. The multiplicative signal correction (MSC) and first derivative followed by Karl Norris smoothing were used for spectra pretreatment. Two spectral range (4 935−5 336 cm−1 and 6 911−7 297 cm−1) were selected for the quantitative model with the partial least squares (PLS) regression. Results The quantitative calibration model had good correlation coefficients with Rc value=0.952 9 and Rp value=0.936 6. The root mean square error of calibration (RMSEC) was 0.408 and the root mean square error of prediction error (RMSEP) was 0.435. The ratio of standard deviation of validation set to prediction standard deviation (RPD) was 5.18. There was no significant difference between the predicted value and the reference value by t test when the established model was applied in large-scale production. Conclusion The online model established for monitoring water content has high accuracy and stability, which can be applied in industrial scale process to monitor the particle moisture in real time.

Generalized lipodystrophy type 1 due to compound heterozygous mutation of AGPAT2 gene: One case report and literature review / 中华内分泌代谢杂志

Congenital generalized lipodystrophy type 1 (CGL1) is an autosomal recessive genetic disease caused by mutations in AGPAT2 gene. The main clinical mainifestations include body subcutaneous fat loss, muscle hypertrophy, obvious subcutaneous veins, pseudoacromegaly, hirsutism, and acanthosis nigricans. What′s more, CGL1 is always accompanied by metabolic diseases. Therefore, it is easily misdiagnosed as metabolic syndrome, type 2 diabetes, polycystic ovary syndrome, acromegaly, or Cushing′s syndrome. Meanwhile, it is difficult to distinguish it from partial lipoatrophy syndrome. In this article, we present clinical and molecular characteristics of a patient with CGL1 and review mutations reported in literature to replenish current knowledge about this orphan disease.

Clinical diagnosis and treatment of nerve mediated syncope in children and adolescents / 国际儿科学杂志

Nerve mediated syncope is the most common type of syncope in children, which is a kind of functional cardiovascular disease, including vasovagal syncope(VVS), postural tachycardia syndrome(POTS), orthostatic hypotension(OH), orthostatic hypertension(OHT), situational syncope(SS)and carotid sinus syndrome(CSS). Among them, VVS and POTS are the main ones, accounting for about 95% of children with nerve mediated syncope.Nerve mediated syncope affects the children′s daily life, threatens their physical and mental health, and causes anxiety among the parents.Therefore, there have been lots of researches on this disease in recent years.This paper reviewes the research progress of clinical features, clinical diagnosis and treatment of VVS, POTS, OH and OHT in children and adolescents.

Series interpretation to Chinese Expert Consensus on the Diagnosis and Treatment of Acromegaly(2020)(Part 1): Genetic causes of acromegaly / 中华内分泌代谢杂志

Acromegaly is a commonly functional pituitary tumor. Standardized managements are crucial for the patients. Chinese Expert Consensus on the Diagnosis and Treatment of Acromegaly(2020) has been updated in 2020 based upon latest advance. This essential introduction about genetic causes would further guide and standardize the management of acromegaly.

Numerical Model for Calculating Active and Passive Properties of Muscles with High Strain Rate / 医用生物力学

Objective On the basis of explicit dynamics calculation theory, a numerical model for calculating active and passive properties of muscles with high strain rate was proposed. Methods In the process of calculating the motion equation of muscle element with high strain rate, Hill’s three-factor muscle model with high strain rate was introduced into the noda force formula to modify the node force in each time step. Results As Hill’s three-factor muscle model was introduced in numerical calculation, the muscle element had the passive characteristics of the general structural constitutive model and its proprietary active characteristics. Conclusions The research findings will contribute to numerical calculation for dynamic response and damage of muscles with high strain rate.

Interval-based LQR strategy for optimal control of proton exchange membrane fuel cell system with interval uncertainties.

Proton exchange membrane fuel cells (PEMFC) are a type of the increasingly developed sustainable energy systems which have been turned into one of the most popular of them in the last decade. The performance of these types of fuel cells is the best among the others; however, they can be better by an authentic control to maintain in the maximum efficiency in the operative points during the current ripples. To do this and also to improve the value of the output voltage, the two-phase interleaved boost converter is utilized. Since boost converter has uncertain parameters and disturbances in their essence, using the ordinary methods for the control of them can ignore some of the principal parameters. In this study, a new technique is utilized for optimal control of the proton exchange membrane fuel cells with interval uncertain parameters. Here, we consider the uncertainties in the converter inherent. Because of considering the uncertainties in the system, controllability of the system is first testified based on interval arithmetic. Then, an extended version of the linear quadratic regulator strategy using interval analysis is employed for achieving a reliable and optimal solution. Chebyshev inclusion method is utilized for solving the Pontryagins problem of the LQR problem. Eventually, by solving the interval version of the Riccati equations, the robust range for optimal control of the PEMFC is obtained. The results of the proposed system are finally compared with Monte Carlo method for showing the efficiency of the presented technique.

Clinical characteristics of ocular toxocariasis in adults / 中华眼底病杂志

Objective:To observe the clinical characteristics of adult patients with ocular toxoplasmosis (OT).Methods:This study was a retrospective clinical trial. Among the 83 consecutive OT patients diagnosed in the Zhongshan Eye Center of Sun Yat-Sen University, 14 patients (16.9%, adult group) aged ≥18 years were included in the study from January 2017 to December 2019. A total of 14 OT patients (children group) aged less than 18 years who had consecutive visits from July to December 2019 were selected as controls. All patients underwent BCVA, slit lamp microscope, fundus color photography, and B-mode ultrasound examination. Eighteen cases underwent UBM examination, including 6 and 12 cases in the adult group and child group respectively; 23 cases underwent FFA examination, including 12 and 11 cases in the adult group and child group respectively. Snellen visual acuity chart was used for BCVA examination, which was converted into logMAR visual acuity in statistics. We compared the two groups of patients' residence (urban or rural), history of contact with dogs and cats, main symptoms, reasons for treatment, course of disease, and clinical and imaging characteristics and so on. For measurement data conforming to normal distribution, t-test was performed for comparison between groups; for Skewness distribution measurement data, rank sum test was performed for comparison between groups. Results:Compared with the adult group and the child group, there was no significant difference in the canine-cat contact history ( Z=2.661, P=0.257) and the time from first diagnosis to diagnosis ( t=-0.186, P=0.351); compared with the children group and the adult group, the patient's living environment was mainly urban, and the course of disease was significantly shorter ( Z=-2.005), and the difference was statistically significant ( P=0.047). The logMAR BCVA of the adult group and the child group were 0.81±1.08 and 2.08±1.30, respectively, and the difference was statistically significant ( Z=-2.811, P=0.004); compared with the child group, the adult group had lighter vitreous opacities, but the difference was statistical significance ( Z=7.847, P=0.048). FFA examination revealed 20 cases of "fern-like" leakage of retinal capillaries. Among them, the adult group and child group were 10 (83.3%, 10/12) and 10 (90.9%, 10/11) cases respectively. Conclusions:Adult patients account for 16.9% of OT patients. Compared with children, adult patients mostly live in towns or cities, have a short course of disease, good vision at first diagnosis, and mild inflammation or hyperplasia of the vitreous cavity. FFA is helpful for the diagnosis of adult OT.

Relationship between famine exposure in early life and type 2 diabetes mellitus in adulthood / 中华内分泌代谢杂志

Objective:To investigate the correlation between exposure to famine in early life and later risk of type 2 diabetes in adulthood.Methods:A cluster sampling method was used to include 8 868 residents who were lived in the Jiading community of Shanghai during the Great Famine from 1959 to 1962 in China. Subjects were divided into non-exposed group, fetal exposure group, childhood exposure group, and adolescent exposure group. Logistic regression model was used to analyze the relationship between famine exposure in early life and the risk of type 2 diabetes in adulthood. Results:Famine exposure during childhood and adolescent both increased the risk of developing type 2 diabetes in adulthood in women. No significant correlation was observed in men. In subjects with less physical activity and lower education level, the risk of developing type 2 diabetes mellitus in adulthood was significantly higher in the famine-exposed group than that of non-exposed groupand the interactions were statistically significant.Conclusion:Early life famine exposure increases the risk of developing type 2 diabetes in adults, especially in women.

Advances and prospectives of metabolic chamber application in endocrine and metabolic diseases / 中华内分泌代谢杂志

The metabolic chamber system is a new-developed method of energy metabolism examination by indirect calorimetry. Recently, metabolic chambers have been applied in energy expenditure affected by the changes of diet, sleep and physical activities, and metabolic diseases such as obesity and type 2 diabetes mellitus, to underlie the potential mechanisms. This review is aimed to summarize the applications of metabolic chambers in China and abroad in researches on energy metabolism involved in physiology, endocrine diseases and energy metabolism disorders. A more extensive use of metabolic chambers in clinical practice is well expected in the foreseeable big-data era.