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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.
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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.
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Viscum/chemistry , Plants, Medicinal/chemistry , Chromatography, Liquid , Mass Spectrometry , MetabolomicsABSTRACT
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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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The endangered medicinal plant Glehnia littoralis is one of the important natural source of furanocoumarin, which has been used as mucolytic, antitussive, antitumour and antibacterial. However, the genetic information of furanocoumarin biosynthesis in G. littoralis is scarce at present. The objective of this study was to mine the putative candidate genes involved in the biosynthesis pathway of furanocoumarin and provide references for gene identification, and functional genomics of G. littoralis. We carried out the transcriptome analysis of leaves and roots in G. littoralis, which provided a dataset for gene mining. Psoralen, imperatorin and isoimperatorin were detected in G. littoralis by high performance liquid chromatography analysis. Candidate key genes were mined based on the annotations and local BLAST with homologous sequences using BioEdit software. The relative expression of genes was analysed using quantitative real-time polymerase chain reaction. Further, the CYP450 genes were mined using phylogenetic analyses using MEGA 6.0 software. A total of 156,949 unigenes were generated, of which 9021 were differentially-expressed between leaves and roots. A total of 82 unigenes encoding eight enzymes in furanocoumarin biosynthetic pathway were first obtained. Seven genes that encoded key enzymes in the downstream furanocoumarin biosynthetic pathway and expressed more in roots than leaves were screened. Twenty-six candidate CYP450 unigenes expressed abundantly in roots and were chiefly concentrated in CYP71, CYP85 and CYP72 clans. Finally, we filtered 102 differentially expressed transcription factors (TFs) unigenes. The transcriptome of G. littoralis was characterized which would help to elucidate the furanocoumarin biosynthetic pathway in G. littoralis and provide an invaluable resource for further study of furanocoumarin.
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Objective:To evaluate the radiotherapy-related survival prognosis value of Rades score in patients with metastatic spinal cord compression (MSCC).Methods:The clinical data of 110 patients with MSCC who underwent radiotherapy from January 2010 to January 2014 in Cancer Hospital of the University of Chinese Academy of Sciences were retrospectively analyzed. The primary tumor was 36 cases of prostate cancer, 18 cases of myeloma/lymphoma, 15 cases of breast cancer, 7 cases of lung cancer, and 34 cases of other types of cancer. The survival status, overall survival time and Rades score were recorded. The influencing factors of survival prognosis and the relationship between the Rades score and survival prognosis were analyzed.Results:The 84.5% (93/110) patients had a radiotherapy dose of 20 Gy/5 times; 5.5% (6/110) patients (operated patients or myeloma/lymphoma patients) had a radiotherapy dose of 30 Gy/10 times. Thirty-seven cases were treated by surgery. The patients were followed up for (38.6 ± 15.2) months, and the overall survival period was (15.2 ± 0.5) months. Cox proportional hazards model analysis result showed that the primary tumor type, surgical treatment, combined chemotherapy and Rades score were the risk factors of survival prognosis in patients with MSCC ( P<0.05). Among the 110 patients, Rades score was 20 to 30 scores in 17 cases (group A), 31 to 35 scores in 40 cases (group B), and 36 to 45 scores in 53 cases (group C). The 6-month survival rate in group C was significantly higher than that in groups A and group B: 45.3% (24/53) vs. 0 and 27.5% (11/40), and there was statistical difference ( P<0.05). The 5-year survival rate in group C was 22.6% (12/53), and the 5-year survival rates in both groups A and group B were 0. Conclusions:Rades score is related to the survival prognosis of MSCC patients, and can assist in formulating radiotherapy programs for MSCC patients.
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Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has occurred in China. Higher risk of COVID-19 infection and worse prognosis were observed among patients with diabetes. There are rigorous challenges existing in terms of diabetes prevention and glycemic control in primary medical care during period of COVID-19. Here, expert recommendations were developed by Chinese diabetologists, healthcare providers, and public health administrators to improve the ability of primary health facilities and provide standardized basic public health and medical services throughout country. The main contents include basic requirements for management, workflow of health management, referral, treatment, and long-term follow-up.
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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.
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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.
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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.
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Delineation of the relationship between insulin resistance, β cell dysfunction, and obesity is crucial for the prevention and effective management of diabetes. Previous studies have indicated that, compared with type 2 diabetes in Caucasian, type 2 diabetes in East Asians is characterized primarily by β cell dysfunction rather than insulin resistance. This pathophysiological characterization of diabetes in East Asians is mainly derived from Japanese and Asian-American populations, whereas data from mainland China are scarce. Over the past four decades, China has witnessed a substantial rise in obesity, in parallel with the transitions from principally active lifestyles and calorie-restricted diets to sedentary life styles and energy-dense, western diets. Obesity is an insulin resistance state and the major factor driving the worldwide epidemic of diabetes. It is unknown whether, and if so how, obesity affects the two primary mechanisms, insulin resistance and β cell dysfunction, responsible for the development of diabetes in the Chinese population. Recently, the Lancet Diabetes & Endocrinology published an original research paper from the China Cardiometabolic Disease and Cancer Cohort Study (4C). From a public health perspective, the results of this study reinforce the urgency of tackling obesity as a major preventive strategy for the epidemic of type 2 diabetes in China.
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Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has occurred in China. Higher risk of COVID-19 infection and worse prognosis were observed among patients with diabetes. There are rigorous challenges existing in terms of diabetes prevention and glycemic control in primary medical care during period of COVID-19. Here, expert recommendations were presented by Chinese diabetologists, healthcare providers, and public health administrators to improve the ability of primary health facilities and provide standardized basic public health and medical services throughout the country. The main contents include basic requirements for management, workflow of health management, referral, treatment, as well as the long-term follow-up.