Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Codonopsis Radix， one of the bulk commodities， has been commonly used for tonification in clinical practice. Apart from the medicinal purpose， it can also be utilized as food. Among the multiple local varieties， the ones called "Luduiduoji" in Tibetan medicine cannot be neglected， which have frequently been adopted for diminishing inflammation and swelling， invigorating spleen and stomach， and tonifying Qi， etc. Considering its complex origins and frequent substitution by or confusion with other medicinal materials， this paper reviewed the Si Bu Yi Dian， Jingzhu Bencao， ministerial and local standards， modern literature on Tibetan medicine， and the results of field investigation in major Tibetan medicine hospitals and medicinal material markets of Sichuan， Qinghai and Tibet to figure out the name， original plants， medicinal parts， effects， and local varieties of Codonopsis Radix in Tibetan medicine. The results showed that the names of local varieties were diverse， many of which were transliterated into Tibetan， with "Luduiduoji" being most well-known. It was derived from 14 species in genus Codonopsis and one in Adenophora of family Campanulaceae， with Codonopsis foetens subsp. nervosa， C. thalictrifolia var. mollis， C. canescens， C. alpina， and C. pilosula being the main species. According to literature records， the roots， aerial parts， and whole plants could all be employed as medicine， but there were certain differences in their clinical applications. At present， in order to protect the medicinal resources， Tibetan medical workers mostly collect the aerial parts， which are applicable to patients with yellow water， rheumatism， Gamba disease， and leprosy. This literature review of local varieties for Codonopsis Radix and textual research on their original plants are of great significance for elevating the standard， accelerating the pharmacodynamic research， expanding the sources and promoting the rational use of Codonopsis Radix.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Classical famous prescription Dihuang Yinzi is widely used in modern clinical practice，and can treat many kinds of diseases，especially the diseases of nervous system in internal medicine. Its clinical effect is accurate，but it has not been converted into Chinese patent medicine preparations. Therefore，the authors have collected ancient traditional Chinese medicine（TCM） literatures of Dihuang Yinzi by the methods of bibliometrics，and selected and sorted out 254 pieces of effective data， involving 144 ancient books of TCM，and systematically summarized and analyzed the historical development origin，main treatment syndrome，formula making principle，dosage，preparation method，decoction method and medicine taking method of Dihuang Yinzi，in order to provide the ancient literary evidence support for the development and clinical application of classic famous prescriptions. It is found that Dihuang Yinzi was from Xuanming Lunfang written by LIU He-jian，a doctor of Jin dynasty. It was composed of 12 kinds of herbs，namely Rehmanniae Radix Praeparata，Morindae Officinalis Radix，Corni Fructus，Cistanches Herba，Dendrobii Caulis，Aconm Lateralis Radix Praeparaia，Schisandrae Chinensis Fructus，Cinnamomi Ramulus，Poria，maimendong，Acori Calami Rhizoma and Polygalae Radix, and mainly used for the treatment of Yinfei. The later records of Dihuang Yinzi mostly followed the prescription composition and main treatment set forth in Xuanming Lunfang，and its clinical application was expanded. In the 199 articles with the indications for disease treatment，Yinfei was the most commonest indication, and took up about half of the total，which was followed by stroke，taking up about two fifths of the total. It was also used for the treatment of sudden aphonia，flaccidity syndrome，vertigo，enuresis. Dihuang Yinzi has a wide range of treatment，but the pathogenes is always belongs to "the deficiency of water and fire in the kidney". The recipe of Dihuang Yinzi was unique，and can be used to treat both the upper and lower parts of the body，as well as both the outward symptoms and root causes of an illness at the same time， in particular，it mainly focuses on the treatment of the lower and the root. Among the 56 literatures with drug dosage records，about one third of them inherited the records of Xuanming Lunfang: "Equal division，the top is the end，3 qian for each dose." The dosage was generally light. The preparations are mostly decoction and boiled powder. In the decocting and taking methods，it was suggested that "turbid medicine shall be boiled for a short time，and taken after several boilings，with no limit to time."

Anthraquinones,dianthrones and tannins are the main active ingredients of Rheum tanguticum. In this study the three components were determined by HPLC,and the results were analyzed by multiple comparisons,principal components analysis(PCA)and correspondence analysis(CA). The results showed that the contents of components in different growing areas and types(wild and cultivated) reached a significant level(P<0. 05). Baiyu county,Xiaojin county and Ruoergai county had obvious advantages in the accumulation of catechin hydrate,rhien and sensenoside A respectively. The principal component was different in two growing type and the wild environment was conducive to combined anthraquinones accumulation. For active components,normalized planting was better than retail cultivating. Therefore,the effect on the accumulation of chemical components in Rh. tangusticum,should be taken into full account in the selection of the cultural base of Rh. tanguticum. The standardized cultivating is superior to retail cultivating in terms of the accumulation of active ingredients,and standardized planting is inferior to the wild.
Anthraquinones ; analysis ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; Phytochemicals ; analysis ; Plants, Medicinal ; chemistry ; Rheum ; chemistry ; Tannins ; analysis

Objective The aim of this study was to investigate associations of overall obesity (OO) and abdominal obesity (AO) with brachial-ankle pulse wave velocity (baPWV) among type 2 diabetes(T2DM) patients. Methods A community-based study for T2DM patients was conducted in rural communities in Beijing．Every patient completed a questionnaire to collect demography, lifestyle and diseases history, and underwent physical examinations, baPWV assessments and blood biochemical tests. Multivariate linear regression was used to assess the relationship between obesity index and baPWV. Abnormal baPWV was defined as patients with baPWV≥1,700 cm/s. Logistic regression model was performed to explore the risk of abnormal baPWV after adjusting for poetential confounders step by step. Results A total of 2 048 T2DM patients were recruited. The average age was (59.2±8.3) years and total prevalence of abnormal baPWV was 49.7%. After multivariable adjustment, linear regression showed that there was a negative correlation between body mass index(BMI) and baPWV and a positive correlation between waist-to-hip ratio (WHR) and baPWV. Compared to normal weight group, those with BMI≥28 kg/m2 had lower risk of abnormal baPWV (OR=0.59, 95% CI: 0.44-0.78，P<0.001), but there was an increased risk of 46% among patients with obesity in WHR (OR=1.46, 95% CI:1.07-2.00，P=0.018). Compared to those without OO and AO, patients without OO but with AO had a 1.67-fold increasesd risk of abnormal baPWV (OR=1.67, 95% CI: 1.19-2.35，P=0.003). Conclusions Abdominal obesity is related with arterial stiffnening among T2DM patients, and it is critical to evaluate arterial stiffness of T2DM patients with abdmonal obesity and normal BMI in order to reduce future risk of cardiovascular diseases.

Objective: To study the correlation between the content changes of main medicinal ingredients and the color values of Rhei Radix et Rhizoma during storage based on the principle of chromaticity analysis,and to provide reference for studying on the mechanism of discoloration and improving the quality evaluation of Rhei Radix et Rhizoma. Method: Simulated accelerated test was adopted in this study, where Rhei Radix et Rhizoma was stored under high temperature(40±5)℃,high humidity RH(92.5±5)%and strong light(4 000±500)Lx conditions to accelerate its discoloration. For the samples taken at different time points,the color value was determined by spectrophotometer and the total contents of anthraquinone and free anthraquinones,sennoside A,B,catechin and gallic acid were determined by high performance liquid chromatography (HPLC). The correlation between the effective components and the color value of rhubarb was analyzed by SPSS software. Result: During the storage process,it was observed by the eye that the color of Rhei Radix et Rhizoma was significantly darker and darker in the simulated acceleration test. According to the analysis of the chromaticity value results,the changes of chromaticity values L^*and E^*ab of Rhei Radix et Rhizoma were significantly negatively correlated with free strontium content(P<0.05),and significantly positively correlated with catechin content(P<0.05),but there was no correlation with total anthraquinones and sennoside A. The chromaticity value a^* was significantly negatively correlated with gallic acid(P<0.05) and significantly positively correlated with sennoside B(P<0.05). Conclusion: There is a certain correlation between the change of color value and the content of six medicinal ingredients during Rhei Radix et Rhizoma storage.

BackgroundNanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models.

MethodsWe synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group.

ResultsWe demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 10/L at the 28 day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] μmol/L) at the 28 day, particularly those injected with 1.5 mg/kg NaYbF:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney.

ConclusionThe use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.

BACKGROUNDLuminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure.

METHODSAdult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice.

RESULTSTwo different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain.

CONCLUSIONSThis study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.