Increasing evidence has revealed that maternal cytomegalovirus (CMV) infection may be associated with neurodevelopmental disorders in offspring.Potential relevance between the placental inflammation and CMV-related autism has been reported by clinical observation.Meanwhile,abnormal expression of Toll-like receptor 2 (TLR2) and TLR4 in placenta of patients with chorioamnionitis was observed in multiple studies.IL-6 and IL-10 are two important maternal inflammatory mediators involved in neurodevelopmental disorders.To investigate whether murine CMV (MCMV) infection causes alterations in placental IL-6/10 and TLR2/4 levels,we analyzed the dynamic changes in gene expression of TLR2/4 and IL-6/10 in placentas following acute MCMV infection.Mouse model of acute MCMV infection during pregnancy was created,and pre-pregnant MCMV infected,lipopolysaccharide (LPS)-treated and uninfected mice were used as controls.At E13.5,E14.5 and E18.5,placentas and fetal brains were harvested and mRNA expression levels of placental TLR2/4 and IL-6/10 were analyzed.The results showed that after acute MCMV infection,the expression levels of placental TLR2/4 and IL-6 were elevated at E13.5,accompanied by obvious placental inflammation and reduction of placenta and fetal brain weights.However,LPS 50 μg/kg could decrease the IL-6 expression at E13.5 and E14.5.This suggests that acute MCMV infection during pregnancy could up-regulate the gene expression of TLR2/4 in placental trophoblasts and activate them to produce more proinflammatory cytokine IL-6.High dose of LPS stimulation (50 tg/kg) during pregnancy can lead to down-regulation of IL-6 levels in the late stage.Imbalance ofIL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.

OBJECTIVETo identify whether Radix Bupleuri (Bupleurum chinense) was fumed with sulfur.

METHODA static headspace GC-MS method was used to detect sulfur in the fumatory Radix Bupleuri, the authentic samples free of sulfur was detected as reference.

RESULTSulfur was detected in six samples from nine samples collected in different locations.

CONCLUSIONThe method can be used to detect sulfur rapidly in the fumatory Radix Bupleuri with sulfur.

Bupleurum ; chemistry ; Drug Contamination ; Gas Chromatography-Mass Spectrometry ; methods ; Hot Temperature ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Sulfur ; analysis ; Technology, Pharmaceutical

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.
Aneuploidy ; Cost-Benefit Analysis ; Female ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies ; Trisomy 18 Syndrome/genetics*

Chronic heart failure is a serious heart disease with dyspnea and limited activity tolerance as the main clinical manifestations. Autophagy is a self-protection mechanism in eukaryotic cells and plays an important role in the development of heart failure. Appropriately increasing the level of autophagy during the compensated stage of heart failure and timely removal of necrotic myocardial organelles and other harmful garbage can inhibit myocardial hypertrophy to a certain extent，alleviate myocardial remodeling，and delay heart failure. The theory of healthy Qi and pathogenic Qi is an important basic theory for explaining the occurrence of diseases，and struggle between healthy Qi and pathogenic Qi exists in the entire onset of chronic heart failure，which may lead to pathogenic Qi invasion and healthy Qi deficiency. The regulatory effect of autophagy on cardiomyocytes is similar to the theory of healthy Qi and pathogenic Qi in traditional Chinese medicine （TCM）. Autophagy is the body's self-regulatory mechanism for healthy Qi and pathogenic Qi in a dose-effect manner，Specifically，autophagy can only protect the body's cells to a certain extent，and healthy Qi can only take effect within a certain range and degree. To protect the body from external pathogenic factors，excessive or insufficient autophagy may destroy the stability of the body's environment. In this regard，we use the theory of healthy Qi and pathogenic Qi as a starting point to clarify the function of autophagy in the development of chronic heart failure from a macro and micro perspective，and propose adjusting the balance of healthy Qi and pathogenic Qi in the body to regulate the autophagy of cardiomyocytes. The principle of prevention and treatment is expected to lay the foundation for modern research on the function of autophagy in the development of chronic heart failure in TCM，find novel therapy for chronic heart failure at different stages，and provide new insights into the diagnosis and treatment of chronic heart failure.

The purpose of the study is to analyze the outcomes of randomized controlled trial(RCT) of Chinese herbal medicine formula(CHMF) in the treatment of vascular cognitive impairment caused by cerebral small vessel disease(CSVD-VCI), and provide suggestions for future studies in this field. Three English databases, four Chinese databases, and two online registration websites of clinical trials were searched with use of the search strategy established in advance. Relevant RCTs published in recent ten years were screened, and necessary information was extracted to assess the risk of bias and analyze the outcomes of these RCTs. As a result, a total of 10 461 articles were retrieved, of which 8 681 were kept after de-duplication, and 41 RCTs were included after screening, with a generally higher risk of bias. The outcomes of included RCTs were classified into 9 categories, namely, clinical symptom outcomes, neuroimaging outcomes, neuroelectrophysiological outcomes, blood biochemical outcomes, hemorheology outcomes, physical signs, syndrome scores of traditional Chinese medicine(TCM), clinical effective rate, and safety outcomes. Among them, the most frequently reported outcomes of included RCTs were blood biochemical outcomes, and clinical symptom outcomes showed the highest reporting rate. Besides, 9 RCTs reported syndrome scores of TCM as the outcomes and illustrated corresponding evaluation criteria. The analysis showed that the application of RCT outcomes in this field had clinical rationality and limitations, and there were also some deficiencies in the trial design level, namely, no distinction between primary and secondary outcomes, insufficient blind methods, not detailed description of outcomes, disunity of evaluation tools, and despised endpoint outcomes. These limitations and deficiencies were negatively affecting the quality of RCTs of CHMF in the treatment of CSVD-VCI. Therefore, we suggest that future researchers should be well prepared in the top-level design stage, and actively construct the core outcome set of this field, so as to improve the quality of clinical trials.
Cerebral Small Vessel Diseases ; Cognitive Dysfunction ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Phytotherapy

Animals ; Anticonvulsants ; pharmacology ; Drug Evaluation, Preclinical ; methods ; GABA-A Receptor Antagonists ; pharmacology ; Motor Activity ; drug effects ; Pentylenetetrazole ; pharmacology ; Valproic Acid ; pharmacology ; Zebrafish

Based on the network target approach and technology, this study proposed for the first time a novel optimization method for Chinese medicine formulae. Moreover, with Qingluo Decoction as an example, a method for the research and development of Chinese medicine, which combines scientific methodology and experience of famous doctors, was developed. Specifically, based on the composition of Qingluo Decoction, this study used the using network target for intelligent and quantitative analysis on drug actions(UNIQ) to predict the medicinals that targeted the key pathways of rheumatoid arthritis(RA) such as angiogenesis. Then, combining the experience of the first national Chinese medical master LI Ji-ren and Aihui famous Chinese medicine doctor LI Yan and Chinese medicine theory, this study developed a novel angiogenesis-targeted prescription modified Qingluo Decoction(MQLD). Afterward, the clinical efficacy and mechanism of MQLD were verified. The results showed that 27 medicinals with significant regulatory effect on angiogenesis-related key signaling pathways were identified by UNIQ, among which 6 were selected by the Chinese medicine physicians to develop the MQLD. Clinical trials demonstrated that the clinical efficacy of MQLD, in terms of either American College of Rheumatology 20% improvement and 50% improvement criteria(ACR20, ACR50) or TCM syndrome evaluation, was better than that of Qingluo Decoction. Experimental study revealed that MQLD can inhibit RA angiogenesis by acting on the vascular endothelial growth factor(VEGF) pathway, nuclear factor κB(NF-κB) pathway, inflammatory cytokine release, and immune cell regulation. Taken together, this study developed a new formula MQLD with improved clinical efficacy, precise applicable clinical settings, and authorized patent through the network target technology, thus providing a new way for the precise development of Chinese medicine and preservation of the experience of famous physicians.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Vascular Endothelial Growth Factor A ; Prescriptions ; Physicians

Objective:To provide a scientific basis for the classification of Phyllanthi Fructus product grades. Method:A total of 30 batches of Phyllanthi Fructus currently available in the market were collected for quantification based on such appearance indexes as diameter， thickness， grain weight， and crust colour （L^*， a^*， and b^* values）. The contents of gallic acid， corilagin， chebulagic acid， and ellagic acid were measured by high performance liquid chromatography （HPLC）， followed by descriptive statistical analysis （DSA）， analysis of variance （ANOVA）， and principal component analysis （PCA） to determine the importance of each main index and explore the correlations between the appearance indexes and internal components. The classification standard of Phyllanthi Fructus product grades was formulated， and its scientificity was verified in hepatocelular carcinoma HepG2 cells. Result:The correlation analysis revealed that the crust colour L^*， a^*， and b^* values were significantly negatively correlated with corilagin， chebulagic acid， and ellagic acid （|r|>0.5， P<0.01）， but irrelevant to gallic acid （|r|<0.1）. Considering the variable coefficient of each index， PCA results， and the requirement of gallic acid as quality indicator for Phyllanthi Fructus in Chinese Pharmacopoeia， the crust colour L^*， a^*， and b^* values and gallic acid content were determined to be the classification indexes. The K-means cluster analysis confirmed that products with crust colour L^*<44， a^*<7， and b^*<10 and gallic acid content >1.6% could be classified into the first class， and those failing to meet the above requirements into the second class. The cell experiment demonstrated that the half-maximal inhibitory concentration （IC₅₀） of the first-class product against hepatocelular carcinoma HepG2 cells was lower than that of the second-class product. A colourimetric card was developed based on crust colour L^*， a^*， and b^* values to provide a visual tool for on-site evaluation of Phyllanthi Fructus products. Conclusion:This study has initially established the classification standard of Phyllanthi Fructus product grades， which contributes to guiding price negotiation of Phyllanthi Fructus products based on quality grade and thus ensuring high quality and high price.