Whole exome sequencing analysis and prenatal diagnosis in children with neurodevelopmental disorders / 中华预防医学杂志

To explore the application value of whole exome sequencing (WES) in the diagnosis of prenatal and postnatal neurodevelopmental disorders (NDDs). A total of 70 patients diagnosed with NDDs who underwent WES at the Medical Genetics Center of the Maternal and Child Health Hospital of Hubei Province between June 2020 and July 2021 were retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples and amniotic fluid. WES-based copy number variant (CNV) analysis was integrated into the routine WES data analysis pipeline. The results showed that a molecular diagnosis rate could be made in 21/70 (30%) cases. Of 21 positive cases, 14 (23%) cases were detected by single-nucleotide variant/small insertion/deletion (SNV/Indel) analysis, of which 12 variants were novel, 6 (9.8%) cases were detected by WES-based CNV analysis, and 1 (1.6%) case was detected by a combination of both. The diagnostic yield of WES combined with CNV analysis was higher than that of SNV/Indel analysis alone (30%, 21/70 vs. 20%, 14/70). Of the 28 prenatally diagnosed cases, 6 cases were found to have inherited parental variation for NDDs, 10 cases were found not to have the same pathogenic variation as the proband, and the remaining 12 cases were found to have no pathogenic or likely pathogenic variation that could explain the NDDs phenotype. Clinical follow-up showed that 5 families opted for abortion and the remaining had no current abnormalities. In conclusion, WES may be an effective method to clarify the genetic etiology and prenatal diagnosis of NDDs, which is helpful in assessing the prognosis to aid clinical management and reproductive guidance.

Clinical and genetic diagnosis for 26 paitents with hereditary spherocytosis / 中南大学学报(医学版)

OBJECTIVES@#Hereditary spherocytosis (HS) is the most common hereditary defect of the red cell membrane, mainly characterized by anemia, jaundice, and splenomegaly. Due to the atypical clinical manifestations and negative family history of some patients, as well as the low sensitivity and specificity of traditional laboratory examinations, it is easy for it to escape diagnosis or be misdiagnosed. At present, it has been confirmed that the mutation of ANK1, SPTB, SPTA1, SLC4A1 and EPB42 genes can cause the deletion of their corresponding coding proteins, and thus lead to the defect of erythrocyte membrane. This study aims to analyze the feasibility and clinical application value of HS gene diagnosis.@*METHODS@#Data of 26 patients from Hunan, China with HS admitted to the Department of Hematology, Second Xiangya Hospital of Central South University from January 2018 to September 2021 were retrospectively collected, and their clinical manifestations and results of laboratory examinations were analyzed. Next-generation sequencing (NGS) combined with Sanger sequencing were applied. The mutation of HS pathogenic gene and the variation of uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1 (UGT1A1), a key enzyme in the regulation of bilirubin metabolism, were detected. The results of pathogenic gene variations were interpreted pathogenic gene variations in accordance with the Standards and guidelines for the interpretation of sequence variants published by the American College of Medical Genetics and Genomics (ACMG). The clinical characteristics of patients with different gene variants were analyzed, and the clinical diagnosis and genetic diagnosis were compared.@*RESULTS@#Among the 26 patients with HS, there were 23 cases of anemia, 25 cases of jaundice, 24 cases of splenomegaly, and 14 cases of cholelithiasis. There were 16 cases with family history and 10 cases without family history. The results of HS mutation test were positive in 25 cases and negative in 1 case. A total of 18 heterozygous mutations of HS pathogenic genes were detected in 19 families, among which 14 were pathogenic, 1 was likely pathogenic and 3 were of unknown significance. SPTB mutations (12) and ANK1 mutations (4) were the most common. The main variation types were nonsense mutation (9). There were no significant differences in peripheral blood cell parameters and hemolysis indicators between the SPTB mutant group and the ANK1 mutant group (all P>0.05). The rate of splenectomy in ANK1 mutation group was higher than that in SPTB mutation group, and the difference was statistically significant (χ2=6.970, P=0.014). There were no significant differences in peripheral blood cell parameters and hemolysis indicators among different mutation types (nonsense mutation, frameshift mutation, splice site mutation and missense mutation) (all P>0.05). Among the 18 clinically confirmedpatients, there were 17 cases whose diagnosis is consistent with the genetic diagnosis. Eight patients were clinically suspected, and all of them were confirmed by detection of HS gene mutation. Twenty-four patients with HS underwent UGT1A1 mutation detection, among which 5 patients carried UGT1A1 mutation resulting in a decrease in enzyme activity, and 19 patients had normal enzyme activity. The level of total bilirubin (TBIL) in the group with reduced enzyme activity was higher than that in the group with normal enzyme activity, and the difference was statistically significant (U=22, P=0.038).@*CONCLUSIONS@#Most patients with HS have anemia, jaundice and splenomegaly, often accompanied by cholelithiasis. SPTB and ANK1 mutations are the most common mutations in HS pathogenic genes among patients in Hunan, China, and there was no significant correlation between genotype and clinical phenotype. Genetic diagnosis is highly consistent with clinical diagnosis. The decrease of UGT1A1 enzyme activity can lead to the aggravation of jaundice in HS patients. Clinical combined gene diagnosis is beneficial for the rapid and precision diagnosis of HS. The detection of UGT1A1 enzyme activity related gene variation plays an important role in evaluation of HS jaundice.

Comparison of the predictive value of anthropometric indicators for the risk of benign prostatic hyperplasia in southern China / 亚洲男科学杂志(英文版)

This study aimed to compare the predictive value of six selected anthropometric indicators for benign prostatic hyperplasia (BPH). Males over 50 years of age who underwent health examinations at the Health Management Center of the Second Xiangya Hospital, Central South University (Changsha, China) from June to December 2020 were enrolled in this study. The characteristic data were collected, including basic anthropometric indices, lipid parameters, six anthropometric indicators, prostate-specific antigen, and total prostate volume. The odds ratios (ORs) with 95% confidence intervals (95% CIs) for all anthropometric parameters and BPH were calculated using binary logistic regression. To assess the diagnostic capability of each indicator for BPH and identify the appropriate cutoff values, receiver operating characteristic (ROC) curves and the related areas under the curves (AUCs) were utilized. All six indicators had diagnostic value for BPH (all P ≤ 0.001). The visceral adiposity index (VAI; AUC: 0.797, 95% CI: 0.759-0.834) had the highest AUC and therefore the highest diagnostic value. This was followed by the cardiometabolic index (CMI; AUC: 0.792, 95% CI: 0.753-0.831), lipid accumulation product (LAP; AUC: 0.766, 95% CI: 0.723-0.809), waist-to-hip ratio (WHR; AUC: 0.660, 95% CI: 0.609-0.712), waist-to-height ratio (WHtR; AUC: 0.639, 95% CI: 0.587-0.691), and body mass index (BMI; AUC: 0.592, 95% CI: 0.540-0.643). The sensitivity of CMI was the highest (92.1%), and WHtR had the highest specificity of 94.1%. CMI consistently showed the highest OR in the binary logistic regression analysis. BMI, WHtR, WHR, VAI, CMI, and LAP all influence the occurrence of BPH in middle-aged and older men (all P ≤ 0.001), and CMI is the best predictor of BPH.

Qualitative Analysis of Metabolites of Aristolochiae Fructus Aqueous Extract in Rats / 中国实验方剂学杂志

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MSE） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg-1·d-1） or AAⅠ（5 mg·kg-1·d-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min-1. Positive ion mode of electrospray ionization（ESI+） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MSE was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.

Expression and prognostic significance of cell division cycle associated protein 5 in pancreatic cancer tissues / 肿瘤研究与临床

Objective:To analyze the expression of cell division cycle associated protein 5 (CDCA5) in pancreatic cancer tissues and its correlation with prognosis based on the bioinformatics.Methods:The RNA sequencing data (HTSeq-FPKM) and corresponding clinical information of 168 pancreatic cancer samples from January to December 2021 were downloaded from the Cancer Genome Atlas (TCGA) database, and the data of 179 pancreatic patients from January to December 2021 were downloaded from the GEPIA2 database, and 171 normal pancreatic tissues from TCGA and GTEx databases were simultaneously integrated. The relative expression level of CDCA5 mRNA in pancreatic cancer patients in GEPIA2 database and its relationship with overall survival (OS) and disease-free survival (DFS) were explored. Combined with the clinical data of the patients, univariate and multivariate Cox regression model analysis was used to analyze the factors influencing the OS of pancreatic cancer patients. Gene set enrichment analysis (GSEA) was performed to investigate the possibly involved signal pathways of CDCA5 in pancreatic cancer.Results:In the GEPIA2 database, the relative expression level of CDCA5 mRNA in pancreatic cancer tissues was higher than that in normal pancreatic tissues, and the difference was statistically significant ( P < 0.05). The pancreatic cancer patients were divided into the high CDCA5 mRNA expression group (89 cases) and the low CDCA5 mRNA expression group (89 cases) according to the median of relative expression level of CDCA5 mRNA (the case equal to the median value was not subgrouped). Survival analysis showed that patients with high CDCA5 mRNA expression had shorter OS ( P = 0.024) and DFS ( P = 0.025) compared with those with low CDCA5 mRNA expression. Multivariate Cox analysis showed that in TCGA database, N staging ( HR = 2.15, 95% CI 1.24-3.72, P = 0.006) and CDCA5 expression ( HR = 1.71, 95% CI 1.23-2.38, P = 0.001) were independent influencing factors of OS for pancreatic cancer patients. The results of GSEA enrichment analysis indicated that high CDCA5 mRNA expression was enriched in 13 biological pathways [all P < 0.05, false discovery rate (FDR) < 0.005] including cell cycle, DNA replication, homologous recombination, pyrimidine metabolism, mismatch repair, pentose phosphate pathway, glycolysis gluconeogenesis and p53. The expression of CDCA5 mRNA was positively correlated with the expressions of HK2, PKM, PGK1, ALDOA, EN01 and LDHA (all P < 0.05). Conclusions:CDCA5 is highly expressed in pancreatic cancer tissues and is associated with poor prognosis of patients, and it can be used as a prognostic marker for pancreatic cancer.

Advances on the toxicology and molecular mechanisms of different components of ambient fine particulate matter / 中华预防医学杂志

Ambient fine particulate matters (PM2.5) refer to particulate matters with an aerodynamic diameter less than or equal to 2.5 μm. PM2.5 enter the body through the target organ-lung, and can induce a variety of adverse health effects (such as cardiovascular diseases, diabetes, respiratory diseases, neurodegenerative diseases and adverse birth outcomes). PM2.5 are known to have complex compositions (including water-soluble/-insoluble components and biological components), diverse sources and capacity of secondary transformation. Numerous epidemiological and toxicological studies indicated that different components of PM2.5 may induce adverse health effects through different biological mechanisms. In adddition, co-exposure of different components and their interaction should also be considered. Thus here we have systematically reviewed studies in recent years about the toxicological effects and underlying mechanisms of different components of ambient fine particulate matters, including inflammatory response, oxidative stress, endoplasmic reticulum stress, activation of the NF-κB signaling pathway and so on. The information may give some insights into the prevention and treatment of adverse health effects caused by exposure to different components of PM2.5.

Correlations between physical activity, sedentary behavior and physical posture disorders in primary school students / 中国学校卫生

Objective@#To explore correlations between physical activity (PA), sedentary behavior (SB) and physical posture disorders in primary school students, and to provide reference for the prevention and correction of adverse body posture in this group.@*Methods@#From September to December 2020, 206 children from 4 primary schools in Chaoyang District of Beijing were selected by multistage stratified cluster random sampling method. Body posture and PA were assessed using a body posture tester and a triaxial accelerometer. Children s Leisure Activity Questionnaire was used to investigate SB.@*Results@#The detection rate of abnormal body posture in primary school students was 76.70%. PA showed positive assocation with high and low shoulder, X/O leg, pelvis forward, spine curvature and comprehensive evaluation ( β =0.17, 0.21, 0.19, 0.24, 0.19, P <0.05). SB had significant negative linear correlation with high and low shoulder, X/O leg,pelvis forward, spine curvature and comprehensive evaluation ( β = -0.24 , -0.22, -0.36, -0.24, -0.27, P <0.05). In the combination analysis, children with high PA plus low SB ( OR=2.12, 95%CI= 1.46-3.37, P <0.05) and children with low PA plus high SB had the highest and lowest advantages of qualified rate of body posture assessment,respectively. Compare with low SB and low PA( OR=1.71, 95%CI=1.41-2.74, P <0.05), high PA and high SB ( OR=1.85, 95%CI=1.38-2.86, P <0.05) had higher qualified rate of body posture assessment.@*Conclusion@#Physical activity shows positive effects on physical posture while sedentary behavior shows negative effects on physical posture. The combination of PA and SB has a counteracting or synergistic interaction effect.

Study on synergistic effect of Qingkailing Injection and Shengmai Injection on organ injury in endotoxemia rats / 中国中药杂志

As a dangerous disease with rapid progression, endotoxemia is easy to induce the damage to multiple organs. However, its specific and efficient treatment methods are still lacking at present. Both Qingkailing Injection(QKLI) and Shengmai Injection(SMI) have been proved effective in anti-inflammation, anti-endotoxin and organ protection. In this study, carrageenan and endotoxin were injected successively into rats to establish an endotoxemia model. Different doses of QKLI and SMI were administered to the endotoxemia rats by intraperitoneal injection separately or in combination. Then the count of white blood cells, the number of platelets, the content of cytokines, biochemical indexes, organ coefficient and pathological changes of main organs in the rats were detected. The results showed that the rats in the model group had obvious symptoms of endotoxemia, i.e., leucopenia, thrombocytopenia, increase in cytokines(IL-6 and TNF-α) and biochemical indexes of liver and kidney function as well as pathological damage to liver, kidney and lung. QKLI alone can alleviate the above symptoms of endotoxemia and the organ injury. SMI alone is less effective in improving disseminated intravascular coagulation(DIC) and cytokine secretion complicated with endotoxemia, but capable of reducing the inflammation degree of the lung, liver and kidney. The combination of QKLI and SMI remarkably increased the number of platelets in the peripheral blood, improved the liver and kidney function and reduced inflammatory factors, with lung, liver, kidney and other organ structures protected well. Moreover, the improvement effect of the combination of QKLI and SMI was stronger than those of the two injections alone at fixed doses, indicative of a synergistic effect.

Research progress on in vitro models of cardiomyocyte injury / 中国中药杂志

Cardiovascular diseases seriously endanger human health and life. The accompanying myocardial injury has been a focus of attention in society. Chinese medicine,serving as a natural and precious reservoir for the research and development of new drugs,is advantageous in resisting myocardial injury due to its multi-component,multi-pathway,and multi-target characteristics. In recent years,with the extensive application of culture method for isolated cardiomyocytes,a cost-effective,controllable in vitro model of cardiomyocyte injury with uniform samples is becoming a key tool for mechanism research on cardiomyocyte injury and drug development.A good in vitro model can reduce experimental and manpower cost,and also accurately stimulate clinical changes to reveal the mechanism. Therefore,the selection and establishment of in vitro model are crucial for the in-depth research. This study summarized the modeling principles,evaluation indicators,and application of more than ten models reflecting different clinical conditions,such as injuries induced by hypoxia-reoxygenation,hypertrophy,oxidative stress,inflammation,internal environmental disturbance,and toxicity. Furthermore,we analyzed advantages and technical difficulties,aiming to provide a reference for in-depth research on myocardial injury mechanism and drug development.

Evaluation of Lateral Pterygoid Muscle Contraction in Patients with Temporomandibular Disorders Based on 3D-T2 Weighted Imaging / 中国医学科学院学报

Objective To evaluate lateral pterygoid muscle(LPM)contraction in the patients with temporomandibular disorders(TMD)based on 3D-T2 weighted imaging(3D-T2WI).Multiplanar reconstruction(MPR)was employed to measure the length of LPM in the images taken in closed-and open-mouth positions. Methods Seventeen TMD patients [age of(29.82±10.70)years,males/females=8/9] and 13 normal volunteers [control,age of(23.54±3.31)years,males/females=6/7] received 3D-T2WI of the temporomandibular joints in closed-and open-mouth positions from November 2019 to April 2020 in Department of Radiology,Hainan Hospital of Chinese PLA General Hospital.According to the position of the discs,the subjects were classified into the following groups:TMD with disc displacement without reduction(TMD-DDwoR),TMD with disc displacement with reduction(TMD-DDwR),TMD without disc displacement(TMDwoDD),and normal control without disc displacement(NCwoDD).MPR was employed to measure the maximal length of the superior belly of LPM.One-way analysis of variance,receiver operating characteristic curve,and permutation test were employed for the statistical analyses. Results The contraction of LPM was significantly shorter in TMD-DDwoR group [(3.36±1.96)mm] than in TMDwoDD group [(7.90±3.95)mm],NCwoDD group [(8.77±3.13)mm](

Research progress on adverse reactions and pseudo-allergic reactions of traditional Chinese medicine injections / 中国中药杂志

Since the safety re-evaluation of traditional Chinese medicine(TCM) injections began in 2009, some TCM injection companies and research institutes have done a lot of work. And with the increase of drug development and drug production technology levels in China, the safety of some TCM injections has been greatly improved. There are safety risks in TCM injections, which are mainly reflected in unclear basis of medicinal materials, simple production process, poor controllability of quality standards, nonstan-dard drug instructions and irrational medication in the use process. This paper describes the research progress of the above-mentioned aspects of TCM injections. In addition, the author team found that adverse reactions of TCM injections are mainly pseudo-allergic reactions. Therefore, a lot of work has been done in detection of pseudo-allergic reactions, mechanism research and risk control. This part of the work is also described in this article.

Pseudoallergic Reactions of Xuebijing Injection and Its Rational Drug Use / 中国实验方剂学杂志

Objective:To investigate whether the adverse reactions of Xuebijing injection (XBJJ) are mainly pseudoallergic reactions and explore the influencing factors of its pseudoallergic reactions. Method:Mouse model of pseudoallergic reaction was used to study the anaphylactoid reaction of XBJJ which at 0.5, 1 and 2 times of the highest clinical concentration. Next, we compared the differences in pseudoallergic reactions caused by XBJJ for different storage times after preparation. Specifically, XBJJ was prepared into different concentrations, stored for 10 minutes, 2.5 hours, 6 hours and 24 hours, and then injected into the tail vein of mice. Finally, three different injection speeds of 3 seconds, 45 seconds and 90 seconds were selected for XBJJ injection, and then the differences in the paeudoallergic reactions induced by XBJJ in mice under different injection speeds were compared. Result:XBJJ induces pseudoallergic reactions in mice when the drug concentration is higher than the clinically recommended concentration. Compared with storage for 10 minutes after preparation, the degree of pseudoallergic reaction in mice induced by the same concentration of XBJJ increased with the extension of storage time. In addition, when XBJJ was injected in 3 s (the injection rate was 0.083 mL·s^-1), it produced the strongest pseudoallergic reaction. Conclusion:The adverse reactions induced by XBJJ are mainly pseudoallergic reactions. Excessive storage time after preparation and fast injection speed of XBJJ will lead to aggravation of pseudoallergic reactions in mice. When XBJJ is used clinically, it should strictly follow the usage, dosage, concentration, and drip rate recommended in the drug instruction manual. Rational drug use is of positive significance for improving the safety of XBJJ.

Adequate Animal Models of Hyperuricemia for Traditional Chinese Medicine Screening / 中国实验方剂学杂志

Objective:To compare the characteristics of four commonly adopted animal models of hyperuricemia （HUA） for traditional Chinese medicine （TCM） screening， so as to choose the adequate model for screening Chinese herbs and herbal compounds capable of lowering the uric acid. Method:Fifty-four male SD rats were randomly divided into nine groups， namely the normal group， hypoxanthine （HX） + oxonic acid potassium salt （OAPS） model group， yeast extract （YE） + OAPS model group， low-dose adenine （AD） + ethambutol （EMB） model group， high-dose AD + EMB model group， and four positive drug allopurinol （Allo） groups. The modeling lasted for 14 d. The levels of serum uric acid （SUA）， urinary uric acid （UUA）， serum creatinine （SCr）， urea nitrogen （BUN）， kidney injury molecule 1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL） were detected on the 3rd， 7th， and 14th days. Urine was collected on the 7th and 14th days to investigate changes in urine volume， and the crystals in the residual urine were observed under a polarizing microscope. After the modeling， the kidney was harvested and weighed， followed by pathological examination. Result:The urine volumes in the HX + OAPS model group and high-dose AD + EMB model group were significantly reduced （<italic>P</italic><0.05）. The renal indexes of each model group， except for the YE + OAPS model group， were significantly elevated （<italic>P</italic><0.05， <italic>P</italic><0.01）. The increase in SUA of the HX + OAPS model group and YE + OAPS model group started later （<italic>P</italic><0.05）. The KIM-1 and NGAL levels of the HX + OAPS model group rose significantly from the 7th day （<italic>P</italic><0.05， <italic>P</italic><0.01）， and the BUN increased significantly on the 14th day （<italic>P</italic><0.05）. There was no significant difference in the above-mentioned indicators in the YE + OAPS model group. The SUA levels of the low- and high-dose AD + EMB model groups increased significantly on the 3rd day （<italic>P</italic><0.05， <italic>P</italic><0.01）， with a persistent increase found in the low-dose AD + EMB model group. Besides， the increase in BUN， KIM-1， and NGAL occurred later （<italic>P</italic><0.05， <italic>P</italic><0.01）. By contrast， the high-dose AD + EMB model group exhibited a transient increase in SUA. Moreover， the SCr， BUN， KIM-1， and NGAL elevation occurred earlier and were more obvious than those in the low-dose AD + EMB model group （<italic>P</italic><0.01）. Remarkable histomorphological abnormalities were detected in the kidney of all model groups， except for the YE+OAPS model group， with the most severe injury present in the high-dose AD+EMB model group. Conclusion:The four models commonly used to screen TCM have their own characteristics. In the four models， the SUA elevation in the HX + OAPS model group and YE + OAPS model group started later， with the mild renal injury observed in the HX + OAPS model group instead of the YE + OAPS model group. The SUA of the low-dose AD + EMB model group increased rapidly and lasted for a long time， accompanied by mild renal injury. The SUA of the high-dose AD + EMB model group only showed a transient increase， accompanied by severe renal injury. The investigation on the characteristics and application of different models and the evaluation of these models based on sensitive and objective indicators are helpful for determining the suitable model for the screening of TCM targeting HUA in the future.

Synergistic Effect of Xiangdan Injection and Qingkailing Injection on Organ Injury Caused by Acute Inflammation and Thrombosis in Rats / 中国实验方剂学杂志

Objective:To investigate the synergistic effect of Xiangdan injection （XDI） and Qingkailing injection （QKLI） in the treatment of inflammation and thrombosis animal model based on changes of thrombus， inflammatory indexes， organ function， and pathological changes. Method:A total of 100 male SD rats were randomly divided into a normal control group， a model group， XDI groups （2.5， 5 mL·kg^-1）， QKLI groups （5， 10 mL·kg^-1）， and XDI + QKLI groups ［（2.5+5） mL·kg^-1，（2.5+10） mL·kg^-1，（5+5） mL·kg^-1，and （5+10） mL·kg^-1］ according to the body weight， with 10 rats in each group. Rats were treated correspondingly by intraperitoneal injection once a day for 4 days. The normal control group and the model group received normal saline. On the second day of administration， the model was induced in rats except those in the normal control group. Specifically， 25 mg·kg^-1carrageenan was injected intraperitoneally into the rats， followed by an injection of 50 μg·kg^-1 lipopolysaccharide （LPS） through the tail vein 16 hours later. Twenty-four hours after LPS injection， the rats were detected for liver index， kidney index， the number of platelets （PLT）， thrombus length， and biochemical indicators such as aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， creatinine， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was used to determine the content of inflammatory factors interleukin-6 （IL-6） and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of heart， liver， lung， and kidney， as well as the grading of organ injury. Result:Compared with the normal group， the model group showed decreased PLT， lengthened thrombus in the tail， increased liver index， elevated content of ALT， ALP， BUN， IL-6， and TNF-<italic>α</italic> （<italic>P</italic><0.05， <italic>P</italic><0.01）， and damaged liver， lung， and kidney tissues （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the conditions in the model group， XDI at 5 mL·kg^-1 reduced serum ALT and ALP in rats （<italic>P</italic><0.05， <italic>P</italic><0.01）， QKLI at 5 and 10 mL·kg^-1reduced serum levels ALT and ALP， and TNF-<italic>α </italic>content<italic> </italic>（<italic>P</italic><0.05， <italic>P</italic><0.01）. XDI at 5 mL·kg^-1 or QKLI at 10 mL·kg^-1 relieved the LPS-induced lung injury （<italic>P</italic><0.05）， the combination of XDI and QKLI decreased the levels of ALT， AST， ALP， and TNF-<italic>α， </italic>and the effect was predominant in the combination of XDI and QKLI at 5 and 10 mL·kg^-1（<italic>P</italic><0.05， <italic>P</italic><0.01）. Additionally， the length of the tail thrombus was significantly shortened （<italic>P</italic><0.05）， and the degree of lung injury was also reduced （<italic>P</italic><0.05）. The serum levels of ALT and BUN， TNF-<italic>α</italic> content， and liver index of rats were reduced after the combination of XDI and QKLI as compared with those in the single drug groups at the same dose （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:XDI or QKLI can improve or inhibit organ function， organ injury， and inflammatory response in the rat model of inflammation and thrombosis. The combination of the two drugs shows a synergistic effect in reducing the length of venous thrombus， improving liver and kidney function， inhibiting inflammatory factors， and protecting lung， liver， kidney， and other organs.

Study on the action mechanism of Wuling Powder on treating osteoporosis based on network pharmacology / 中国天然药物

Osteoporosis is a health problem to cause global concern. A lot of methods have been used to prevent and treat osteoporosis, but there is still a lack of effective treatment for osteoporosis owing to limited understanding of its mechanism. Therefore, the aim of this present study is to explore the underlying mechanism of Wuling Powder, a traditional Chinese medicine on treating osteoporosis. In this study, we firstly screened and identified the common targets between Wuling Powder and osteoporosis through the related databases, and then explored the relationships among these targets, Wuling Powder and osteoporosis by using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and network analyses. Subsequently, the molecular docking was performed by using systemsDock to evaluate the potential binding relationships between the active components of Wuling Powder and their related targets. The results showed that in total of 14 common targets including CREBBP, ADAM17, GOT1, GAPDH, USP8, ERBB2, EEF1A1, MTOR, RAC1, ETS1, DDX58, GCK, EGF and S100A8 were screened. EGF, ERBB2, MTOR and HIF-1 were the potential therapeutic targets for osteoporosis, and they were also the related targets for predicting active components in Wuling Powder. Taken together, we concluded that Wuling Powder might be used to treat osteoporosis through above these targets.

Histone deacetylase 3 promotes innate antiviral immunity through deacetylation of TBK1

TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.

Feasibility of high concentrated contrast media combined with monochromatic images to improve image quality with double low scanning in dual-layer spectral coronary CT angiography / 中华放射学杂志

Objective:To evaluate the feasibility of high concentrated contrast media combined with monochromatic images to improve image quality with double low scanning in dual-layer spectral coronary CT angiography.Methods:Fifty-six patients with suspected coronary artery disease were enrolled and randomly separated into two groups. All patients were scanned at 120 kVp in step-and-shoot mode using a dual-layer detector CT (IQon spectral CT). Patients were either injected with 18 ml high concentration contrast medium(400 mgl/ml) at 2 ml/s (group A) or 45 ml contrast medium (370 mgl/ml) at 4 ml/s (group B). Forty to 80 keV monoenergetic images with 10 keV increment and conventional image (group A2) were reconstructed for group A, conventional poly-energetic image was reconstructed for group B. Region of interest was placed on aorta root (AO), middle segment of left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) to measure the attenuation and noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Image quality was assessed by two reviewers independently with a 4-point scale on image quality (1-undiagnostic,4-excellent). The objective and subjective image evaluation were compared using the Kruskal-Wallis test. The Steel Dwass was used for multiple comparisons between monoenergetic images in Group A and conventional images in Group B, after the Kruskal-Wallis test.Results:There were significant differences among the attenuation, noise, SNR and CNR of group B, group A2, and monoenergetic images(all P<0.001).The CT value in the aortic root was significantly higher at 40-50 keV monoenergetic images than that in group B(all P<0.05), and similarly, the CT value in LAD,LCX and RCA at 40 keV were superior than that in group B(all P<0.001). There was no significant difference in the noise of the aortic root among 40 keV image, group A2 and group B(all P>0.05),while the noise in the 50-80 keV monoenergetic images were significantly lower than that in Group B(all P<0.001). The SNR and CNR in the aortic root were significantly higher at 40-60 keV monoenergetic images than that in group B(all P<0.001).The SNR in LAD and RCA at 40，50 keV and the CNR in LAD and RCA at 40-60 keV were higher than that in group B(all P<0.01).The SNR at 40-60 keV and CNR at 40-70 keV in LCX were superior than that in group B(all P<0.05). There were significant differences among the subjective image quality score of group B, group A2, and monoenergetic images(all P<0.001).The subjective image quality score of 40，50 keV images were not significantly different from that in group B (all P>0.05),while the score in 60-80 keV image and group A2 were lower than that of Group B(all P<0.001). Conclusion:40，50 keV low monochromatic images derived from dual-layer spectral detect CT combined with high concentrated contrast media can provide comparable or superior image quality with double low scanning in CCTA study.

Efficacy and mechanism of fire needling bloodletting for lower extremity varicose veins / 中国针灸

OBJECTIVE@#To compare the clinical effect of lower extremity varicose veins between fire needling bloodletting and operation, and to explore the possible mechanism.@*METHODS@#A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. In the control group，the operation was adopted. The fire needling bloodletting was applied in the observation group, twice a week for 4 weeks. Before and after treatment, the venous clinical severity score (VCSS) and venous disability score (VDS) were recorded, the hemorheological indexes [blood viscosity, plasma viscosity, hematocrit, fibrinogen and erythrocyte sedimentation rate (ESR)], immune inflammatory response indexes[serum C-reactive protein (CRP), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6)], vascular endothelial cell function indexes [the number of circulatingendothelial cell (CEC), plasma endothelin (ET-1) and NO)] and apoptosis indexes (Bcl-2, Bax and Caspase-3) were detected in the two groups.@*RESULTS@#Compared before treatment, the scores of VCSS and VDS, hemorheological indexes, immune inflammatory response indexes and levels of plasma NO after treatment were reduced in the two groups (<0.05). The level of serum Bax after treatment was reduced in the observation group (<0.05). The number of CEC and levels of plasma ET-1 after treatment were increased in the two groups (<0.05). The levels of serum Bcl-2 and Caspase-3 after treatment were increased in the observation group (<0.05). In the observation group, the scores of VCSS and VDS, hemorheological indexes，immune inflammatory response indexes, vascular endothelial cell function indexes and level of serum Bax after treatment were lower than the control group (<0.05), and the levels of Bcl-2 and Caspase-3 were higher than the control group (<0.05).@*CONCLUSION@#Fire needling bloodletting could effectively treat lower extremity varicose veins, and the mechanism may be related to the improvement of hemorheology, downregulation of immune inflammatory response, improvement of vascular endothelial cell function and inhibition of apoptosis.

Animal model analysis of knee osteoarthritis based on clinical characteristics of Chinese and Western medicine / 中国中药杂志

Knee osteoarthritis(KOA) is a common orthopedic disease. Its main symptoms include pain in the medial knee, aggravated knee pain during walking, limited movement, and joint deformity, which seriously affect the daily life of patients. The replication of animal models consistent with clinical symptoms is the premise of KOA-related experimental research. Based on the clinical characteristics of KOA and Western medicine, this paper discusses the existing KOA animal model, and analyzes the clinical anastomosis of the existing model based on the clinical diagnostic criteria of KOA. Through analysis and comparison, it can be seen that most of the existing modeling methods are single-factor animal models, which have a certain gap with the characteristics of KOA caused by clinical multi-factors and interaction. Moreover, modeling methods are mostly guided by Western medicine, and traditional Chinese medicine pathogenic factors are absent in the modeling process. Only cold stimulation method takes cold and wet into account. In the evaluation of the model, knee swelling, pain and articular rickets were the main evaluation criteria, which were different from the diagnostic criteria of Chinese and Western medicine in KOA. In terms of syndrome differentiation and classification, KOA is divided into kidney vacuity and deficiency of marrow, Yang vacuity and cold coagulation, and blood stasis and arrest in traditional Chinese medicine. The exis-ting animal models often confuse KOA with each other. Only cold stimulation method is used to establish KOA of Yang vacuity and cold coagulation. Therefore, in this paper, based on KOA clinical symptoms between Chinese and Western medicine features, analysis of the existing animal models, for further improving KOA animal models, the standardization of the model to evaluate suggestions, in order to improve the animal models and clinical inosculation between Chinese and Western medicine, the KOA animal model to better serve the scientific research work, promote the related mechanism, pathological changes and drug screening.

Pathogenesis and Traditional Chinese Medicine Regulation of Chloasma / 中国实验方剂学杂志

The pathogenesis of chloasma is complex and diverse. Traditional Chinese medicine （TCM） believes that it is mostly related to liver, spleen and kidney, with hematogenous impassability as the standard and pigmentation on the face or body surface as the main symptom. Western medicine believes that it is closely related to family inheritance, ethnic differences and ultraviolet radiation. At present, there are various clinical therapies, mainly including prevention of ultraviolet radiation, local whitening agent and chemical skin. In addition, TCM plays an important role in the treatment of chloasma, often involving internal use, topical use, acupuncture and moxibustion. Modern studies have shown that TCM therapies mainly regulate the metabolism of antioxidant, endocrine and melanin in vivo. Although the mechanism of action could not explained to some extent, there are still some restriction in the discussions on the mechanism of external use of TCM in controlling chloasma. As the skin nerve-endocrine-immune (NEI) network is proposed and further studied, the role of NEI network in realizing overall functional regulation with cytokines, hormones and neurotransmitters as information molecules has been widely verified and recognized. This paper symmetrically reviewed the pathogenesis of chloasma and the progress of the regulatory effect of TCM, and proposed the possible local efficacy of TCM for external use in treating chloasma by regulating surface NEI network. This is worth further study and exploration in the expectation of providing new ideas for the treatment of chloasma and the studies on the mechanisms of action of TCM for external use.