ObjectiveTo establish a high-performance liquid chromatography（HPLC） for the quantitative analysis of multiple components in Gegen Qinlian tablets， and to comprehensively evaluate the quality of samples from different manufacturers by integrating chemical pattern recognition and technique for order preference by similarity to ideal solution（TOPSIS）， in order to provide a reference basis for quality evaluation and control of Gegen Qinlian tablets. MethodsHPLC was employed to determine the contents of 10 components in 28 batches of Gegen Qinlian tablets collected from 6 manufacturers， and taking the detection results as variables， SIMCA 14.1 and SPSS 26.0 were employed for cluster analysis（CA）， principal component analysis（PCA）， and orthogonal partial least squares-discriminant analysis（OPLS-DA） to identify key components affecting the quality. Then， TOPSIS analysis was employed to rank the quality of Gegen Qinlian tablets from the 6 manufacturers and establish a comprehensive quality evaluation method. ResultsA quantitative method for Gegen Qinlian tablets was established. After methodological validation， the method was found to be stable and reliable， and could be used for the quantitative analysis of this preparation. The contents of 3′-hydroxy puerarin， puerarin， 3′-methoxy puerarin， daidzein， coptisine hydrochloride， epiberberine， jatrorrhizine hydrochloride， berberine hydrochloride， palmatine hydrochloride and baicalin in 28 batches of samples were 3.58-7.35， 24.88-42.32， 4.20-9.36， 4.33-7.60， 2.52-6.44， 0.93-4.10， 0.58-3.05， 10.68-22.92， 0.82-4.82， 11.73-60.16 mg·g^-1， respectively. Among them， puerarin， berberine hydrochloride and baicalin all met the limit requirements for this preparation specified in the 2025 edition of the Pharmacopoeia of the People's Republic of China. CA and PCA clustered the 28 batches of samples into 5 categories， PCA extracted 2 principal components with a cumulative variance contribution rate of 90.588%， and OPLS-DA screened out 4 differential markers with variable importance in the projection（VIP） values>1.0， namely baicalin， 3′-hydroxy puerarin， coptisine hydrochloride and palmatine hydrochloride， which might be the main components affecting the quality of Gegen Qinlian tablets. TOPSIS analysis showed that the comprehensive score of each evaluation index（C_i） values of different manufacturers were different. Among them， the C_i of manufacturer B was ranked higher， indicating potentially superior quality， while the C_i of manufacturer A was ranked lower， suggesting potentially inferior quality. ConclusionThis study establishes a quantitative method for Gegen Qinlian tablets， and the content uniformity of the same manufacturer is good， while there are differences in the contents of active components among different manufacturers. Through the chemical pattern recognition analysis， it is found that the content differences of Gegen Qinlian tablets may be related to baicalin， 3′-hydroxy puerarin， coptisine hydrochloride and palmatine hydrochloride.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with autism spectrum disorder (ASD) in conjunct with congenital heart disease (CHD). METHODS: A child who was hospitalized at the Third People's Hospital of Chengdu on April 13, 2021 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). A GTX genetic analysis system was used to analyze the WES data and screen candidate variants for ASD. Candidate variant was verified by Sanger sequencing and bioinformatics analysis. Real-time fluorescent quantitative PCR (qPCR) was carried out to compare the expression of mRNA of the NSD1 gene between this child and 3 healthy controls and 5 other children with ASD. RESULTS: The patient, an 8-year-old male, has manifested with ASD, mental retardation and CHD. WES analysis revealed that he has harbored a heterozygous c.3385+2T>C variant in the NSD1 gene, which may affect the function of its protein product. Sanger sequencing showed that neither of his parent has carried the same variant. By bioinformatic analysis, the variant has not been recorded in the ESP, 1000 Genomes and ExAC databases. Analysis with Mutation Taster online software indicated it to be disease causing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. By qPCR analysis, the expression level of mRNA of the NSD1 gene in this child and 5 other children with ASD was significantly lower than that of the healthy controls (P < 0.001). CONCLUSION The c.3385+2T>C variant of the NSD1 gene can significantly reduce its expression, which may predispose to ASD. Above finding has enriched the mutational spectrum the NSD1 gene.
Male ; Child ; Humans ; Autism Spectrum Disorder/genetics* ; Heart Defects, Congenital/genetics* ; Computational Biology ; Genomics ; Mutation ; RNA, Messenger/genetics* ; Histone-Lysine N-Methyltransferase/genetics*

Objective:To investigate the clinical value of three-dimensional arterial spin marker imaging(3D-ASL) for evaluating collateral circulation compensatory status in patients with cerebral infarction.Methods:A total of 24 patients with cerebral infarction who were treated at Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Chinese Medicine from September 2017 to January 2019 were examined by 1.5-T high-field MR scanner.The changes of cerebral blood flow(CBF) between the infarcted area and the contralateral normal area were compared when the labeled delay time(PLD)=1.5s and PLD=2.5s, and the patients were divided into the group with strong collateral circulation compensation and the group with weak collateral circulation compensation according to the difference in lesion area measured by 3D-ASL(PLD=1.5s and 2.5s). The changes of national institutes of health stroke scale(NIHSS) score and Bathel index at admission and 15 days after admission were compared.Results:3D-ASL measurement of PLD=1.5s showed that the CBF value in the infarcted area was (33.70±20.83)mL/(100g×min), which was significantly lower than that in the contralateral normal area(PLD=1.5s)[(49.93±13.13)mL/(100g×min)]( t=3.229, P<0.05). When PLD=2.5s, ASL measurement results showed that the CBF value in the infarcted area increased significantly[(58.26±23.50)mL/(100g×min) vs.(33.70±20.83)mL/(100g×min)]( t=3.831, P<0.05), and the CBF value in the contralateral normal area also increased significantly[(68.29±14.03)mL/(100g×min) vs.(49.93±13.13)mL/(100g×min)]( t=4.681, P<0.05). At this time, the CBF value in the infarcted area was still significantly lower than that in the contralateral normal area[(58.26±23.50)mL/(100g×min) vs.(68.29±14.03)mL/(100g×min)]( t=1.795, P<0.05). On the day of admission, the BI index of patients in the weak collateral circulation compensation group(12 cases) was significantly higher than that in the strong collateral circulation compensation group(12 cases)[(90.42±10.50) vs.(67.92±27.57)]( t=2.642, P<0.05), and the NIHSS score was significantly lower than that in the strong collateral circulation compensation group[(1.25±1.01) vs.(3.83±3.62)]( t=2.378, P<0.05). After 15 d of admission, there were no significant differences in BI index and NIHSS score between the two groups(all P>0.05). Conclusion:3D-ASL with different delay time can effectively and intuitively reflect collateral circulation compensation of patients with cerebral infarction, and it has very important reference value for the evaluation of patients' disease and the formulation of clinical treatment plan.

Objective To explore the applicable conditions for using urine plutonium monitoring data to assess personal internal doses,in order to provide references for the occupational health management and the urine plutonium monitoring in nuclear sector.Methods Using some plutonium mixtures from DOE nuclear facilities,as an example,the urine plutonium levels were estimated through simulation calculation at 1 mSv effective dose arising from either acute or chronic inhalation of plutonium compounds,respectively.The results were compared with the typical detection limit of radiochemical separation and α-spectrometry.The feasibility of urine plutonium monitoring for dose assessment of internal radiation exposure was discussed.Results Only for type M plutonium compunds,1 mSv detection limit can be achieved using radiochemical separation and α-spectrometry within 10 d after inhalation.Conclusions Before the monitoring plan of urine plutonium is made,detection limits of monitoring method should be considered.Internal dose could be accessed using workplace air monitoring and working hours when necessary.

Objective:To explore the dose distribution characteristics between RapidArc and five-field intensity modulated radiotherapy(5F-IMRT) plans in the treatment of locally advanced pancreatic carcinoma,and to provide reference for selecting the appropriate radiation technique in clinic.Methods:Ten patients with locally advanced pancreatic carcinoma were selected.The patients were scanned by simulation CT, and the targets and organs at risk were contoured. RapidArc plan and 5F-IMRT plan were designed respectively.The treatment time and the differences of dose distribution in the targets and organs at risk of RapidArc and 5F-IMRT plans were compared.Results:The conformal index (CI) of RapidArc plan was superior than that of 5F-IMRT plan(P=0.01).The homogeneity index (HI) of targets were similar between two plans (P>0.05).RapidArc plan decreased the maximum dose (Dmax) of the spinal cord(P=0.005);RapidArc plan decreased the mean dose(Dmean) of stomach(P=0.019);5F-IMRT plan decreased the V20 of kidney(P=0.043);RapidArc plan decreased the mean dose(Dmean) of small intestine(P=0.011).The small intestine V10 and V20 of RapidArc plan were lower than those of 5F-IMRT plan(P=0.015,P=0.14);the monitor unit (MU) of RapidArc plan was significantly lower than that of 5F-IMRT plan,with a 18% reduction from the MU level of the latter one,and the treatment time was reduced by 70.3%.RapidArc plan had the smaller doses at liver and kidney compared with 5F-IM RT plan.Conclusion:For the patients with locally advanced pancreatic carcinoma,RapidArc plan has higher CI. RapidArc plan shows the advantages in the protection of organs.Compared with 5F-IMRT,RapidArc plan has less treatment time and significantly improves the curative efficiency.In clinic, the RapidArc plan is recommended.

The aim of this study was to evaluate the effects of compound probiotics on milk performance,blood biochemical indexes,rumen fermentation parameters and nutrient digestibility of Holstein dairy cows in middle-and-later lactation.Forty-eight dairy cows with similar milk yield,days in milk and age were randomly divided into 4 groups treated with four different levels of compound probiotics as follows:the control group (0 g/d),group 1 (10 g/d),group 2 (20 g/d) and group 3 (30 g/d).The adaptation period was 7 days,and the total experimental period was 60 days.Results showed that:compared with the control group,supplementation of compound probiotics could improve milk yield and significantly increase the concentration of milk protein,lactose and total solids (P＜0.05);there was no significant effect on blood biochemical indexes (P＞ 0.05);compound probiotics could significantly increase the content of ammonia and microbial protein content (MCP) in the rumen (P＜ 0.05);the apparent nutrient digestibility of crude protein and crude fat of group 2 was significantly higher than other groups (P＜0.05);compared with the control group,the economic benefits of group 1,2,3 increased 2.28,4.80 and 4.09 yuan/d,respectively.In summary,dietary supplementation with 20 g/d of compound probiotics was the most effective method for milk performance,rumen fermentation parameters,nutrients apparent digestibility and economic benefit of Holstein dairy cows.

Ebola virus (EBOV) is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA (-ssRNA) viruses, EBOV possess a nucleocapsid protein (NP) to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex (RNP) together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain (NP(core)) possesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an α-helix of EBOV NP(core) itself, which is highly conserved among filoviridae family. Combined with other biochemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.
Crystallography, X-Ray ; Ebolavirus ; physiology ; Humans ; Nucleoproteins ; chemistry ; genetics ; metabolism ; Protein Structure, Tertiary ; Structure-Activity Relationship ; Virus Assembly ; physiology

Objective To compare the planning quality and acute toxicity between RapidArc and fixed gantry angle dynamic intensity modulated radiotherapy (IMRT) in the postoperative radiotherapy for cervical cancer patients.Methods All 35 patients with cervical cancer who had received postoperative radiotherapy were studied,including 17 patients with RapidArc and 18 patients with IMRT.All plans were prescribed 50 Gy in 25 fractions.The dose-volume histogram data,the conformity index and homogeneity index of the targets,the monitor units (MUs) and delivery time were compared.During the treatment,the incidence of acute intestinal and bladder side effects were also compared.Results Compared to IMRT,the conformity index of RapidArc was better(t =3.13,P ＜ 0.05),but the homogeneity index was slightly worse (t =-4.25,P ＜ 0.05).The V20 and V30 of femoral head planned by RapidArc was significantly lower than that by IMRT (t =2.56,2.34,P ＜ 0.05).The mean MU for RapidArc was reduced by 52.1％ compared with IMRT.The mean treatment time for RapidArc was decreased by 46.8％ compared with IMRT.There was no difference in the incidence of acute intestinal and bladder toxicity between the two groups.Conclusion For patients with cervical cancer who need prophylactic postoperative radiotherapy,both RapidArc and IMRT plan can achieve equal target coverage and organs at risk(OAR) sparing.There is no significant difference in dosimetric parameters and acute toxicity between the two groups.Compared with IMRT,RapidArc plan has fewer MUs and less treatment time and significantly improves the treatment efficiency.

Objective:To evaluate the performance of RapidArc technique on cervical cancer patients with various filling status of the bladder. Methods: Conventional fixed field intensity modulation radiated therapy (IMRT) is used as the benchmark. In 10 fe-males suffering from cervical cancer, two CT scans were performed for treatment planning:one with an empty bladder and the other with filled bladder. The prescribed dose was 50 Gy. The images of that with an evacuated bladder and that with filled bladder were planned in the dual-arc RapidArc and the 7-field IMRT, respectively. The implementor of the plan was the Varian TrueBeam linear ac-celerator. Dose-volume histogram was used to evaluate the data from each plan. Results:When the bladder was filled, IMRT and Rapi-dArc homogeneity were 1.05 and 1.04 (P>0.05), respectively. When the bladder was emptied, the homogeneity was 1.04 for both plans (P>0.05). With or without bladder filling, the conformity index was 0.71 and 0.73 for IMRT and RapidArc (P>0.05), respectively. The effect of V30 and V40 (volume for receiving doses of 30 and 40 Gy) on the intestine and the bladder was more favorable in a full than in an empty bladder. No significant difference between the two plans was observed. IMRT exhibited improved V30 on the rectum and on the bladder. RapidArc was much better in terms of monitor unit (MU) and deliver time. Conclusion:No significant differences in the homogeneity and conformity index between dual-arc RapidArc and 7-field IMRT were observed. Filled bladder is better than empty bladder in intestine and bladder protection in both RapidArc and IMRT. IMRT is better on V30 of the rectum and the bladder, whereas RapidArc improved MU and deliver time.

The p53 signaling pathway works as a potent barrier to tumor progression. Two single nucleotide polymorphisms (SNPs) in the gene loci of p53 pathway, p53 codon 72 Arg72Pro and MDM2 SNP309 (T > G), have been shown to cause perturbation of p53 function, but the effect of the two SNPs on the risk of hepatocellular carcinoma (HCC) remains inconsistent. This study investigated the influence of combined p53 Arg72Pro and MDM2 SNP309 on the risk of developing HCC in patients with chronic hepatitis B virus infection, and evaluated the significance of the two combined SNPs on patient prognosis. In total, 350 HCC patients, 230 non-HCC patients, and 96 healthy controls were genotyped for the p53 Arg72Pro and MDM2 SNP309. The combined p53 Pro/Pro and MDM2 G/G genotype was significantly associated with HCC risk (P = 0.047). Multivariate analysis indicated that combined p53 Pro/Pro and MDM2 G/G genotype was an independent factor affecting recurrence and survival (P < 0.05). Patients with combined p53 Pro/Pro and MDM2 G/G genotypes had a poorer prognosis than other genotypes, P < 0.01 for both disease-free survival (DFS) and overall survival (OS). DFS and OS rates also differed significantly between Barcelona Clinic Liver Cancer (BCLC) stage A patients with combined p53 Pro/Pro and MDM2 G/G and other genotypes (P < 0.05). Thus, the combined p53 Pro/Pro and MDM2 G/G genotype is associated with increased risk of developing HCC and is an independent adverse prognostic indicator in early stage HCC.
Carcinoma, Hepatocellular ; diagnosis ; genetics ; surgery ; virology ; Carrier State ; virology ; Cohort Studies ; Female ; Genetic Predisposition to Disease ; genetics ; Hepatitis B virus ; physiology ; Humans ; Liver Neoplasms ; diagnosis ; genetics ; surgery ; virology ; Male ; Middle Aged ; Neoplasm Staging ; Polymorphism, Single Nucleotide ; Prognosis ; Proto-Oncogene Proteins c-mdm2 ; genetics ; Tumor Suppressor Protein p53 ; genetics