Analysis of the long-term prognosis of patients with cervical and upper thoracic esophageal cancer treated with simultaneous integrated boost intensity-modulated radical radiotherapy / 中华放射医学与防护杂志

Objective:To evaluate the effects of simultaneous integrated boost intensity-modulated radical radiotherapy (SIB-IMRT) on the long-term prognosis of patients with cervical and upper thoracic esophageal cancer.Methods:From January 2011 to December 2014, a retrospective analysis was performed in 172 patients with cervical and upper thoracic esophageal cancer who were eligible for IMRT. First, the prognosis of all the patients was evaluated using single factor and multivariate analyses. According to the different irradiation method of the patients, the patients were divided into two groups, one of which received conventional IMRT (C-IMRT) and the other of which received SIB-IMRT. Propensity score matching (PSM) analysis was applied to match the two groups of patients and to determine the treatment efficacy of patients after PSM, prognostic factors, failure modes, and side effects. SPSS19.0 statistical software was used to conduct statistical analysis.Results:The median overall survival (OS) and progression-free survival (PFS) times of all the patients were 30 months and 20 months, respectively. The fact whether the surrounding tissues and organs of esophageal lesions were invaded, clinical node staging (cN staging), chemotherapy, and GTV-maximum transverse diameter were observed to be independent influencing factors of OS and PFS in all the patients ( P<0.001, P=0.013, 0.005, 0.002; P<0.001, P=0.017, 0.034, 0.002). In addition, the independent influencing factors of PFS showed short-term efficacy ( P=0.036). After PSM, there were 54 patients in each of the two groups. The result of multivariate analysis showed that the fact whether the surrounding tissues and organs of esophageal lesions were invaded, cN staging, cTNM staging, prescribed dose, GTV-maximum transverse diameter, and irradiation method were independent factors affecting the OS ( P<0.001, P=0.008, 0.014, 0.021, 0.010, 0.008). Similarly, the fact whether the surrounding tissues and organs of esophageal lesions were invaded, cN staging, and GTV-maximum transverse diameter were observed to be independent factors that affect the PFS of patients ( P<0.001, P=0.044, 0.013). The difference in the total failure rate (70.4% vs. 50.0%) and the local regional recurrence rate (61.1% vs. 31.5%) between the C-IMRT and SIB-IMRT groups after treatment was significant ( χ2=4.68, 9.53, P=0.031, 0.002). The incidence of radiation pneumonitis of grade ≥ 1 in the C-IMRT group was significantly higher than that of the SIB-IMRT group ( χ2=6.16, P=0.046), whereas the leukocyte suppression of grade ≥ 2 in the C-IMRT group was significantly lower than that in the SIB-IMRT group ( χ2=12.77, P=0.005). Conclusions:As shown by the result of this study, compared with C-IMRT, SIB-IMRT can improve the OS of patients with cervical and upper thoracic esophageal cancer to a certain extent. Whether SIB-IMRT can improve the PFS of patients requires further research.

Clinical characteristics and prognosis of pregnancy complicated with pheochromocytoma/paraganglioma / 中国综合临床

Pheochromocytoma/paraganglioma is an adrenal tumor that secrets catecholamines and is extremely rare in pregnant women. Its clinical presentation is lack of specificity, and the combination of low prevalence and nonspecific clinical presentation makes diagnosis and treatment difficult. In this study, the clinical data and prognosis of 5 pregnant patients with pheochromocytoma/paraganglioma were analyzed. It was found that hypertension first occurred in 4 patients during pregnancy, and the clinical manifestations of each case were different. Surgical treatment is the first choice in the treatment, patients who cannot operate can choose radionuclide therapy, chemotherapy and targeted therapy. Through follow-up, they all showed recurrence and metastasis at different times. Among them, the patients who continued to be pregnant to the middle and late stages of surgical treatment progressed rapidly, and there were multiple bone metastases throughout the body in a short period of time, and two cases died in a short period of time. Therefore, effective diagnosis, individualized treatment and lifelong follow-up are particularly important.

Progress in the design and quality control of placeboes for clinical trials of traditional Chinese medicine / 中西医结合学报

In recent years, new preparations of traditional Chinese medicines (TCMs) have been developed, increasing the need for their clinical trials. Using placeboes rather than control drugs is increasingly popular in clinical trials of TCMs, as the therapeutic effects of the tested TCMs can be more properly judged. The basic attributes of TCM placeboes include similarity, safety, applicability and controllability. In particular, it is necessary to have similarities in appearance, color, smell and taste between the tested TCMs and placeboes. This is quite difficult for some TCMs due to their distinctive smell and taste. On the other hand, according to the TCM theory on homology of medicine and food, many foods also have certain bioactivities, potentially further complicating the selection of materials for TCM placeboes. In this review, firstly, studies on the special smell and taste of TCMs were introduced. Then, the preparation quality evaluation processes for TCM placeboes were summarized and discussed, based on the relevant literature published in recent years and the research results from our own lab. This review will facilitate the further research and development of TCM placeboes.

Treatment of finger spasm after stroke with wheat grain moxibustion at Shixuan (EX-UE 11) combined with rehabilitation training: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of wheat grain moxibustion combined with rehabilitation training and simple rehabilitation training on finger spasm after stroke.@*METHODS@#A total of 80 patients with finger spasm after stroke were randomly divided into an observation group and a control group, 40 cases in each group. The control group was given routine rehabilitation training, once a day, 30 min each time. The observation group was given wheat grain moxibustion at Shixuan (EX-UE 11) on the basis of the control group, 8~10 moxibustion cones at each point, once a day. Both groups were treated for 6 days as one course of treatment for 4 courses. The motor function of the affected hand (Fugl-Meyer assessment [FMA] score) and muscle tension (modified Ashworth scale [MAS] grading), surface EMG indexes (wrist dorsiflexor muscle and flexor carpal metacarpal muscle mean square [RMS] value), hand muscle strength (neurological deficit score [NDS]) and daily living ability (modified Barthel index [MBI] score) were compared between the two groups before and after treatment, and clinical efficacy was evaluated.@*RESULTS@#After treatment, FMA and MBI scores in the 2 groups were increased compared with before treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The RMS value of wrist dorsiflexor muscle and flexor carpal metacarpal muscle in relaxation and passive function testsand and NDS in the 2 groups were lower than those before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). MAS grading in the 2 groups was improved compared with before treatment (P<0.05), and that in the observation group was better than the control group (P<0.05). The total effective rate of the observation group was 92.5% (37/40), which was higher than that of the control group (80.0%, 32/40, P<0.05).@*CONCLUSION@#Wheat grain moxibustion at Shixuan (EX-UE 11) combined with rehabilitation training can improve the hand motor function and daily living ability of patients with finger spasm after stroke, improve the degree of spasm and the function of wrist dorsiflexor muscle and flexor carpal metacarpal muscle, the clinical effect is better than simple rehabilitation training.

Mechanism of rhein inhibition of colorectal cancer through arginine metabolism based on protein chip / 药学学报

Rhein is an anthraquinone compound extracted from rhubarb, aloe vera, Polygonum multiflorum. In this study, we screened the potential targets of rhein through protein chip technology and investigated the underlying mechanism of its inhibition of colorectal cancer. Colony formation assay and scratch assay were used to examine the effect of rhein on the proliferation and migration abilities of HCT116 cell; KEGG and protein interaction analyses of rhein specific binding proteins by screening rhein binding proteins using protein chip; qRT-PCR and Western blot assays were used to determine the effect of rhein on the expression levels of BCL-2-associated X protein (BAX), B-cell lymphoma-2 (BCL-2) and argininosuccinate synthetase 1 (ASS1) in HCT116 cell. The antitumor effect of rhein was verified by azoxymethane combined with dextran sodium sulfate (AOM/DSS) induced colorectal cancer model. Experimental animal procedures were performed in accordance with animal welfare and the standards of the Laboratory Animal Ethics Committee of South China Agricultural University, with approval from the ethics committee. In vivo and in vitro results indicate that rhein specific binding proteins are mainly involved in amino acid anabolism, especially the arginine anabolic signaling pathway. Rhein inhibited the proliferation and migration of HCT116 cell in a concentration-dependent manner. Treated with rhein for 24 h significantly enhanced the expression of BAX and ASS1 in HCT116 cells, as well as the level of nitric oxide (NO) metabolism. In a mouse model of colorectal cancer, rhein significantly alleviated AOM/DSS induced weight loss and reduced fecal occult blood score. Meanwhile, rhein enhanced BAX and ASS1 expression in colon tumor tissue, as well as increased arginine and NO in serum. IHC and HE stain indicated that rhein alleviated Ki67 expression and macrophage infiltration in the colonic tissue of mice with AOM/DSS and delayed tumor formation. In conclusion, rhein can exert antitumor activity by regulating arginine and NO metabolism through ASS1.

The association of anxiety, depression, tinnitus and sleep quality in patients with occupational noise-induced deafness / 中国职业医学

OBJECTIVE: To investigate the status and association of anxiety, depression, tinnitus and sleep quality in patients with occupational noise-induced deafness(ONID). METHODS: A total of 302 ONID patients were selected as research subjects using judgment sampling method. Their status of anxiety, depression, tinnitus and sleep quality were investigated using questionnaires of Self-Rating Anxiety Scale, Self-Rating Depression Scale, Tinnitus Handicap Inventory and Pittsburgh Sleep Quality Index. RESULTS: Among the study subjects, there were 123 cases with no anxiety or depression, 46 cases with simple anxiety or depression, and 133 cases with combined anxiety and depression, accounting for 40.7%, 15.3% and 44.0%, respectively. The incidence of tinnitus and sleep disorder were 77.8%(235/302) and 48.0%(145/302), respectively. The total scores of tinnitus and sleep quality in simple anxiety or depression group were higher than those with no anxiety or depression(all P<0.01). The total scores of tinnitus and sleep quality in combined anxiety and depression group were higher than that with no anxiety and depression, and simple anxiety or depression group(all P<0.01). Among the research subjects, the incidence of tinnitus and sleep disorder from high to low were combined anxiety and depression group, simple anxiety or depression group, and no anxiety and depression group(tinnitus: 85.7% vs 76.1% vs 69.9%, sleep disturbance: 82.0% vs 37.0% vs 15.5%, all P<0.01). The standard scores of anxiety and depression in ONID patients were positively correlated with the total scores of tinnitus and sleep quality(correlation coefficients were 0.63, 0.72, 0.63, 0.69, all P<0.01). CONCLUSION: ONID patients can be accompanied by varying degrees of anxiety and depression. The existence of anxiety and depression may lead to increased tinnitus and decreased sleep quality in ONID patients.

Genetic study of cardiovascular disease subtypes defined by International Classification of Diseases / 北京大学学报(医学版)

OBJECTIVE@#To study the molecular connection among cardiovascular diseases (CVD) subtypes defined by the International Classification of Diseases (ICD) version 10 (ICD-10).@*METHODS@#Both phenotypic data and genotypic data used in this study were obtained from the UK Biobank. A total of 380 083 participants aged between 40 and 69 years were included. Those without any cardiovascular disease (either no ICD-10 code at all or no ICD-10 code containing letter I) were assigned to the control group. The five CVD subtypes were: ischaemic heart diseases (IHD), pulmonary heart disease and diseases of pulmonary circulation (PHD), cerebrovascular diseases (CRB), diseases of arteries, arterioles and capillaries (AAC), diseases of veins, lymphatic vessels and lymph nodes, and diseases not elsewhere classified (VLL). We first performed a genome-wide association study (GWAS) for each of the five subtypes. We summarized novel loci using genome-wide significance threshold P=5×10-8. Next, we used linkage disequilibrium score regression (LDSC) method to assess genetic correlation among the five subtypes. Lastly, we applied mendelian randomization (MR) approach to assess the causal relationship among the subtypes. The particular software that we used was generalised summary-data-based mendelian randomisation (GSMR).@*RESULTS@#Through GWAS, we identified hundreds of genome-wide significant SNPs: 672 for IHD, 241 for PHD, 31 for CRB, 48 for AAC, and 193 for VLL. By comparing with published literature, we found 28 novel loci, for PHD (n=14), CRB (n =7) and AAC (n =7). Eight of these 28 loci were rare, where the lead SNP had minor allele frequency (MAF) less than 1%. LDSC analyses indicated IHD had significant genetic correlation with VLL (P=2.52×10-7), PHD (P=3.77×10-3) and AAC (P=4.90×10-3), respectively. Bidrectional GSMR analyses showed that IHD had a positive causal relationship with VLL (P=7.40×10-5) and AAC (P=1.50×10-3), while reverse causality was not supported.@*CONCLUSION@#This study adopted an innovative approach to study the molecular connection among CVD subtypes that are defined by ICD. We identified potentially positive genetic correlation and causal effects among some of these subtypes. Research along this line will provide scientific insights and serve as a guidance for future ICD standards.

Mouse strain-specific responses of mitochondrial respiratory function and cardiac hypertrophy to isoproterenol treatment / 生理学报

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases and eventually develops into heart failure. This paper was aimed to study the different pathological characteristics exhibited by different mouse strains after hypertrophy stimulation. Two mouse strains, A/J and FVB/nJ, were treated with isoproterenol (ISO) by osmotic pump to induce cardiac hypertrophy. Echocardiography was performed to monitor heart morphology and function. Mitochondria were isolated from hearts in each group, and oxidative phosphorylation function was assayed in vitro. The results showed that both strains showed a compensatory enhancement of heart contractile function after 1-week ISO treatment. The A/J mice, but not the FVB/nJ mice, developed significant cardiac hypertrophy after 3-week ISO treatment as evidenced by increases in left ventricular posterior wall thickness, heart weight/body weight ratio, cross sectional area of cardiomyocytes and cardiac hypertrophic markers. Interestingly, the heart from A/J mice contained higher mitochondrial DNA copy number compared with that from FVB/nJ mice. Functionally, the mitochondria from A/J mice displayed faster O

Research progress of aristolochic acids and their biomarkers / 药学学报

Aristolochic acids (AAs) are widely distributed in Aristolochiaceae, and are important toxic components in medicinal plants of Aristolochiaceae. As one of the most powerful carcinogens in the Carcinogenic Potency Database (CPDB), AAs can induce hepatotoxicity, nephrotoxicity, carcinogenicity, mutagenicity, and other adverse reaction. AAs also can produce a series of metabolites such as AA-DNA adducts in the body, and their specific metabolites can be used as biomarkers for early diagnosis and treatment of related diseases. Thus, the current discovery for technical means that can quickly and accurately detect biomarkers possesses significant research value. AAs can be attenuated by processing, compatibility, molecular breeding, and other methods to improve the clinical safety of Chinese medicine containing AAs. In this review, we report the distribution of AAs, attenuation strategies and biomarker detection. We would like to provide a reference for the quality control of AAs-containing Chinese medicines, as well as for the prevention and control of diseases caused by AAs.

Qualitative and Quantitative Analysis of Aristolochic Acids in Aristolochia cinnabarina Dried Root Tubers by UPLC-QTOF-MS/MS / 中国实验方剂学杂志

Objective:To establish a qualitative and quantitative method for the determination of aristolochic acids in <italic>Aristolochia cinnabarina</italic> dried root tubers. Method:The dried root tubers of <italic>A. cinnabarina </italic>was qualitative and quantitative analysis by ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-QTOF-MS/MS）. The analysis was performed on Waters ACQUITY UPLC-BEH C₁₈ column （ 2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-1 min， 10%B； 1-9 min， 10%-30%B； 9-11 min， 30%-50%B； 11-15 min， 50%-90%B）. The flow rate was 0.45 mL·min^-1， column temperature was 35 ℃， and the detection wavelength was 250 nm. Mass spectral data was acquired in positive mode of electrospray ionization （ESI）. At the same time， the UPLC fingerprints of aristolochic acids in 21 batches of <italic>A. cinnabarina</italic> dried root tubers were established， and the contents of 5 aristolochic acids in <italic>A. cinnabarina</italic> dried root tubers from different producing areas and different harvesting periods were determined. Result:A total of 17 compounds， including 8 aristolochic acids， 7 aristololactams and 2 4，5-dioxoaporphine alkaloids， were identified from <italic>A. cinnabarina</italic> dried root tubers by mass spectrometry data and bibliographic information. Ten common peaks were identified in the UPLC fingerprint， and they were tuberosinone-<italic>N</italic>-<italic>β</italic>-<italic>D</italic>-glucoside， aristolactam Ⅰa-<italic>N</italic>-<italic>β</italic>-<italic>D</italic>-glucoside， aristolochic acid Ⅳa-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucoside， aristolactam Ⅲa-<italic>N</italic>-<italic>β</italic>-<italic>D</italic>-glucoside， aristolactam Ⅰ-<italic>N</italic>-<italic>β</italic>-<italic>D</italic>-glucoside， aristolochic acid Ⅲa， aristolochic acid Ⅳa， aristolochic acid Ⅱ， aristolactam Ⅰ and aristolochic acid Ⅰ. According to the quantitative analysis， the results exhibited that aristolochic acid Ⅲa， aristolochic acid Ⅳa， aristolochic acid Ⅱ， aristolactam Ⅰ and aristolochic acid Ⅰ had good linear relationships in the linear range. The relative standard deviations （RSDs） of precision， stability and reproducibility tests were all less than 3.0%， the recovery was 97.06%-101.84% （RSD<3.0%）. The contents of aristolochic acid Ⅰ， aristolochic acid Ⅱ， aristolochic acid Ⅲa， aristolochic acid Ⅳa， and aristolactam Ⅰ in 21 batches of <italic>A. cinnabarina</italic> dried root tubers were 0.938 6-3.567 5， 1.377 6-3.688 1， 0.056 3-0.527 7， 0.108 8-0.305 5， 0.021 0-0.081 7 mg·g^-1， respectively. Conclusion:The content of aristolochic acids in <italic>A. cinnabarina</italic> dried root tubers has a certain difference， the contents of aristolochic acid Ⅰ and Ⅱ are higher than other aristolochic acids. The established method is rapid， simple， accurate and reliable， which can provide reference for the quality control and evaluation of <italic>A. cinnabarina</italic> dried root tubers.

Effect of miR-373 on rats with diabetic retinopathy by targeting VEGFA / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the effect of microRNA-373(miR-373)by targeting vascular endothelial growth factor A(VEGFA)on diabetic retinopathy(DR)rats.<p>METHODS: Totally 40 rats were randomly divided into control group(<i>n</i>=10)and DR group(<i>n</i>=30). The rats after successful modeling in DR group were divided into model group(<i>n</i>=10), miR-373 agomir group(<i>n</i>=10), and agomir-NC group(<i>n</i>=10). The right eyes vitreous cavity separately were injected with 200μL normal saline, miR-373 agomir(200nmol)and agomir-NC(200nmol)were treated once a week for 12wk. The expression levels of miR-373 and VEGFA mRNA in each group were detected by RT-qPCR. Dual luciferase experiment was used to verify the targeting relationship between miR-373 and VEGFA. Western-blot was used to detect VEGFA, Bcl-2 related X protein(Bax), b-cell lymphoma-2(Bcl-2), phosphatidylinositol 3-kinase(PI3K)and phospho phosphatidylinositol 3-kinase(p-PI3K), serine threonine protein kinase(AKT), phospho serine protein kinase(p-AKT)protein expression levels.<p>RESULTS: Compared with the control group, the expression levels of miR-373 and Bcl-2 protein in the retina tissue of model group and agomir-NC group were significantly decreased, and the expression levels of VEGFA mRNA, Bax, p-PI3K and p-AKT protein were significantly increased. Compared with the agomir-NC group, the expression levels of miR-373 and Bcl-2 protein in the retina tissue of miR-373 agomir group were significantly increased(all <i>P</i><0.05), while the expression levels of VEGFA mRNA and protein, the Bax, p-PI3K, p-AKT protein in the retina tissue of miR-373 agomir group were significantly decreased(all <i>P</i><0.05). Dual luciferase assay confirmed that VEGFA is the target gene of miR-373.<p>CONCLUSION: miR-373 can inhibit diabetic retinopathy by targeting VEGFA, which may be related to the inhibition of PI3K/AKT signaling pathway by miR-373.

Molecular identification and alkaloids content of endangered Chinese medicinal plant Coptis chinensis var. brevisepala / 中国中药杂志

According to the records of Chinese materia medica,Coptis chinensis var. brevisepala is an authentic Chinese medicinal plant highly recommended by ancient physicians since its rhizome is like a string of beads and has a good medicinal value. However,its medicinal components and values remain to be studied as it is endangered because of overexploitation. Therefore,this study aims to quantitatively determine its effective components based on UPLC-QTOF-MS,and to compare the contents of isoquinoline alkaloids in C.chinensis var. brevisepala with those in other Coptis species. Meanwhile,molecular methods accurately identified 12 batches of C. chinensis var. brevisepala,9 batches of C. chinensis,4 batches of C. deltoidea,and 1 batch of C. teeta. Gradient elution was performed with Waters CORTECS C18 column( 4. 6 mm× 150 mm,2. 7 μm) and the mobile phase acetonitrile-water with 0. 4% formic acid. Mass spectrometry was conducted in ESI positive mode. The quantitative results showed that 8 main alkaloids had a good linear relationship within the concentration range( R~2>0. 996),with the recovery rate of 95. 18%-105. 0% and the RSD of 0. 28%-3. 7%. Compared with that of other Coptis species,the rhizome of C. chinensis var. brevisepala had the highest contents of berberine and columbamine. The total content of the 8 alkaloids in C. chinensis var. brevisepala was similar to that in C. chinensis but higher than that of the other two species. PCA was performed to compare the alkaloids among the 4 species. Besides,the 8 alkaloids were evaluated in different parts of C. chinensis var. brevisepala. The results indicate that this method is reliable and efficient and can provide a reference for the quality research.

Research progress on medicinal resources of Coptis and its isoquinoline alkaloids / 中国中药杂志

Coptidis Rhizoma is a common Chinese medicinal in clinical practice,with the effects of clearing heat,drying dampness,purging fire,and removing toxin. All the medicinal plants of Coptis can be used for clinical treatment,but some species are endangered due to resource destruction and difficulty in planting. The dominant medicinal components in Coptidis Rhizoma are isoquinoline alkaloids. There are various methods for the analysis and detection of alkaloids,such as LC-MS,HPLC,and TLC,among which LC-MS is the most widely applied. Different plants of Coptis vary in the kind and content of alkaloids. C. chinensis,C. deltoidea,C. teeta,C. chinensis var. brevisepala,C. omeiensis,C. quinquefolia,and C. quinquesecta mainly contain berberine,palmatine,coptisine,jatrorrhizine,and columbamine,five effective alkaloid components. Plant isoquinoline alkaloids( PIAs) have strong pharmacological activity but are difficult to prepare. The application of synthetic biology of PIAs will be helpful for the clinical application of PIAs. This paper reviews the research progress on biological resources of Coptis species and structures of alkaloids as well as analysis methods and synthetic biology for isoquinoline alkaloids in the medicinal plants of Coptis in recent years,which will facilitate the protection of Coptis medicinal resources and the application and development of alkaloids.

Design and Test of Automatic Dispensing and Injecting System for Positron Radiopharmaceuticals / 中国医学科学院学报

Objective To design a novel automatic dispensing and injecting system of positron radiopharmaceuticals,for precise dose dispensing,simplified operation,and reduction of occupational radiation exposure. Methods The automatic dispensing and injecting system was fabricated with tungsten alloy as the shielding material.The performance and radiation protection of the device were assessed. Results The total time of injection using the automatic dispensing and injecting system was about 60 s.The ratio of successful injection in stability test was 100%.The deviation of the dispensing dose with the system was ≤3%.With the tungsten alloy shield(40 mmPb of the cabinet,60 mmPb of the countertop,15 mmPb of the protective shield,and 50 mmPb of the inbuilt jar for radiopharmaceuticals),the average dose rate at 30 cm from the device was 1.44 μSv/h,and the radiation dose at the operator's extremity was reduced by 99%. Conclusions This automatic dispensing and injecting system of positron radiopharmaceuticals is easy to operate with precise dispensing dose.It is safe and meets the requirements of radiation protection.

A case of 16p13.11 microdeletion syndrome with febrile convulsion as the main manifestation / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a girl with febrile convulsion as the main manifestation.@*METHODS@#The child was subjected to whole exome sequencing (WES) and copy number variation sequencing(CNV-seq). Fluorescence quantitative PCR was carried out to validate the microdeletion in her family.@*RESULTS@#The 7-year-old girl was diagnosed with febrile convulsion (complex type) for having fever for 3 days, mild cough and low thermal convulsion once. Her father, mother and aunt also had a history of febrile convulsion. A heterozygous deletion with a size of approximately 1.5 Mb was detected in the 16p13.11 region by WES and CNV-seq. The deletion has derived from her father and was confirmed by fluorescence quantitative PCR.@*CONCLUSION@#16p13.11 microdeletion syndrome has significant clinical heterogeneity. Different from those with epilepsy, mental retardation, autism, multiple malformations, carriers of 16p13.11 deletion may only manifest with febrile convulsion. Deletion of certain gene(s) from the region may be related to febrile convulsion and underlay the symptom of this child.

Regulatory Effect of Yangxue Jiedu Decoction on Tight Junction of Keratinocytes in Psoriasis / 中国实验方剂学杂志

Objective::To observe the expressions of tight junction proteins (claduin-1, claudin-7 occludin)of psoriasis-like lesions in mice, and clarify the effect of Yangxue Jiedu decoction on the epidermal barrier of psoriasis, so as to provide scientific basis for the treatment of psoriasis with Yangxue Jiedu decoction. Method::C57BL/6J mice were randomly divided into control group, model group, methotrexate group and Yangxue Jiedu decoction.Methotrexate solution and water decoction of Yangxue Jiedu decoction were prepared, and the mice were given imiquimot to induce psoriasis-skin lesions after the hair was shaved.Daily photos were taken to record the forms of skin lesions and psoriasis area and severity index(PASI) scores.Water and oil test pens were used to detect skin moisture content. The pathological changes were observed by htoxylin eosin (HE) staining, and the epidermal thickness was measured.Ki67 was detected by immunofluorescence. Immunohistochemistry was used to detect the expressions of loricrin, CD3+ T lymphocyte infiltration and claduin-1, claudin-7, occludin.In addition, the expressions of claudin-7 and occludin in skin lesions were detected by Western blot.Meanwhile, interleukin-17(IL-17) (1 mg·L-1) was used to simulate the microenvironment of psoriasis skin lesions, and the intervention was conducted by making Yangxue component, Jiedu component and Yangxue Jiedu dry powder.The toxicity of the drug on Hacat cells was detected by cell counting kit-8(CCK-8)method.The effect of the drugs on the expressions of claudin-1, claudin-7, occludin in Hacat was detected by immunofluorescence assay. Result::Yangxue Jiedu decoction could significantly reduce the psoriasis skin lesions in mice, and reduce the PASI score and skin thickness (P<0.01). Compared with the model group, the skin moisture content in the lesion was increased (P<0.01). Abnormal expressions of ki67 and loricrin in epidermis and infiltration of CD3+ T cells were reduced (P<0.01). In addition, the expressions of claudin-1, claudin-7, occludin proteins (P<0.05), and the integrity of the tight junction structure were increased.In vitro studies, compared with the model group, the expressions of claudin-1, claudin-7, and occludin in the Yangxue Jiedu group and Yangxue group were increased (P<0.05). Compared with the model group, there was no statistically significant difference in protein expression in the Jiedu group. Conclusion::By regulating the expressions of tight junction proteins between keratinocytes, Yangxue Jiedu decoction can inhibit the abnormal proliferation and differentiation, and further restore the broken epidermal barrier.Yangxue Jiedu decoction plays a role in regulating tight junction mainly through Yangxue component.

Expression of phospholipase A2 receptor antigen in idiopathic membranous nephropathy and its association with clinical features and prognosis / 中国医师杂志

Objective:To explore the relationship of phospholipase A2 receptor (PLA2R) antigen expression in renal tissue with clinical characteristics, prognosis of idiopathic membranous nephropathy (IMN) patients.Methods:292 patients with nephropathy diagnosed by renal biopsy from January 2008 to January 2018 were selected, including 156 cases of IMN, 45 cases of secondary membranous nephropathy, and 91 cases of non membranous nephropathy. The PLA2R antigen in renal tissues of each patient was detected by immunofluorescence. Patients with IMN were further divided into PLA2R antigen positive group (116 cases) and PLA2R antigen negative group (negative group, 40 cases), and the clinical characteristics and prognostic indicators of the two groups were compared and analyzed.Results:The positive rates of PLA2R antigen in IMN, secondary membranous nephropathy and non membranous nephropathy were 74.4%(116/156), 11.1%(5/45) and 0, respectively. The positive rate of PLA2R antigen in IMN was the highest (χ 2=16.338, P=0.006). In IMN patients, the majority of IMN patients were stage I membranous nephropathy (90%, 36/40) and stage II membranous nephropathy (62.9%, 73/116) in the positive group (χ 2=8.230, P=0.029). The complete remission rate of the negative group (79.4%, 27/34) was significantly higher than that of the positive group (43.6%, 44/101), and the difference was statistically significant (χ 2=10.656, P=0.021). Conclusions:The expression of PLA2R antigen in renal tissue plays an important role in the diagnosis of IMN, and it′s correlated with the pathological stage of IMN. The negative PLA2R in kidney tissue of IMN may indicate a good clinical prognosis.

Association of single nucleotide polymorphism at the estrogen receptor 1 gene rs1801132 with the risk of brick-tea type skeletal fluorosis / 中华地方病学杂志

Objective:To investigate the association of single nucleotide polymorphism at the estrogen receptor 1(ESR1) gene rs1801132 with the risk of brick-tea type skeletal fluorosis.Methods:The typical brick-tea type fluorosis areas in Qinghai, Xinjiang, and Inner Mongolia were selected as the survey sites for a cross-sectional study. An epidemiological questionnaire was conducted by the staffs on the sites for participants older than 16 years, and physical examination and X-ray diagnosis were performed. Brick tea, blood, and urine samples were collected at the same time. The diagnosis of skeletal fluorosis through X-ray was based on the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS/T 192-2008); The determination of tea's fluoride and urinary fluoride was performed by fluoride ion-selective electrode method; gene sequencing analysis of rs1801132 locus of ESR1 gene was done by Sequenom MassARRAY flight mass spectrometry system.Results:A total of 994 patients were included in this study. The total prevalence of skeletal fluorosis was 23.9% (238/994). The prevalence of skeletal fluorosis in Tibetans(39.9%, 123/308) was higher than those of Mongolian and Han nationality [22.2% (58/261), 13.4% (57/425), χ 2=20.435, 67.811, P < 0.05]. Based on binary logistic analysis, the daily tea fluoride intake ≤ 3.5 mg, urinary fluoride content ≤1.6 mg/L, and age ≤45 years were used as the reference groups, and then, when the daily tea fluoride intake > 7.0 mg ( OR=2.865, 95% CI: 1.923-4.268), urinary fluoride content > 1.6-3.2 mg/L ( OR=2.368, 95% CI: 1.686-3.326) and > 3.2 mg/L ( OR=3.559, 95% CI: 2.401-5.276), the age > 45-65 years old ( OR=2.361, 95% CI: 1.603-3.477) and > 65 years old ( OR=4.556, 95% CI: 2.845-7.296), the risk of fluorosis was higher than that of the reference group, respectively. When the daily tea fluoride intake was > 3.5-7.0 mg and the level of urinary fluoride was > 1.6-3.2 mg/L, G allele had a protective effect on skeletal fluorosis in Mongolian population (adjusted OR=0.207, 95% CI: 0.044-0.974); when the daily tea fluoride intake was > 3.5-7.0 mg, gender was male group, G allele had a protective effect on skeletal fluorosis in Han population (adjusted OR=0.315, 95% CI: 0.112-0.887). Conclusion:The single nucleotide polymorphism of the rs1801132 locus at the ESR1 gene may be associated with the risk of susceptibility to brick-tea type skeletal fluorosis in Mongolian and Han nationality.

Research progress on the relationship between microRNA and imbalance of bone turnover in skeletal fluorosis / 中华地方病学杂志

Skeletal fluorosis is an endemic disease prevalent in many countries in the world. China is one of the countries most affected by endemic fluorosis. The typical pathological change of skeletal fluorosis is accelerated bone turnover in bone tissue, during which a large number of transcription factors, signaling proteins and signaling pathways are expressed abnormally. However, the specific mechanism is not completely clear. MicroRNAs (miRNAs) are single-stranded non-coding RNA molecules involved in post-transcriptional regulation of genes. Studies have shown that miRNA can regulate the proliferation and differentiation of osteoblasts and osteoclasts, and is an important regulator of biological organ development and bone metabolic diseases. In this paper, the possible role of miRNA in the occurrence and development of skeletal fluorosis was discussed to provide ideas and directions for further study on the pathogenesis of skeletal fluorosis.

Determination of Total Polysaccharides in Decoction Pieces of Polyporus with Different Sources and Different Grades / 中国实验方剂学杂志

Objective: To establish a method for determining the content of total polysaccharides in decoction pieces of Polyporus,analyze the content of total polysaccharides in samples with different sources and grades. Method: The relative molecular weight and the polydispersity index of polysaccharides in decoction pieces of Polyporus were measured by a high performance gel chromatography coupled with a multi-angle laser light scattering and refractive index system.Dextran with similar molecular weight as polysaccharides was selected as the reference substance.Orthogonal experiment and single factor tests were used to optimize the pretreatment conditions for the determination of total polysaccharides in Polyporus.Polysaccharides in Polyporus with different areas and grades were determined by anthrone-sulfuric acid colorimetric method at 630 nm. Result: The linearity,stability,precision,repeatability and recovery rate of the established method all reached the standards,respectively.The content of total polysaccharides in samples from different areas ranged from 0.87% to 1.39%.The content of total polysaccharides in samples with different grades was 1.40% for first-grade pieces,1.21% for second-grade pieces, and 1.03% for third-grade pieces. Conclusion: The established method is simple,accurate and reproducible,and it can be used for the determination of polysaccharides in decoction pieces of Polyporus.The content of polysaccharides in samples from different origins varies greatly.The content of polysaccharides in samples with different grades shows a certain regularity.The content of polysaccharides is the highest in the first-grade pieces,followed by the content in the second-grade,and the lowest in the third-grade.The results can provide a reference for formulating limits for the content of total polysaccharides and the grade standard of decoction pieces of Polyporus.