Herbal Textual Research on Alpiniae Officinarum Rhizoma in Famous Classical Formulas / 中国实验方剂学杂志

By reviewing ancient materia medica， medical books and modern literature， this paper conducted a systematic research on name， origin， scientific name evolution， producing area， quality， harvesting and processing methods of Alpiniae Officinarum Rhizoma. The results showed that Alpiniae Officinarum Rhizoma was first published in Mingyi Bielu， and its correct name was Gaoliangjiang. The mainstream origin of Alpiniae Officinarum Rhizoma used in the past dynasties is Alpinia officinarum， which is used to this day， while it used to be mixed with A. galanga because of the similar name and morphology. Alpiniae Officinarum Rhizoma produced in Danzhou and Leizhou was considered to be better in ancient times， and now it mainly produced in Guangdong， Guangxi and Hainan provinces. In addition， it has been concluded that Alpiniae Officinarum Rhizoma with reddish brown， sturdy and firm character， wrinkled skin， convex flesh， aromatic and spicy taste， and few branches is the best. In ancient times， Alpiniae Officinarum Rhizoma was commonly harvested in February and March， whereas it generally harvested in late summer or early autumn at present， and wild products are usually harvested before the rainy season in May. The main processing methods of Alpiniae Officinarum Rhizoma are cleansing and cutting， and some other methods are stir-frying or mixing with auxiliary materials. Based on the research results， it is suggested that the raw products of A. officinarum rhizomes or its processed products according to prescription requirements should be used in the development of famous classical formulas containing Alpiniae Officinarum Rhizoma.

Herbal Textual Research on Benzoinum in Famous Classical Formulas / 中国实验方剂学杂志

Benzoinum has a long history of medicinal use. In order to standardize its clinical use， the author made systematic textual research on the name， origin， evolution of scientific name， producing area， property， quality evaluation， harvesting and processing of Benzoinum by reviewing the ancient materia medica， medical books and modern literature. According to the research， the mainstream variety of Benzoinum recorded in ancient materia medica should be the dry resin of Styrax tonkinensis of Styracaceae. In addition to S. benzoin， which was also used in many applications. In modern times， S. benzoin was the mainstream， but in practice， it was mostly the resin of various plants of the genus Styrax， and then S. tonkinensis and S. benzoides were recorded as the main sources of Benzoinum. Nowadays， it mainly comes from S. tonkinensis. In ancient times， the producing areas of Benzoinum were Persia， Xirong， Annan and other places， whereas now are distributed in Indonesia， Sumatra， Thailand， Vietnam， and Fujian， Guizhou， Yunnan， Guangxi， Guangdong and other places in China， but most of the medicinal materials in China are imported. Traditionally， the medicinal materials of Benzoinum with properties of oily， waxy luster， brittle and fragile， strong aroma， sand feeling when chewing and no impurities are considered better. In antiquity， the harvesting time of Benzoinum was concentrated in July and August， while in modern times， it is harvested in summer and autumn， and collected in various ways， usually the trees are selected to be harvested if they are more than 10 years old， and the best quality being the first， milky resin collected when the time of cutting the trees is from April to June. In the past dynasties， the powdered resin was mainly ground and used in formulas， in addition， there were also records of wine steaming into paste and processing with honey， etc. The 1953 edition of Chinese Pharmacopoeia added records such as sevum benzoinatum and adeps benzoinatus， and now it is mostly used as powder into pills or powers， or used after processing with wine. Based on the results of textual research， it is suggested that although the dry resin of S. benzoin is not a medicinal variety of Benzoinum included in the 2020 edition of Chinese Pharmacopoeia， it has a long history of application and has some clinical value， so its medicinal feasibility can be explored in depth. In the development of famous classical formulas containing Benzoinum， the dry resin of S. tonkinensis or S. benzoin can be used， which should be used in medicine as powder after dried or processed according to the requirements of prescriptions.

Study on the influencing factors of hospitalization in a long-term follow-up cohort of 123 patients with Crohn′s disease / 中华消化杂志

Objective:To explore the influencing factors of hospitalization in patients with mild active Crohn′s disease or in clinical remission during long-term follow-up.Methods:This was a prospective cohort study. From August 5, 2013 to January 5, 2015, 123 patients with mild active Crohn′s disease or in clinical remission visited the Department of Gastroenterology, Peking Union Medical College Hospital were selected. The baseline information of all the patients were collected, including the general data such as age and gender, clinical data such as extra-intestinal manifestations, complications, efficacy of glucocorticoid usage, serum hypersensitive C-reactive protein (hsCRP), serum albumin, and the total score and the subscore in systemic symptoms of inflammatory bowel disease questionnaire (IBDQ). All the patients were followed up for a long time till May 31, 2022 or the date of hospitalization due to the disease. Receiver operating characteristic curve (ROC) was used to define the optimal cut-off values of hsCRP and serum albumin for hospitalization prediction. Multivariate Cox regression model was used to analyze the influencing factors of hospitalization.Results:The median age of 123 patients was 32.0 years old (25.0 years old, 49.0 years old), 32.5% (40/123) were female, and 71 cases (57.7%) were hospitalized because of disease, and the median follow-up time was 29.2 months (9.0 months, 57.9 months). ROC analysis showed that the optimal cut-off value of hsCRP and serum albumin in predicting hospitalization because of disease in patients with Crohn′s disease was 1.5 mg/L and 40 g/L (both P<0.001), respectively.Multivariate Cox regression model showed that the extra-intestinal manifestations ( HR=1.869, 95% confidence interval (95% CI) 1.014 to 3.443), complications ( HR=2.511, 95% CI 1.368 to 4.608), glucocorticoid dependence or refractory ( HR=1.958, 95% CI 1.128 to 3.396), serum hsCRP≥1.5 mg/L ( HR=2.116, 95% CI 1.111 to 4.029) and serum albumin≤40 g/L ( HR=3.040, 95% CI 1.716 to 5.386) were independent risk factors of hospitalization because of disease in patients with Crohn′s disease ( P=0.045, 0.003, 0.017, 0.023, and <0.001). However, IBDQ subscore in systemic symptoms ( HR=0.873, 95% CI 0.805 to 0.948) was an independent protective factor of hospitalization because of disease ( P=0.001). Conclusions:Patients with Crohn′s disease at remission stage or mild activity stage who have extra-intestinal manifestations, complications, glucocorticoid dependence or refractory, serum hsCRP≥1.5 mg/L or serum albumin≤40 g/L are at high risk of hospitalization because of disease, and should be given more active treatments and more frequent follow-up. Patients with higher IBDQ subscore in systemic symptoms are more likely to gain a long-term stable condition.

Vestibular dysfunction in Wernicke encephalopathy / 中华神经科杂志

Objective:To analyze the abnormal vestibular function of Wernicke encephalopathy (WE) and to explore its diagnostic value.Methods:WE patients who visited the Vertigo Center of the Second Affiliated Hospital of Zhengzhou University from January 2018 to January 2021 were retrospectively collected. All patients were evaluated by clinical neurology. Before treatment, all patients completed video head impulse test (vHIT) and video nystagmusgraphy (VNG) in addition to cranial magnetic resonance and serum thiamine level examination.Results:All 12 patients had a history of eating defects, including 8 cases of alcoholism. All 12 patients had walking instability, 7 cases had dizziness and 8 cases had oscillopsia. Six cases had ophthalmoplegia. All 12 cases showed positive gaze nystagmus. The pathological saccades of bilateral horizontal semicircular canals were found in 12 patients by vHIT before treatment, but there was only 1 patient showing abnormality in vertical semicircular canals, the difference being statistically significant ( P<0.05). All patients could detect bilateral, horizontal, gaze-evoked nystagmus, including 3 cases with vertical nystagmus, 1 case with abnormal saccade test, 3 cases with abnormal smooth tracking test and 1 case with abnormal optokinetic test. There were abnormalities in the caloric test, including 6 cases of bilateral dysfunction and 2 cases of unilateral dysfunction. Conclusions:WE patients may have abnormal vHIT and bilateral, horizontal, gaze-evoked nystagmus, which is similar to the special abnormal signs of simultaneous damage of both peripheral and central vestibular dysfunction.Vestibular function test is valuable for diagnosis of WE, and it is suitable for patients with a history of nutritional disorders who have dizziness or walking instability and suspected WE.

Literature analysis of the design and results of the First-In-Human clinical trials of drugs from 2009 to 2020 / 中国临床药理学与治疗学

AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials. METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.

Design and implementation of electronic identity application for gene-directed personalized medicine / 中国临床药理学与治疗学

AIM: In order to bridge the gap between pharmacogenomic research and its clinical application, we propose the concept of genetic electronic identity, named "GeneFace", and developed an electronic information system which integrated "drug-gene" interactions and recommendations for personalized medicine. METHODS: Based on the self-developed Precision Medicine knowledgebase, which concludes drug directions, guidelines or important literatures with high level of evidence, we developed GeneFace with Java-based open-resource application framework Spring Boot, further developed a mobile App with cross-platform framework Uni-APP. RESULTS: The App includes six modules: genetic testing appointment, genetic knowledge introduction, individualized medication advice, medication records, Geneface interpretation, and Precision Medicine knowledgebase. By detecting the genotype of more than 300 gene loci upon first use, users import the results to form a personal "drug-gene identity card". Then scan or enter the drug name in "GeneFace", the App would automatically give corresponding medication recommendations, including: risks for possible adverse drug reactions, risks for reducing the efficacy or even ineffectiveness, and possibility for dose adjustment, etc., which increase the safety of clinical drug use. People can obtain pharmacogenomics knowledge and basic drug information in the "GeneFace" app. CONCLUSION: Development as a digital therapeutic product, the expanded application of GeneFace can rapidly promote clinical applications of basic pharmacogenomics research and significantly improve drug use safety, which creating a new model for accelerating the clinical application of personalized medicine.

Genetic variant analysis of a neonate with Cornelia de Lange syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect pathogenic variant in a neonate suspected for Cornelia de Lange syndrome (CdLS).@*METHODS@#Potential mutations of CdLS-related genes (NIPBL, SMC1A, SMC3, RAD21 and HDAC8) were detected by high-throughput target region capture and next-generation sequencing. Suspected variants was verified by Sanger sequencing.@*RESULTS@#The child was found to harbor a heterozygous splice site variant, c.6109-1G>A, of the NIPBL gene. Sanger sequencing suggested that neither parent has carried the same variant, suggesting that it was de novo. The variant was unreported by HGMD and ExAC database, and was predicted to alter an acceptor splicing site. No pathogenic variants of SMC1A, SMC3, RAD21 and HDAC8 genes were detected.@*CONCLUSION@#The heterozygous c.6109-1G>A splicing variant of the NIPBL gene may underlie the disease in this child. Above finding has expanded the variant spectrum of the NIPBL gene.

Improvement effect of dapagliflozin on liver function in patients with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the effect of dapagliflozin on the liver function of the patients with type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD), and to analyze its improvement effect on liver injury of the T2DM patients. Methods: The clinical data of 68 T2DM patients complicated with NAFLDS who did not receive any treatment were retrospectively analyzed, including 30 patients in acarbose group and 38 patients in dapagliflozin group, and the patients in two groups received acarbose 150 mg · d-1 + metformin 2 000 mg · d-1 and dapagliflozin 10 mg · d-1 + metformin 2 000 mg · d-1 treatment for 24 weeks, respectively. The general data of the patients before and after treatment were collected. The fasting venous blood of the patients in two groups was collected and the serum biochemical indexes and liver function indexes were detected. The serum biochemical indexes included fasting blood glucose (FBG) and glycosylated hemoglobin (HbAlc), and the homeostasis model assessment 2-insulin resistance index (HMOA2-IR) was calculated. The liver function indexes included aspartic transaminase (AST), alanine aminotransferase (ALT), glutamyltranspeptidase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), and direct bilirubin (DBIL); the non-alcoholic fatty liver disease fibrosis score (NAFLDFS) was calculated. The each detection index of the patients in two groups was compared and analyzed. Results: Compared with before treatment, the levels of FBG, HbAlc, AST, GGT, and ALP and HOMA2-IR in acarbose group after treatment were significantly decreased (P<0.01) and the levels of TBIL was significantly increased (P<0.01). Compared with before treatment, the levels of FBG, HbAlc, AST, ALT, GGT, and ALP and HOMA2-IR, NAFLDFS in dapagliflozin group were significantly decreased after treatment (P<0.01) and the levels of TBIL and DBIL were significantly increased (P<0.01). The levels of FBG, AST, ALT, GGT, and ALP and NAFLDF in dapagliflozin group after treatment were significantly decreased compared with acarbose group (P<0.01). Conclusion: Dagliflozin can improve the liver function of the patients with T2DM complicated with NAFLD, and its mechanism may be related to the effect of dapagliflozin decreasing the blood glucose and body weight.

Assessment of essential public health services in China based on WHO′s comprehensive evaluation model / 中华医院管理杂志

Objective@#To understand the current equalization in essential public health services in China, and to provide recommendations for health resource allocation and public health policy making.@*Methods@#WHO′s comprehensive evaluation model, and the Rank Sum Ratio (RSR) method were used to analyze, rank and categorize essential public health services.@*Results@#Thirty-one provinces (cities, autonomous regions) in China were grouped into five categories, namely, relatively balanced area, low input area, resource shortage area, over utilization area and resource waste area.@*Conclusions@#The equalization of essential public health services in China is gradually being realized, but there are still setbacks such as mismatch between health needs and resource input, waste and over-utilization of resources. To correct these problems, relevant recommendations on health policy making for different areas were given.

miR-362-3p Expression in Laryngeal Cancer Tissues and Its Effect on Migration of Hep-2 Cells / 中国医科大学学报

Objective To explore miR-362-3 p expression in laryngeal cancer tissues and its effect on migration of Hep2 cells. Methods miR-362-3 p expression in 50 pairs of tumor and adjacent normal tissues was detected by real-time PCR after sample collection. The relationships between miR-362-3 p expression and clinical pathological characteristics in patients with laryngeal cancer were analyzed.mi R-362-3 p mimic, inhibitor, and control microRNA were transfected into Hep-2 cells. Transfection efficiency was determined by real-time PCR. Wound-healing and transwell assays were used to evaluate Hep-2 migration. Results miR-362-3 p expression was significantly higher in cancer tissues than in adjacent normal tissues (P ＜ 0.05). miR-362-3 p expression was statistically significantly related to node metastasis and clinical stage. Transfection with miR-362-3 p mimic and inhibitor significantly increased and decreased Hep-2 cell migration, respectively (both P ＜ 0.05). Conclusion miR-362-3 p is up-regulated in laryngeal cancer tissues and promotes laryngeal cancer cell migration, suggesting that it acts as a potential oncogene in laryngeal cancer.

Relationship between prognostic nutritional index and neutropenia after chemotherapy in patients with colorectal cancer / 肿瘤研究与临床

Objective To investigate the relationship between prognostic nutritional index (PNI) and neutropenia after adjuvant chemotherapy in patients with colorectal cancer. Methods The clinical data of 44 patients with colorectal cancer performed adjuvant chemotherapy in Shunyi District Hospital from December 2014 to January 2018 were retrospectively analyzed, and the patients were divided into group A (grade 0-2 neutropenia) and group B (grade3-4 neutropenia) according to the degree of neutropenia. The serum albumin, peripheral lymphocyte counts, and neutrophil counts within 1 week before chemotherapy were collected, and the PNI was calculated. The chi-square test and rank sum test were used to compare the clinical data, body mass index (BMI), baseline neutrophil count, and PNI between the two groups. Logistic regression analysis was used to analyze the risk factors for neutropenia after chemotherapy. Results The baseline median neutrophil counts and median PNI in group A were 3.17×109/L [(1.38-7.79)×109/L] and 50.40 (37.40-57.05), and in group B were 2.54 ×109/L [(1.22-3.87) ×109/L] and 45.50 (37.95-50.95). The baseline neutrophil counts and PNI in group A were significantly higher than those in group B, the differences between the two groups were statistically significant (Z= -2.085, P= 0.037; Z= -2.615, P= 0.009). Logistic regression analysis showed that PNI was an independent risk factor for neutropenia after chemotherapy (HR=0.803, 95％CI 0.646-0.998, P= 0.048). Conclusion PNI has a certain role in predicting neutropenia after adjuvant chemotherapy in patients with colorectal cancer.

A case-control study of the association between the polymorphisms of APOE and SLCO1B1 and the severity of coronary artery disease / 中华检验医学杂志

Objective The single nucleotide polymorphisms (SNPs) of APOE and SLCO1B1 were examined to explore their association with the risk and severity of coronary heart disease(CAD). Methods A total of 1267 cases of consecutive coronary heart disease (CAD)-suspected inpatients visiting department of Cardiology in Peking University Peoples' Hospital from March 2017 to november were recruited into this case-control study, and then 391 CAD cases and 223 non-CAD controls were enrolled for final analysis after screening by coronary angiography and exclusion criteria. The severity of the CAD cases were evaluated according to Gensini scores. The SNPs of APOE(388T>C, 526C>T) and SLCO1B1(388A>G, 521T>C) were detected using Real-time PCR and further verified using Sanger sequencing. Environmental risk factors were collected, and the correlations between SNPs of APOE and SLCO1B1 and the risk and severity of CAD were performed by SPSS version 16.0. Results The SNPs of all the subjects included in CAD group and non-CAD group were successfully detected, with an accordance of 100％ to Sanger sequencing. The distribution of APOE and SLCO1B1 gene were subjected to Hardy-Weinberg. The distributions of APOE gene ε3/ε3 genotypes and ε3 allele were most commonly found in both CAD group and non-CAD group (ε3/ε3: 70.8％,73.1％;ε3: 83.5％,85.2％;respectively). APOE genotypes and alleles were comparable between the CAD cases and non-CAD controls (P>0.05). The frequencies of APOE gene ε4+genotype were more likely to be found in the subgroup of CAD with Gensini score≥72 (P<0.05). The distributions of SLCO1B1 gene *1b/*1b genotypes and *1b allele were most commonly found in both CAD group and non-CAD group (*1b/*1b: 37.3％, 36.8％; *1b: 60.1％, 61.7％; respectively). There was no significant difference in genotype and allele frequencies of SLCO1B1 between the two groups and among subgroups with different severity of CAD (P>0.05). Conclusion This study observed no association between SNPs of APOE, SLCO1B1 and the risk of CAD in this population. However, APOE gene ε4 +genotype may increase the severity of CAD.

The prevalence of common genetic deafness related mutation detected by microarray and follow-up in pregnant women in Beijing / 中华检验医学杂志

Objective To determine the distribution of common deafness gene mutations by microarray-PCR in pregnant women of Beijing, then explore their prevalence and clinical significance. Methods Totally 1709 pregnant women were prospectively enrolled from the outpatients of Obstetrical Clinical from Peking University Peoples' Hospital in this study from June 2016 to April 2018. Peripheral blood samples were obtained and DNA templates were extracted from all subjects. The coding region of the GJB2 gene(35del G, 235delC, 176-191del16, 299-300delAT), SLC26A4 gene(IVS7-2 A>G, 2168A>G), 12sRNA gene(1494C>T,1555A>G) and GJB3 gene(538 C>T)were detected by microarray-PCR. Meanwhile,256 cases firstly recruited in this study were confirmed by Sanger sequencing. The analysis was performed to explore the distribution of deafness gene mutations and the subjects detected to be positive were further followed up until they had given birth to their babies.Results Among 1709 pregnant women, 89 cases were found to be carrying at least one mutation sites(5.21％).Among them,83 cases were heterozygous mutation(35 cases of GJB2235delC, 12 cases of GJB2299-300delAT mutation, one case of GJB2176-191del 16, 30 cases of SLC26A4 IVS 7-2 A>G, 3 cases of SLC26A42168 A>G and two cases of GJB3538 C>T). There were one case of 235delC homozygous mutation and 2 cases of double mutations(IVS7-2 A>G /GJB2299-300delAT, IVS7-2 A>G/GJB2235delC). The positive rate of 235delC, 299-300delAT and 176-191del16 was 2.17％, 0.76％and 0.06％, respectively. As to SLC26A4, 1.87％of the pregnant women were carrying IVS 7-2 A>G and 0.18％for 2168 A>G. Two cases were detected carrying GJB3 C>T mutation and three for 12s RNA1555 A>G mutation, respectively. The results of microarray-PCR were identical to those of Sanger sequencing, with the coincidence of 100％.26 spouses of the 56 cases were followed up. Two proved to be carrier of the same gene mutation. One of their babies was born with normal hearing until the end of this research, while another baby was born deafness and implant cochlear when three month old. Conclusions GJB2235delC and SLC26A4 IVS 7-2 A>G were the most prevalent mutations in pregnant women of Beijing, and it may provide guidance to eugenics and early clinical intervention.

Study on Correlation of 5-hydroxytryptamine 2A Receptor Gene Polymorphism with Pain Occurrence and Opioid Require- ments in Patients with Lung Cancer / 中国药房

OBJECTIVE： To investigate the correlation of 5-hydroxytryptamine 2A receptor （5-HT2AR） rs6313 gene polymorphism with pain occurrence and opioid requirements in patients with lung cancer. METHODS： Totally 332 patients with lung cancer were selected from the Affiliated Hospital of Xuzhou Medical University during Dec. 2017-Jun. 2018 as lung cancer group. They were divided into pain group （177 cases） and painless group （155 cases） according to whether pain occurred. Totally 116 healthy persons who underwent physical examination in same period were selected as control group. The genotype of rs6313 locus of 5-HT2AR gene was detected by PCR-RFLP. The distribution of genotype was compared by χ2-test. The correlation of genotype with pain occurrence and degree， opioids requirements were investigated by Binary Logistic regression analysis， χ2-test and Kruskal-Wallis test. RESULTS： CC， CT， TT genotypes were detected in rs6313 locus of 5-HT2AR gene. The frequency of above genotypes were 20.7％， 47.4％， 31.9％， 20.6％， 50.3％， 29.0％ as well as 16.4％， 50.8％， 32.8％， respectively in control group， painless group and pain group. Their frequencies and allele frequencies were in line with Hardy-Weinberg balance （P＞0.05）. There was no statistical significance in genotype and allele frequencies between lung cancer group and control group （P＞0.05）. TNM staging （Ⅲ-Ⅳ stage） was associated with pain in lung cancer patients [OR＝3.661， 95％CI （1.972，6.797）， P＜0.001]. Gender， age， height， body weight， pathological typing and rs6313 locus genotype had no correlation with pain （P＞0.05）. The genotype of this locus was not related to the degree of pain and the requirements for opioids in patients with lung cancer （P＞0.05）. CONCLUSIONS： The polymorphism of 5-HT2AR gene rs6313 locus is no related to pain occurrence and opioid requirements in patients with lung cancer. Its polymorphism may not be the main cause of individual pain differences in lung cancer patients.

Application of next-generation sequencing in detection of breast cancer susceptibility genes BRCA1/2,TP53 and PTEN germline mutation / 中华检验医学杂志

Objective To investigate germline mutation of breast cancer susceptibility genes BRCA1/2,TP53 and PTEN in Chinese breast cancer patients. Methods All of128 female breast cancer patients in Peking University People′s Hospital from January 2016 to August 2018 were selected as objects. Among them,44 cases were sporadic breast cancer and 84 werebreast cancer patients with genetic high risks. Germline mutations of BRCA1,BRCA2,TP53 and PTENwere detected by NGS.χ2 test was used to analyze the difference of pathogenic mutation rates between sporadic breast cancer group and breast cancer with high genetic risks.Groups were divided according to the clinical features of the patients(family history, triple-negative breast cancer,age and bilateral breast cancer).Among them,there were 42 cases with family history of breast cancer,34 cases of triple-negative breast cancer,33 cases of early-onset breast cancer and 7 cases of bilateral breast cancer. Fisher′s exact probability test compared the relationship between pathogenic mutations of BRCA1/2 gene and clinical characteristics of breast cancer patients with hereditary risk factors. Results In 128 cases of breast cancer,30 germline mutations of BRCA1/2 were detected, including 13 pathogenic mutations and 3 newly discovered mutations(BRCA1:c. 4760C>G,BRCA2:c. 44134414del and BRCA2:c. 64826485del). The new mutations may be unique mutations of Chinese population. There were 3 cases of TP53 mutations,including 1 pathogenic mutation. All of the 3 mutations were found in early-onset breast cancer. Germline mutation of T53 has important detection significance for early-onset hereditary breast cancer. There were 5 cases of PTEN mutations,including 3 pathogenic mutations. Among 84 breast cancer patients with genetic high risks,the carry mutation rate was 40.5％(34/84)and the pathogenic mutation rate was 15.4(13/84). Among 44 sporadic cases,the carry mutation rate was 9％(4/44). The pathogenic mutation rate was 6.8％(3/44). Breast cancer susceptibility genes were carried at a higher rate in breast cancer patients with genetic high risks(P<0.001). BRCA1/2 mutations did not show statistical differences among groups of breast cancer patients with hereditary high risk factors . Conclusion Germline mutation detection of breast cancer susceptibility genes by next-generation sequencing is of great significance in breast cancer risk prediction and prognosis evaluation.

Research on differentiated marketing strategy of ASEAN market for development of Chinese patent medicine based on principal component analysis and hierarchical clustering method / 中草药

With high-tech, high added-value, and independent intellectual property rights, Chinese patent medicine (CPM) is one of the most important exporting categories in Chinese materia medica (CMM), and its overseas development has become an important symbol of international recognition for CMM. With the implementation of the Belt and Road Initiative and the acceleration of bilateral economic integration, CMM trade between China and Association of Southeast Asian Nations (ASEAN) is facing with great potential and opportunities. ASEAN market is bound to be a vital breakthrough in the globalization of CPM and has strategic significance for its transnational operation. Since ten member countries of ASEAN have obvious differences in their economic development, market size, and medical and health levels, this paper aims to establish evaluation index system, further subdivide the ASEAN market by means of principal component analysis and hierarchical clustering method, and put forward different marketing strategies for each segmented markets including developed market, emerging market, potential market, and secondary market, hoping to provide useful advice and reference for the globalization of CPM in ASEAN or even in European and American main market.

Immunomodulatory effects of Longdan Xiegan Tang on related inflammatory cytokines in rats with experimental autoimmune uveitis / 眼科新进展

Objective To study the immunomodulatory effects of Longdan Xiegan Tang on related inflammatory cytokines in rots with experimental autoimmune uveitis (EAU).Methods Lewis rats were randomly divided into control group (6 rats),EAU group (18 rats) and LXT group (18 rats).Rats in EAU and LXT groups were immunized with interphotoreceptor retinoid-binding protein (IRBP) emulsion.The expressions of IFN-γ,IL-17,IL-10 and TNF-α were investigated by quantitative real-time PCR and ELISA,respectively.Results In blood of LXT group,the mRNA level of IFN-γ on day 8 was higher than that in control group (P =0.000),but obviously lower than that in EAU group (P =0.000);The mRNA level of IL-17 was peaked on day 12,but was lower than EAU group (P=0.000);The mRNA level of TNF-α on day 12 was higher than that in control group (P =0.000),but obviously lower than that in EAU group (P =0.000);The mRNA level of IL-10 on day 16 was higher than that in EAU group (P =0.042).In lymph node and spleen of LXT group,the mRNA levels of IFN-γ,IL-17 and TNF-α on day 12 were lower than those in EAU group (all P=0.000);The mRNA level of IL-10 was peaked on day 12,but was lower than EAU group (P =0.000).In serum of LXT group,the mRNA levels of IFN--γ,IL-17 and TNF-α on day 12 and day 16 were lower than those in EAU group;The level of IL-10 in EAU and LXT group on day 12 were higher than that in control group,peaked on day 16,but the LXT group was the highest.Conclusion Longdan Xiegan Tang can reduce the expressions of proinflammatory cytokines including IFN-γ,IL-17 and TNF-α.Meanwhile,it can also promote the production of IL-10 and further accelerate the recovery of EAU,indicating that Longdan Xiegan Tang can play a significant role in treating uveitis.

Research progress on the relationship between sudden sensorineural hearing loss and serum lipids / 上海交通大学学报（医学版）

Sudden sensorineural hearing loss (SSHL),which is a common and frequently encountered disease,is considered to be a medical emergency in otolaryngology.The prevalence of SSHL is increasing in China.The pathogenesis of SSHL is not clear yet.Microcirculatory disorder of inner ear is considered as one of the most important causes of SSHL.In recent years,several reports have found the levels of serum lipids were changed in patients affected by SSHL.The relationship between SSHL and serum lipids was reviewed to provide new ideas for the diagnosis and treatment of SSHL.

Correlations between work engagement and transformational leadership among PICC specialized nurses / 现代临床护理

Objective To explore the correlations between work engagement and transformational leadership among PICC specialized nurses.Method A total of 176 PICC specialized nurses recruited from Shandong Province by convenience sampling method were involved in the study by the Utrecht work engagement scale (UWES-9) and transformational leadership scale.Results The average scores of work engagement and transformational leadership were (39.21±11.56) and (89.68±23.52).Work engagement dedication and absorption were positively correlated to transformational lendership (P＜0.05).Conclusion Hospital administrators should plan a clear direction for the development of the PICC specialized nurses to enhance their work engagement.

Tuberous sclerosis complex secondary to fetal heart occupying lesions: a case report and literature review / 临床儿科杂志

Objective To explore the clinical characteristics of tuberous sclerosis complex (TSC). Methods The clinical data of one child with TSC were collected. The clinical features and gene mutation were analyzed. Results A 36-day-old girl had abnormal nodules found by echocardiography, which was considered multiple cardiac rhabdomyomas. There were multiple hypomelanotic macules distributed over the skin surface of the trunk and legs. Cranial MRI showed cortical nodules, subependymal nodules and cerebral white matter radial migration line. A mutation in the TSC2 gene (c.4541-4544delCAAA) was found by second generation high-throughput sequencing technology and tuberous sclerosis complex was confirmed. Conclusion Gene detection is helpful in the early diagnosis of tuberous sclerosis complex.