Experience of LIN Yi in Disease-Syndrome-Syptom Differentiation and Treatment of Breast Cancer in Consolidation Phase / 中医杂志

This article summarized the clinical experience of Professor LIN Yi in applying the idea of disease-syndrome-syptom combination to the differentiation and treatment of breast cancer in consolidation phase. It is believed that the fundamental pathogenesis of breast cancer in consolidation phase is deficiency of healthy qi， so the treatment should emphasize on reinforcing healthy qi as the main and eliminating pathogen as the supplement. Commonly， Sijunzi Decoction （四君子汤）， Shenling Baizhu Powder （参苓白术散）， and Liuwei Dihuang Decoction （六味地黄汤） are used as the basic formula to strengthen the spleen and kidney to reinforce healthy qi， and Baihua Sheshe Cao （Scleromitrion diffusum ［Willd.］ R.J.Wang）， Yiyiren （Coix lacryma-jobi L.）， and ezhu （Curcuma aromatica Salisb.） are used to eliminate cancer toxin. It is also believed that the biological characteristics of different molecular subtypes of breast cancer are of great significance to the syndrome differentiation and treatment in traditional Chinese medicine， therefore， the formulas used in clinical practice are often selected taking into considerations of molecular subtypes of breast cancer. For those with positive sex hormone receptor， the most important thing is to replenish the congenital and benefit kidney essence， with modified Baihua Qiqi Decoction （白花芪杞汤）； for those with negative sex hormone receptor， the first step is to strengthen spleen and replenish kidneys， and it is especially important to strengthen the spleen with Baihua Qiling Decoction （白花芪苓汤）. At the same time， it is suggested that the primary and the secondary symptoms of patients should be differentiated， and the diseases and symptoms， as well as the modern medical laboratory indicators should be combined to give suitable medication.

Fournier gangrene with concurrent multifocal necrotizing fasciitis: a systematic review and case report

Purpose@#A patient presented to a regional surgical center with Fournier gangrene (FG) and concurrent multifocal necrotizing fasciitis (NF). Given the rarity, it was decided to undertake a systematic review to investigate the incidence and prevalence of FG with multifocal NF and consequently determine the treatment and approach to management of such presentation. @*Methods@#Firstly, the report of the 56-year-old male patient is discussed regarding his surgical management. Secondly, a systematic review was undertaken according to PRISMA guidelines using MEDLINE, Scopus, and Embase databases. Searches used the following MeSH terms: (“fournier’s gangrene”) AND ((necrotising fasciitis) OR (necrotising soft tissue infection)). Once the search results were obtained, duplicate articles were removed. Titles, abstracts, and articles were reviewed by 2 authors. @*Results@#The search strategy using the 3 databases revealed a total of 402 studies. Fifty-seven studies were removed due to duplication. A total of 345 records were screened via title and abstract, of which 115 were excluded. Two hundred and thirty studies were reviewed for eligibility. A total of all 230 studies were excluded; 169 were excluded as they included the incorrect patient population (patients suffered from FG or NF, but not both collectively), 60 studies were excluded due to incorrect study designs, and 1 report occurred in the wrong setting. @*Conclusion@#This highlights that while being a relatively known, uncommon infection both FG and NF are well documented separately within the literature. However, FG with concurrent multifocal NF has not been documented within the literature.

Clinical characteristics of children with autism spectrum disorders: a cross-sectional study of cases attended at three centers specializing in neurodevelopmental disorders in Kinshasa, Democratic Republic of Congo (DRC)

Context and objective. Autism spectrum disorders (ASD) in sub-Saharan African (SSA) countries are poorly studied. The aim of the present study was to describe the socio demographic and clinical characteristics of children with autism and to identify associated factors. Methods. This was a cross-sectional study of children with ASD attended at three specialized centers in Kinshasa. We confirmed a ASD diagnosis through clinical observation using Diagnostic and Statistical Manuel of Mental Disorders four Text Revision (DSM-VI-TR) criteria and standardized autism diagnostic tools. We analyzed socio-demographic and clinical characteristics and main comorbidities of ASD. The comparison of proportions was done using Pearson's chi-square test. One-way ANOVAs were calculated to test differences in averages. Results. A total of 120 children (72.5 % male) were examined. Their mean age at diagnosis was 7.83 ± 3.4 years, while parents were alerted at 1.8 ±0.78 years. Language delays were the main alert sign (54%) and the main symptom (62%). Social interaction disorders (11.7 %) were underreported by parents. The core signs of ASD were disorders of social interaction (90.5%), behavior (80%) and language (62.5%). The main ASD symptoms were associated with epilepsy(p=0.027), cerebral palsy (p=0.026) and hearing impairment (p=0.045). Conclusion. The diagnostic and language delay co-occurring with epilepsy and hearing impairment are the main clinical features of autism in the DRC. This study suggests that screening children for autism and its main comorbidities using a multidisciplinary approach should be a priority in Kinshasa.

Analysis of robot-assisted laparoscopic versus laparoscopic partial nephrectomy for the treatment of completely endophytic renal tumors / 中华泌尿外科杂志

Objective:To compare the efficacy and safety of robot-assisted laparoscopic and laparoscopic partial nephrectomy (RAPN and LPN) for patients with completely endophytic renal tumor.Methods:A total of 73 patients with completely endophytic renal tumor receiving RAPN (n=29) or LPN (n=44) in our center between January 2015 and June 2021 were retrospectively collected. There were 21 males and 8 females in RAPN group. The average age was 48.6±13.7 years old, average tumor size was 2.9±0.9 cm with 13 left tumors and 16 right tumors, average R. E.N.A.L. score was 9.2±1.0, and average preoperative eGFR was 82.6±10.7 ml/(min·1.73 m 2). There were 27 males and 17 females in LPN group. The average age was 50.1±12.3 years old, average tumor size was 2.9±0.9 cm with 24 left tumors and 20 right tumors, average R. E.N.A.L. score was 9.1±1.3, and average preoperative eGFR was 81.7±9.6 ml/(min·1.73 m 2). There was no significant difference in above variables between two groups. The operative time, warm ischemia time, blood loss, postoperative complication, postoperative hospital stay and postoperative 3 months renal function of two groups were compared. Results:All 73 patients successfully underwent RAPN or LPN and no patient converted to radical nephrectomy or open surgery. There was no significant difference in operation time [140(80, 160) min vs. 150 (90, 180) min, P=0.264], intraoperative estimated blood loss[150 (100, 200)vs. 180 (120, 200) ml, P=0.576]and postoperative hospital stay (7.0±2.7 vs. 7.4±2.1 days, P=0.480) between two groups. Compared with LPN group, RAPN group had obvious less warm ischemia time (23.1±3.3 vs. 27.6±4.7 min, P<0.001). No obvious complication occurred in RAPN group and one case with postoperative hemorrhage occurred in LPN group. No positive margin occurred in either group. There was no difference in renal function 3 months after operation between the two groups [73.2±6.3 vs.70.5±7.6ml/(min·1.73 m 2), P=0.117]. The median follow-up period was 22.6 months with no tumor recurrence or metastasis. Conclusions:For experienced surgeons, both RAPN and LPN are safe and feasible for patients with completely endophytic renal tumor. Compared with LPN, RAPN has advantages of perioperative curative effect, which could reduce the operating difficulty and shorten the warm ischemia time.

Whole exome sequencing analysis of a patient with 45,X/46,XY mosaicism and autism spectrum disorder / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing for a patient with 45,X/46,XY mosaicism and autism spectrum disorder (ASD).@*METHODS@#Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Trio-based whole exome sequencing and Sanger sequencing were carried out thereafter.@*RESULTS@#The proband and his father were found to harbor a heterozygous c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene. In addition, the proband was also found to harbor a de novo c.268C>T (p.Arg90Trp) missense variant of the MTRR gene. Based on guidelines of the American College of Medical Genetics and Genomics (ACMG), the c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene was predicted to be pathogenic (PVS1, PM1, PM2, PP3), while the c.268C>T (p.Arg90Trp) variant of the MTRR gene was predicted to be of uncertain significance.@*CONCLUSION@#Variants of the CACNA1I and MTRR genes, together with the chromosomal mosaicism, may have predisposed to the susceptibility to the ASD in this patient.

Study on the Toxicity Mechanism of Yunaconitine-induced Arrhythmia in Rats Based on Calcium Overload / 中国药房

OBJECTIVE：To study the toxicity mechanism of yunacotine-induced arrhythmia in rats. METHODS ：Totally 32 rats were randomly divided by random number table method into normal control group ，yunacotine low-dose and high-dose groups （0.09，0.14 mg/kg），aconitine group （positive control ，0.88 mg/kg），with 8 rats in each group. Administration groups were given the corresponding drugs once a day ，and normal control group was given the constant volume of normal saline ，for consecutive 7 d. After last intragastric administration ，the changes of electrocardiogram （ECG） were observed. The contents of adenosine triphosphate（ATP）in myocardial tissue and Ca 2+ in myocardial cells ，the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase as well as the protein expression of ranolidine receptor 2（RyR2）and Ca 2+-ATPase（SERCA2）in myocardial tissue were determined. RESULTS：Compared with normal control group ，time limit of QRS wave and QTc intervals of rats were prolonged significantly in yunaconitine low-dose group （P＜0.01）. The content of Ca 2 + in myocardial cells ， the ATP contents ， the activities of Ca2+-Mg2+-ATPase and Na +-K+-ATPase as well as the protein expression of SERCA 2 in myocardial tissue were reduced significantly （P＜0.05 or P＜0.01）. The heart rate of rats in yunaconitine high-dose group and aconitine group were increased significantly （P＜ 0.05 or P＜0.01），and time limit of QRS wave and QTc intervals were significantly prolonged （P＜0.01）；the content of Ca 2+ in myocardial cells was increased significantly （P＜0.01）；ATP content ，the activities of Ca 2+-Mg2+-ATPase and Na +-K+-ATPase，and protein expression of RyR 2 and SERCA 2 in myocardial tissue were decreased significantly （P＜0.01）. CONCLUSIONS ： Yunaconitine can induce arrhythmia in rats ，the mechanism of which may be associated with Ca 2+ overload that resulted from reducing the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase and down-regulating the expression of related calcium transporter RyR2 and SERCA 2.

Influence of comprehensive rehabilitation on postoperative functions in elderly patients with femoral intertrochanteric fracture / 中华创伤骨科杂志

Objective:To analyze the influence of comprehensive rehabilitation on postoperative functions in the elderly patients with femoral intertrochanteric fracture.Methods:From June 2015 to June 2019, 144 elderly patients were treated at Department of Orthopedics, China-Japan Friendship Hospital for femoral intertrochanteric fractures by internal fixation with proximal femoral nail anti-rotation (PFNA). Of them, 65 received comprehensive rehabilitation, including intervention measures for details, prevention and management of comorbidities and complications and active exercise of the injured limb, while 79 conventional rehabilitation. In the comprehensive rehabilitation group, there were 22 males and 43 females with an age of (76.6±6.7) years, and 18 cases of type 31-A1, 35 cases of type 31-A2 and 12 cases of type 31-A3 by the AO type. In the control group, there were 23 males and 56 females with an age of (75.2±7.0) years, and 25 cases of type 31-A1, 39 cases of type 31-A2 and 15 cases of type 31-A3 by the AO type. The 2 groups were compared in terms of visual analog scale (VAS), Harris hip score, Barthel index, postoperative ambulation time and complications at 6 months after operation.Results:The 2 groups were comparable because there was no significant difference between them in the preoperative or intraoperative general data ( P>0.05). The comprehensive rehabilitation group had a significantly lower VAS score (1.5±1.0), a significantly higher Harris hip score(83.9±5.4), a significantly higher Barthel index (81.6±5.4), significantly shorter postoperative ambulation time [(2.6±1.0) d], and a significantly lower incidence of complications [4.6% (3/65)] than the control group did [1.9±1.2, 80.2±7.9, 78.2±7.9, (3.2±1.4) d, 16.5%(13/79), respectively] (all P< 0.05). Conclusion:For elderly patients with femoral intertrochanteric fracture, comprehensive rehabilitation can significantly reduce complications, promote functional recovery of the hip, and speed up recovery of capabilities of daily living compared with conventional rehabilitation.

Structure modification and antimicrobial activity of novel cationic melittin analogues / 药学学报

Melittin exhibits high antibacterial potency against drug-resistant bacteria. However, the clinical utility of melittin is limited by its serious hemolytic activity. Thus, the need for developing novel melittin analogues with high antimicrobial activity and low hemolytic activity has grown. We designed, synthesized, and evaluated 20 novel melittin analogues with varying hydrophobic, polar or positively charged amino acids. The results showed that 8 compounds had antimicrobial activity (MIC: 1-4 μg·mL-1) against gram-positive pathogens equal to or better than that of melittin, and 16 compounds had low hemolytic activity (HC50 ≥ 11.9 μg·mL-1). Compounds 13 (MIC: 2-4 μg·mL-1) and 15 (MIC: 1-2 μg·mL-1) showed equal or better antimicrobial activity against both susceptible and resistant strains of Staphylococcus aureus and Enterococcus faecium compared to melittin (MIC: 4 μg·mL-1). Compound 13 (HC50: 24.0 ± 4.3 μg·mL-1) displayed noticeably decreased hemolytic activity compared to melittin (HC50: 5.3 ± 0.4 μg·mL-1). This work established a base for further study on the structure-activity relationships and structure-toxicity relationships of melittin.

Determination of brain death for a pediatric patient with pneumorrhagia on VA-ECMO: A case report / 中国小儿急救医学

Objective:In May 2019, the 2018 version of Criteria and practical guidance for determination of brain death in children in China was published, which was revised by Brain Injury Evaluation Quality Control Center of National Health Commission, making the determination of brain death for pediatric patients in China more standardized and orderly.However, there is currently lacking of direction for the implementation of the above criteria for determining brain death to patients supported on extracorporeal membrane oxygenation(ECMO) in China.We successfully completed the determination of brain death and the organ transplantation(as a donor)for a pediatric case with severe brain injury and pneumorrhagia supported by VA-ECMO in our PICU, which provided clinical references for the revision of the guidelines for determination of brain death for pediatric patients in China. Methods:By referring to the international guidelines of Determination of Brain Death/ Death by Neurologic Criteria: The World Brain Death Project published in JAMA in August 2020, we performed a determination of brain death for a case of pediatric patient with severe brain injury and pneumorrhagia supported by VA-ECMO(blood flow 720 to 750 ml/min, gas flow 600 mL/min, oxygen concentration 65% to 70%)in our PICU. Results:The results of the determination of brain death included: Glasgow coma scale was 2T, all brainstem reflexes disappeared, three confirmation tests(electroencephalography, transcranial Doppler, short latency somatosensory evoked potential)all met the criterias for determination of brain death, apnea test(AT)showed PaCO 2>60 mmHg and elevated >20 mmHg than that before AT.We performed twice determination of brain death, interval time was >12 h. Finally, we successfully completed the determination of brain death and the organ transplantation(as a donor)for the case. Conclusion:The successful experience in the determination of brain death in the pediatric patient with severe brain injury and pneumorrhagia supported by VA-ECMO will provide clinical references for the revision of the guidelines for determination of brain death for pediatric patients in China.

A study on KIF1A gene missense variant analysis and its protein expression and structure profiles of an autism spectrum disorder family trio / 中华医学遗传学杂志

OBJECTIVE@#To analyze the pathogenic variants of the KIF1A gene and its corresponding protein structure in an autism spectrum disorder (ASD) family trio carrying harmful missense variants in the KIF1A gene.@*METHODS@#The peripheral blood DNA of the patient and his parents was extracted and sequenced using whole exome sequencing (WES) technology and verified by Sanger sequencing. Bioinformatics software SIFT, PolyPhen-2, Mutation Taster, and CADD software were used to analyze the harmfulness and conservation of variants. The Human Brain Transcriptome (HBT) database was used to analyze the expression of the KIF1A gene in the brain. PredictProtein and SWISS-MODEL were further used to predict the secondary structure and tertiary structure of KIF1A wild-type protein and variant protein. PyMOL V2.4 was utilized to investigate the change of hydrogen bond connection after protein variant.@*RESULTS@#The WES sequencing revealed a missense variant c.664A>C (p.Asn222His) in the child's KIF1A gene, and this variant was a de novo variant. The harmfulness prediction results suggest that this variant is harmful. By analyzing expression level of KIF1A gene in the brain. It is found that KIF1A gene widely expressed in various brain regions during embryonic development. By analyzing the variant protein structure, the missense variant of KIF1A will cause many changes in the secondary structure of protein, such as alpha-helix, beta-strand, and protein binding domain. The connection of hydrogen bond and spatial structure will also change, thereby changing the original biological function.@*CONCLUSION@#The KIF1A gene may be a risk gene for ASD.

A rare acute presentation of intestinal malrotation in the elderly

Intestinal malrotation, a congenital anomaly of the midgut, typically presents in pediatrics age group with the most feared complication of midgut volvulus and its catastrophic sequelae. Midgut volvulus secondary to intestinal malrotation is a rare presentation in adults more so in the elderly. Its rarity portends a diagnostic dilemma for both the surgeon and radiologist. We report a 65-year-old man admitted following a referral with a 12-hour history of acute abdomen with an initial diagnosis of acute pancreatitis but later had laparotomy with intraoperative findings of a midgut volvulus and gangrenous ileal segment secondary to intestinal malrotation. This case emphasizes the importance of early diagnosis to prevent the disastrous complication of this disease. The rarity of this condition portends a formidable diagnostic challenge in adults hence the awareness of its possibility and a high index of suspicion is crucial in diagnosis.

Hepatitis E virus infection in buffaloes in South China / [Hepatite E infecção viral em búfalos no Sul da China]

Hepatitis E virus (HEV) infection is an important global public health issue. HEV infections are recognized as a zoonotic disease. Swine are believed to be the main reservoir of HEV. Recently, yaks, cows, and yellow cattle have been reported as new reservoirs of HEV. However, whether other species of cattle and buffaloes are sensitive to HEV infection is unknown. To investigate the prevalence of HEV infection in buffaloes, enzyme-linked immunosorbent assay (ELISA) and reverse transcription-nested polymerase chain reaction (RT-nPCR) were performed. Only one buffalo was positive to anti-HEV IgM antibody (1/106, 0.94%), and none were positive for anti-HEV IgG antibody. To our surprise, five serum (5/106, 4.72%) and three milk samples (3/40, 7.50%) from buffaloes were positive to HEV RNA. All strains of HEV isolated from buffaloes belong to genotype 4. Results indicate that buffaloes may be a new reservoir of HEV.(AU)

Infecção com o vírus Hepatite E (HEV) é uma importante questão de saúde pública global. Infecções HEV são reconhecidas como doença zoológica. Acredita-se que suínos são o principal reservatório de HEV. Recentemente iaques, vacas, e gado amarelo foram reportados como novos reservatórios do HEV. Porém, não se sabe se outras espécies de gado e búfalo são sensíveis a infecção HEV. Para investigar a prevalência de infecção HEV em búfalos, foram realizados prova de imunoabsorção enzimática e polimerização em cadeia inversa ancorada em transcrição. Apenas um búfalo foi positivo para o anticorpo anti-HEV IgM (1/106, 0,94%), e nenhum foi positivo para o anticorpo anti-HEV IgG. Para nossa surpresa cinco (5/106, 4,72%) e três amostras de leite (3/40, 7,50%) de búfalos foram positivos para HEV RNA. Todas as estirpes de HEV isoladas de búfalos pertencem ao genótipo 4. Resultados indicam que búfalos podem ser um reservatório de HEV.(AU)

Comparative Study of Fluoroscopy vs Ultrasound Guided Stellate Ganglion Block

Introduction: Stellate ganglion block (SGB) is used for thetreatment of many vascular disorders and sympatheticallymediated pain including pain of head, neck, cancer, phantom,postherpetic neuralgia, cardiac arrythmia, orofacial pain, andvascular headache. Various modalities to localize stellateganglion use of fluoroscopy, computerized tomography,magnetic resonance imaging, and radionucleotide tracers.Ultrasound imaging is a best tool for SGB due to its clarity,low cost, lack of radiation and portability. In this study weaimed to compare the efficacy of fluoroscopy vs ultrasoundguided stellate ganglion block in lowering the pain usingnumeric rating scale (NRS).Material and Methods: Study was perform in 40 patientssuffering from upper limb and head and neck, neuropathicpain. The first group (Group I) received stellate ganglion blockunder ultrasound guidance while the second group (Group II)received stellate ganglion block under fluoroscopy guidance.The t-test and Man Whitney test were perform to analyses thedata.Results: The requirement of different analgesia werecomparable in both group I and group II patients. Change inpain score was maximum at immediate post-block, 1 h postblock, 6 h post block (65.84% of baseline) while change wasminimum at 48 h post-block (48.45% of baseline). The painwas significantly lower in group I from baseline as comparedto group II at all periods. Range of Ease rating score were alsolower in group I. Block was statistically achieved earlier inGroup I (4.55±0.69 min) as compared to Group II (12.60±2.56min).Conclusion: USG and fluoroscopy are both good techniquesfor stellate ganglion block, but due to less complication, earlyblocking effect time, more precise placement of medicationultrasound guided block is preferred over fluoroscopy method.

Analysis of common genetic variants associated with neuro-synapse development among 60 family trios affected with sporadic autism spectrum disorders / 中华医学遗传学杂志

Objective@#To explore susceptibility genes for autism spectrum disorders (ASD).@*Methods@#Whole-exome sequencing was carried out for 60 family trios affected with sporadic ASD. Genetic variants discovered in over 10% of the patients were selected for genotype-phenotype correlation and pathway enrichment analysis using Phenolyzer software and metascape database. Combining gene-phenotypic scores, pathway-related genes associated with neural and neurite triggering were screened for the candidates.@*Results@#A total of 170 common variants were found to be associated with the ASD phenotype. Among these, there was only one high-confidence gene [SHANK2 (0.8146)] and four medium-confidence genes [ERBB2 (0.1322), LAMC3 (0.1117), PPFIA4 (0.1059), DISC1 (0.1002)]. Twenty-pathways and four biological processes were found to be statistically significant by pathway enrichment analysis, which included neuron projection morphogenesis (GO: 0048812), regulation of neuroblast proliferation (GO: 1902692), modulation of excitatory postsynaptic potential (GO: 0098815), and dendrite morphogenesis (GO: 0048813). Twenty-one genes were found to be closely associated with neurological and neurite triggering, among which only SHANK2, ERBB2, and DISC1 had above-medium confidence correlation scores with the ASD phenotypes.@*Conclusion@#Abnormal neuron projection morphogenesis (GO: 0048812) may be closely related to the occurrence of ASD. SHANK2, ERBB2, and DISC1 are susceptibility genes for ASD.

Analysis of common genetic variants associated with neuro-synapse development among 60 family trios affected with sporadic autism spectrum disorders / 中华医学遗传学杂志

OBJECTIVE@#To explore susceptibility genes for autism spectrum disorders (ASD).@*METHODS@#Whole-exome sequencing was carried out for 60 family trios affected with sporadic ASD. Genetic variants discovered in over 10% of the patients were selected for genotype-phenotype correlation and pathway enrichment analysis using Phenolyzer software and metascape database. Combining gene-phenotypic scores, pathway-related genes associated with neural and neurite triggering were screened for the candidates.@*RESULTS@#A total of 170 common variants were found to be associated with the ASD phenotype. Among these, there was only one high-confidence gene [SHANK2(0.8146)] and four medium-confidence genes [ERBB2(0.1322), LAMC3(0.1117), PPFIA4(0.1059), DISC1(0.1002)]. Twenty-pathways and four biological processes were found to be statistically significant by pathway enrichment analysis, which included neuron projection morphogenesis (GO: 0048812), regulation of neuroblast proliferation (GO: 1902692), modulation of excitatory postsynaptic potential (GO: 0098815), and dendrite morphogenesis (GO: 0048813). Twenty-one genes were found to be closely associated with neurological and neurite triggering, among which only SHANK2, ERBB2, and DISC1 had above-medium confidence correlation scores with the ASD phenotypes.@*CONCLUSION@#Abnormal neuron projection morphogenesis (GO: 0048812) may be closely related to the occurrence of ASD. SHANK2, ERBB2, and DISC1 are susceptibility genes for ASD.

Rapid detection of CYP2C9, CYP2C19,CYP4F2,VKORC1 and ABCB1 gene polymorphisms by liquid phase chip technology / 中华检验医学杂志

Objective@#To establish a method for simultaneous and rapid detecting of the polymorphisms in Cytochrome P450 2C9 (CYP2C9), CYP2C19, CYP4F2, Vitamin K epoxide reductase (VKORC1) and ATP-binding cassette subfamily B member1 (ABCB1) gene, which were associated with warfarin and clopidogrel, based on liquid phase chip technology.@*Methods@#Method establishment. The eight gene sequences near targeted sites related to warfarin and clopidogrel were found in Genbank, and the specific primers and probes were designed. Through multiple PCR amplification, followed by allele specific primer extension (ASPE), and MagPlex-Tag microspheres hybridization, the suspension array Luminex 200 system step-by-step, the genotypes were determined by fluorescence signal. The reaction system was optimized and its methodological evaluation was performed. 260 patients with antithrombotic therapy from Dongguan houjie hospital were recruited in this study form June 2017 to December 2018. The eight genotypes of the 260 patients were detected by the established method, and the results were compared with the sequencing results.@*Results@#The results of 260 samples showed that allelic median fluorescence intensity (MFI) ratios of homozygotes (mutant/wild-type) were all greater than 0.9 or less than 0.1, and all the allelic MFI ratios of heterozygotes were between 0.3 and 0.6. The within run and between run coefficients of variance for allelic MFI ratios were lower than 6.4% and 10.9%, respectively. The minimum DNA template requirements was 0.75ng. The genotypes of 260 patients determined by the established method were completely concordant with the sequencing results.@*Conclusion@#A method was established successfully for rapid detecting the genotypes which associated with warfarin and clopidogrel based on liquid phase chip technology.

Rapid detection of CYP2C9, CYP2C19, CYP4F2, VKORC1 and ABCB1 gene polymorphisms by liquid phase chip technology / 中华检验医学杂志

Objective To establish a method for simultaneous and rapid detecting of the polymorphisms in Cytochrome P4502C9 (CYP2C9), CYP2C19, CYP4F2, Vitamin K epoxide reductase (VKORC1) and ATP-binding cassette subfamily B member1 (ABCB1) gene, which were associated with warfarin and clopidogrel, based on liquid phase chip technology. Methods Method establishment. The eight gene sequences near targeted sites related to warfarin and clopidogrel were found in Genbank, and the specific primers and probes were designed. Through multiple PCR amplification, followed by allele specific primer extension (ASPE), and MagPlex-Tag microspheres hybridization, the suspension array Luminex 200 system step-by-step, the genotypes were determined by fluorescence signal. The reaction system was optimized and its methodological evaluation was performed. 260 patients with antithrombotic therapy from Dongguan houjie hospital were recruited in this study form June 2017 to December 2018. The eight genotypes of the 260 patients were detected by the established method, and the results were compared with the sequencing results. Results The results of 260 samples showed that allelic median fluorescence intensity (MFI) ratios of homozygotes (mutant/wild-type) were all greater than 0.9 or less than 0.1, and all the allelic MFI ratios of heterozygotes were between 0.3 and 0.6. The within run and between run coefficients of variance for allelic MFI ratios were lower than 6.4％and 10.9％, respectively. The minimum DNA template requirements was 0.75ng. The genotypes of 260 patients determined by the established method were completely concordant with the sequencing results. Conclusion A method was established successfully for rapid detecting the genotypes which associated with warfarin and clopidogrel based on liquid phase chip technology.

Extrahepatic damage characteristics and clinical manifestations of hepatitis E / 中华实验和临床病毒学杂志

Hepatitis E virus (HEV) is a pathogen of viral hepatitis that is considered to severely harm human health. HEV infection usually causes self-limited diseases. Chronic hepatitis E was reported in organ transplant recipients. HEV was considered as a hepatotropic virus, but multiple organs involvement causing various clinical symptoms was reported recently. The involved organs and the clinical manifestations of HEV infection are summarized in this review, which will benefit understanding the pathogenesis of HEV infection, and improving the clinical diagnosis.

Investigation and Analysis of Off-label Use of Estradiol Preparation in ART Patients of a Hospital / 中国药房

OBJECTIVE： To provide reference for rational use of estradiol （E2） preparation in clinic. METHODS： The medical records of outpatients receiving assisted reproductive technology （ART） and E2 preparation [Estradiol valerate tablets （EV）， Complex packing estradiol tablets/estradiol and dydrogesterone tablets （EP）， Estradiol gel （EG）] were collected from the reproductive medicine center of a hospital during Jan. 2016-Mar. 2017. Taking drug instruction as standard， the rationality of medical records was evaluated from aspects of indication， route of administration， contraindication， usage and dosage， treatment course， etc. At the same time， these patients were followed up by telephone or outpatient service， and their pregnancy outcomes and ADR were summarized. RESULTS： A total of 12 646 prescriptions were collected， and 7 222， 3 912， 181 and 1 331 prescriptions used EV， EP， EG and EV+EP， respectively. The types of off-label use included over-indication， over-route and over-contraindication， and the rates of off-label use rates were 100％， 11.73％ and 43.60％， respectively. A total of 5 868 ART patients were involved； 439 patients received fresh embryo transplantation， and 5 429 patients received frozen-thawed embryo transplantation， involving 720 and 11 926 prescriptions， respectively. The rates of off-label use of above E2 preparations were 100％ （except for fresh embryo transplantation patients using EG）. As of Feb. 2018， the infant-holding rates of ART patients using EV， EP， EG and EV+EP were 85.29％， 85.37％， 86.36％ and 85.45％， respectively. No relevant ADR and neonatal birth defect was found. CONCLUSIONS： The phenomenon of off-label use of E2 preparations is widespread in the reproductive medicine center of the hospital. Although there is no indication of related safety risks， evidence-based evaluation should be carried out by enlarging the sample size in clinical practice， and careful use.

Imaging changes in brain microstructural in long-term abstinent from methamphetamine-dependence / 中南大学学报(医学版)

To explore the mechanism for changes in brain microstructure in long-term abstinent from methamphetamine-dependence by using the diffusion tensor imaging (DTI).
 Methods: A total of 26 patients with long-term abstinent methamphetamine-dependence, whose abstinence time more than 14 months, and 26 normal controls all underwent cognitive executive function tests and DTI scans. We used voxel-based analysis to compare the fractional anisotropy (FA) and mean diffusivity (MD) to obtain the abnormal brain regions of DTI parameters between the two groups. Spearman correlation analysis was used to explore the correlation between FA, MD of the brain regions with abnormal parameters and cognitive executive function tests.
 Results: There were no statistical differences in the cognitive executive function tests between the two groups (P>0.05). Compared with the normal control group, the long-term abstinent from methamphetamine-dependence group showed the decreased FA in the right precuneus, right superior frontal gyrus, right calcarine, left inferior temporal gyrus and the increased MD in the right triangular part of inferior frontal gyrus, right precuneus, right posterior cingulate, right middle temporal gyrus, bilateral middle occipital gyrus, left superior parietal lobule, and lobule VIII of cerebellar hemisphere. The MD values of the right middle temporal gyrus in the long-term abstinent group were negatively correlated with the number of completions within 60 seconds (r=-0.504) and within 120 seconds (r=-0.464) .
 Conclusion: The DTI parameters in multiple brain regions from the methamphetamine-dependence patients are still abnormal after a long-term abstinence. DTI can provide imaging evidence for brain microstructural abnormalities in long-term abstinent from methamphetamine-dependence.