Data mining of severe cutaneous adverse reactions related to immune checkpoint inhibitors in the FAERS / 中国药房

OBJECTIVE To mine and analyze severe cutaneous adverse reaction signals of 5 commonly used immune checkpoint inhibitors （ICIs）， and to provide reference for clinically safe use of drugs. METHODS Based on the FDA adverse events reporting system （FAERS） database，adverse drug events （ADEs） reports about severe cutaneous adverse reactions related to ipilimumab， nivolumab， pembrolizumab， atezolizumab and durvalumab were collected from listing in the United States to the fourth quarter of 2022. The ADE signals were mined and analyzed with reporting odds ratio （ROR） and Bayesian confidence propagation neural network （BCPNN）. RESULTS A total of 5 726 reports of severe cutaneous adverse reactions were collected， including 3 037 reports for nivolumab，1 465 reports for pembrolizumab， 130 reports for durvalumab， 429 reports for atezolizumab and 665 reports for ipilimumab. All 5 kinds of ICIs caused positive signals， the correlation degree of which was as follows： pembrolizumab＞atezolizumab＞nivolumab＞ipilimumab＞durvalumab. Stevens-Johnson syndrome（SJS） and toxic epidermal necrolysis （TEN） have been reported for all 5 ICIs， and the association was the strongest with pembrolizumab. CONCLUSIONS All 5 kinds of ICIs are associated with the risk of severe skin adverse reactions， and close attention should be paid to their clinical use， especially being cautious when using pembrolizumab. The combination of ICIs should be avoided as much as possible.

Mining and analysis of lorlatinib-induced adverse drug event signals / 中国药房

OBJECTIVE To provide references for the safe use of lorlatinib in clinical practice. METHODS The reporting odds ratio （ROR） method， Medicines and Healthcare Products Regulatory Agency comprehensive standard method （referred to as “MHRA method”） and the Bayesian confidence propagation neural network （BCPNN） method were used to detect adverse drug events （ADEs） signals of lorlatinib in the FDA Adverse Event Reporting System from the first quarter of 2019 to the fourth quarter of 2022. RESULTS & CONCLUSIONS Totally 114 overlapping ADEs signals of lorlatinib were detected by the three methods， among which there were 73 new suspicious ADEs signals which were not covered in the instruction of lorlatinib. When using loratinib in clinical practice， special attention should be paid to ADEs with a high number of cases and signals， such as various neurological diseases， psychiatric diseases， respiratory system， thoracic and mediastinal diseases； clinical manifestations included cerebral edema， cerebral infarction， pulmonary hypertension， mutism， decreased sexual desire， pleural effusion. The signals of mobile thrombophlebitis， radiation necrosis， mutism， vesicoureteral reflux not mentioned in the instructions were all strong in BCPNN detection with high specificity， to which we should pay attention in clinical application.

Myocardial protection using del Nido cardioplegia solution in severe valvular surgery / 中国医师杂志

Objective:To discuss the safety and effectiveness of del Nido cardioplegia solution in severe valvular surgery.Methods:A retrospective analysis of 138 patients of severe valvular disease underwent valve replacement or valvuloplasty in Hunan Provincial People′s Hospital between July 2019 and December 2020 was performed. According to the different cardioplegic solution used, patients were separated in two groups: the del Nido cardioplegia group (D group, n=73) and the St. Thomas cardioplegia group (C group, n=65). The perioperative clinical results of the two groups were compared to evaluate the safety and effectiveness of del Nido cardioplegia in the operation of severe valvular disease. Results:Preoperative characteristics were similar between the two groups, including gender, age, body weight, ejection fraction, and myocardial markers ( P>0.05). No statistical differences were noted in cardiopulmonary bypass time, clamp time, mechanical ventilation time, vasoactive drug use time, ICU and hospital stay time, and ejection fraction before discharge ( P>0.05). However, the times of cardioplegia perfusion [(1.33±0.47)times vs (4.08±0.48)times] and the total perfusion time [(3.96±1.41)min vs (13.15±1.46)min] in group D were lower than those in group C, while the automatic rebound rate (90.41% vs 76.92%) was higher than that in group C ( P<0.05). Both groups successfully completed the operation. There were no serious complications of important organs such as low cardiac output, brain, liver and kidney during and after the operation. There were no deaths during hospitalization, and all patients were cured and discharged. Conclusions:There was no significant difference in myocardial protection between del Nido and St. Thomas cardioplegia solution in severe valvular surgery. The application of del Nido cardioplegia could reduce the frequency of perfusions and total perfusion time.

Effect of mogroside VI on acute liver injury induced by sepsis in mice and related mechanisms / 中国当代儿科杂志

OBJECTIVE@#To study the effect of mogroside VI (MVI) on acute liver injury induced by sepsis in mice and its possible mechanisms. Methods A total of 60 male C57BL/6 mice were randomly divided into five groups: sham-operation, model, low-dose MVI (25 mg/kg), high-dose MVI (100 mg/kg), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) inhibitor (100 mg/kg MVI+30 mg/kg PGC-1α inhibitor SR-18292), with 12 mice in each group. Cecal ligation and puncture were performed to establish a mouse model of sepsis. The drugs were given by intraperitoneal injection after the model was established, once a day for 3 consecutive days. ELISA was used to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Colorimetry was used to measure the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in liver tissue. Hematoxylin-eosin staining was used to observe liver histopathological changes. Liver mitochondrial respiratory function was measured, and mitochondrial respiratory control rate was calculated. RT-PCR was used to measure the copy number of mitochondrial DNA (mtDNA) in liver tissue and the mRNA expression levels of PGC-1α, nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) in liver tissue. Western blot was used to measure the protein expression levels of PGC-1α, NRF-1, and TFAM in liver tissue.@*RESULTS@#Compared with the sham-operation group, the model group had significant increases in the serum levels of ALT and AST and the content of MDA in liver tissue (P0.05). The PGC-1α inhibitor SR-18292 significantly inhibited the intervention effect of high-dose MVI (P<0.05).@*CONCLUSIONS@#MVI can effectively alleviate acute liver injury caused by sepsis in mice, possibly by enhancing mitochondrial biosynthesis mediated by PGC-1α.

Predictive value of red blood cell distribution width for acute kidney injury in children with sepsis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical value of red blood cell distribution width (RDW) in the early prediction of acute kidney injury (AKI) in children with sepsis.</p><p><b>METHODS</b>A total of 126 children with sepsis were divided into an AKI group (n=66) and a non-AKI group (n=60) according to the presence or absence of AKI. These patients were also classified into high-RDW and low-RDW groups according to the mean RDW. The groups were compared in terms of age, male-to-female ratio, body mass index (BMI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, serum blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), serum C-reactive protein (CRP), and routine blood test results. Independent factors associated with RDW were analyzed by multiple linear regression.</p><p><b>RESULTS</b>Age, male-to-female ratio, BMI, CRP, SOFA score, and APACHE II score did not differ significantly between the AKI and non-AKI groups (P>0.05), but the AKI group had significantly higher BUN, Cr, UA, and RDW levels than the non-AKI group (P<0.05). Age, male-to-female ratio, and BMI did not differ significantly between the high-RDW and low-RDW groups (P>0.05), but the high-RDW group had significantly higher BUN, Cr, UA, CRP, SOFA score, APACHE II score, Hb, and mean corpuscular volume (MCV) than the low-RDW group (P<0.05). The multiple linear regression analysis showed that age, sex, APACHE II score, Cr, Hb, and MCV were independent factors associated with RDW.</p><p><b>CONCLUSIONS</b>RDW has a certain clinical value in the early prediction of AKI in children with sepsis.</p>

Correcting false-positive pathogenic categorization of benign variants by re-sequencing of the recessive deafness genes in carriers / 上海交通大学学报（医学版）

Objective· To correct the false-positive categorization of the rare and benign variants by re-sequencing of the recessive deafness genes in carriers. Methods · Heterozygous carriers of known causative mutations in recessive deafness genes were identified from normal hearing relatives of the deaf probands.Targeted next-generation sequencing was performed in those carriers to identify additional variants in trans,which was presumed to be benign. Results · A total of 30 normal-hearing carriers of heterozygous and known pathogenic mutations were identified. By targeted next-generation sequencing of corresponding genes,32 non-synonymous variants in trans were identified,which were categorized to benign mutations under the recessive and full-penetrant mode.Among those variants p.A434T in SLC26A4,p.R266Q in LOXHD1,p.K96Q in MYO15A,p.T123N in GJB2 and pV1299I in CDH23 were five rare variants with minor allele frequency of less than 0.005.Some of the 5 variants were predicted to be pathogenic by prediction programs including Polyphen-2, PROVEAN, SIFT and MutationTaster, or documented to be pathogenic by Deafness Variation Database or Human Genome Mutation Database. Conclusion · Re-sequencing of the recessive deafness genes in carriers may efficiently correct the false-positive categorization of some rare and benign variants to improve the accuracy and efficiency of the next-generation sequencing in diagnosis of monogenic recessive hereditary disorders.

Prevalence and risk factors of stroke：findings from a community in Shenzhen, China / 国际脑血管病杂志

Objective To explore the prevalence and risk factors of stroke in a population over 40 years in a community in Shenzhen, China. Methods The subjects investigated were a population ≥40 years old in this cross-sectional study. Cluster sampling method was used to conduct the unified questionnaires, physical examination, and laboratory examination in the community residents, and then the survey data were used for online entry analysis. Results A total of 5 308 community residents were screened, and 160 experienced stroke. The crude prevalence of stroke was 3 014. 32/100 000. The prevalence of stroke increased with age, and that in males was significantly higher than that in females (3 721. 37/100 000 vs. 2 552. 93/100 000; χ2 = 5. 923, P = 0. 015). There were significant differences in the proportions of males, obvious overweight, hypertension, diabetes mellitus, atrial fibrillation, lack of physical activity, and family history of stroke, as well as age, systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and fasting glucose level between the stroke population and the non-stroke population (all P 80 years) in both males and females. The proportions of diabetes (P < 0. 001) and atrial fibrillation (P < 0. 001) in males, and obvious overweight (P = 0. 001) in females were gradually increased with age, and the proportion of smoking in males weas gradually reduced with age. The proportions of hypertension (P < 0. 001) and obvious overweight (P < 0. 001) in males were significantly higher than those in females at the age of 40 to 49 years. The proportions of hypertension (P < 0. 001), diabetes (P < 0. 001) and obvious overweight (P < 0. 001) in males were significantly higher than those in females at the age of 50 to 59 years. The proportion of hypertension in males was significantly higher than that in females at the age of 60 to 69 years (P = 0. 039). The proportions of hypertension (P = 0. 016), atrial fibrillation (P = 0. 028) and hyperlipidemia (P = 0. 023) in females were significantly higher than those in males at the age of 70 to 79 years. The proportion of obvious overweight in females was significantly higher than that in males at the age of ≥80 years (P =0. 001). Conclusions The crude prevalence of stroke is higher among the community residents. The the levels of exposure to stroke risk factors including hypertension, diabetes and atrial fibrillation are higher. It may be important to intervene on these risk factors in community residents, especially in elders and those with family history of stroke.

Efficacy and Safety of Pituitrin Combined with Phentolamine versus Pituitrin Alone in the Treatment of Bron-chiectasis Hemoptysis:A Systematic Review / 中国药房

OBJECTIVE:To systematically review the efficacy and safety of pituitrin combined with phentolamine versus pitui-trin alone in the treatment of bronchiectasis hemoptysis(BH),and provide evidence-based reference for the clinical treatment. METHODS:Retrieved from PubMed,Cochrane Library,EMBase,CJFD,Wanfang and VIP database,the randomized controlled trails(RCT)about pituitrin combined with phentolamine(test group)versus pituitrin alone(control group)in the treatment of BH were collected,and afterdata extract and quality evaluation ,Meta-analysis was performed by using Rev Man 5.2.3 statistics soft-ware. RESULTS:A total of 43 RCTs were included,involving 3 094 patients. Results of Meta-analysis showed the significant effi-cacy [RR=1.50,95%CI(1.38,1.62),P<0.001] and effective rate [RR=1.25,95%CI(1.20,1.30),P<0.001] in test group were sig-nificantly higher than control group,inefficacy [RR=0.29,95%CI(0.23,0.36),P<0.001], hemoptysis stopped or remission time [MD=-2.00,95%CI(-2.43,-1.57),P<0.001],incidence of headache [RR=0.36,95%CI(0.22,0.59),P<0.001],incidence of chest tightness [RR=0.41,95%CI(0.26,0.63),P<0.001],incidence of abdominal pain [RR=0.26,95%CI(0.16,0.43),P<0.001] and incidence of elevated blood pressure [RR=0.28,95%CI(0.14,0.56),P<0.001] in test group were significantly lower than control group,there were significant differences in 2 groups. CONCLUSIONS:Pituitrin combined with phentolamine has better efficacy and safety than pituitrin alone in the treatment of BH. Due to the limit of methodological quality and sample size,it re-mains to be further verified with more rigorously designed and long-term follow-up of large-scale RCT.

Association of OPG gene single nucleotide polymorphisms with susceptibil-ity to rheumatoid arthritis in Chinese Han population / 中国病理生理杂志

AIM: To investigate the association of osteoprotegerin ( OPG) gene single nucleotide polymor-phisms (SNPs), 163A/G (rs3102735) and 245T/G (rs3134069), with susceptibility to rheumatoid arthritis (RA) in Chinese Han population .METHODS:A total of 205 patients with RA and 171 healthy control subjects were enrolled into this study.Genotyping was performed by polymerase chain reaction-based restriction fragment length polymorphism and subsequently confirmed by DNA sequencing .Odds ratio ( OR) and 95%confidence intervals ( CI) were calculated for the risk genotypes and alleles .RESULTS: OPG gene polymorphisms 163A/G and 245T/G were conformed to the Hardy-Weinberg equilibrium .The statistical differences in the genotypes of AA , AG and GG at 163A/G locus were found in RA and controls.The G allele was associated with an increased risk of RA , with OR of 1.219 (95%CI:1.066~2.339).No significant difference was observed between RA group and control group with respect to genotypic and allelic frequencies of OPG gene 245T/G (P>0.05).CONCLUSION:The OPG gene 163A/G SNP may be associated with RA susceptibility , and G allele may be the risk factor for developing RA .

Diagnostic value of high mobility group box 1 for acute appendicitis in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the value of high mobility group box 1(HMGB1) in the diagnosis of pediatric acute appendicitis.</p><p><b>METHODS</b>The children with acute abdomen who had a diagnosis of suspected acute appendicitis between January and July 2013 and 25 healthy children were enrolled in this study. Serum HMGB1 levels were measured using ELISA on admission. The patients were classified into 2 groups according to surgery confirmation or pathological results: appendicitis (n=28) and non-appendicitis (n=35).</p><p><b>RESULTS</b>Serum HMGB1 levels and WBC in the appendicitis and non-appendicitis groups were significantly higher than in the healthy children group (P<0.01). The appendicitis group showed more increased serum HMGB1 levels compared with the non-appendicitis group (median: 32.9 ng/mL vs 22.0 ng/mL; P<0.01). For a diagnosis of acute appendicitis, the sensitivity and specificity of serum HMGB1 was 71.4% and 82.9% respectively at the best cutoff of 28.0 ng/mL, with the accuracy of 77.8% and the area under the curve of 0.765 (95%CI 0.638-0.893).</p><p><b>CONCLUSIONS</b>HMGB1 may play a role in the diagnosis of pediatric acute appendicitis.</p>

Study on thymic output function in post-allogeneic hematopoietic stem cell transplantation patients / 白血病·淋巴瘤

Objective To quantify sjTREC using a modified method in patients who underwent allogeneic hematopoietic stem transplantation (all-HSCT),and determine the level of thymic output function and analyse the influencing factors in post-allo-HSCT patients.Methods Real time quantitative PCR was used to detect sjTREC levels from the peripheral blood DNA of pre-transplantation,14 d,28 d,3 m,6 m,9 m,1 y,1.5 y,2 y,2.5 y,and above 2.5 y after HSCT,and analyse thymic output function and related factors after HSCT.sjTREC levels in 24 normal individuals were also determined to use as the normal range.Results The mean of Log (sjTREC copies/ml) in normal individuals was 3.74±0.26.Negative correlation existed between thte Log sjTREC and the age (r =-0.65,P ＜ 0.01).There was no clear association between the TREC and the gender.Log sjTREC in pre-transplantation patients was 3.09±0.52,and the levels of sjTREC in 14 d,28 d,6 m,1 y after HSCT were 1.18±0.22,2.16±0.31,1.31±0.2,1.83±0.31,respectively.There was no significant difference between normal individuals and patients 1.5 years after HSCT.The post-transplantation level of sjTREC was not related to the age,but was negatively correlated to the acute graft versus host disease (aGVHD) 1 year after HSCT.There was no difference between patients with or without aGVHD 1.5 years post-HSCT.Conclusion The modified method for detecting sjTREC is applicable to allo-HSCT.The recovery of thymic output function after allo-HSCT is slow,in which aGVHD may have a negative effect.

Clinical risk factors for capillary leak syndrome in children with sepsis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features of capillary leak syndrome (CLS) in children with sepsis, and to analyze its risk factors.</p><p><b>METHODS</b>Clinical data of 384 children with sepsis was studied retrospectively. They included 304 cases of general sepsis, 54 cases of severe sepsis and 26 cases of septic shock, and were divided into non-CLS (n=356) and CLS groups (n=28). Univariate analysis was performed for each of the following variables: sex, age, malnutrition, anemia, coagulation disorders, white blood cell count, C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, blood glucose, lactic acid, Pediatric Risk of Mortality (PRISM) III score, pediatric critical illness score (PICS), severe sepsis and number of failed organs≥3. The statistically significant variables (as independent variables) were subjected to multivariate logistic regression analysis.</p><p><b>RESULTS</b>The incidence rate of CLS in children with septic shock, severe sepsis and general sepsis were 42.3%, 20.1% and 1.3%, respectively, with significant differences among them (P<0.01). There were significant differences in anemia, coagulation disorders, CRP, PCT>2 ng/mL, TNF, IL-1, IL-6, blood glucose, lactic acid, PRISM III score, PICS and number of failed organs≥3 between the non-CLS and CLS groups (P<0.05). Severe sepsis/shock and PRISM III score were the independent risk factors for CLS in children with sepsis.</p><p><b>CONCLUSIONS</b>The severity of sepsis and PRISM III score are positively correlated with the incidence of CLS in children with sepsis. Early monitoring of such factors as infection markers and blood glucose in children with severe sepsis and high PRISM III score may contribute to early diagnosis and effective intervention, thus reducing the mortality from CLS in children with sepsis.</p>

Efficacy evaluation of high intensity focused ultrasound combined with intra-arterial infusion of gemcitabine in the treatment of pancreatic cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to discuss the clinical effectiveness of high intensity focused ultrasound (HIFU) combined with gemcitabine administered by intra-arterial infusion on intermediate and advanced pancreatic cancer.</p><p><b>METHODS</b>Forty-eight patients with intermediate and advanced pancreatic cancer were divided into two groups. Twenty-four patients of the experimental group were treated by HIFU combined with gemcitabine, and 24 patients of the the HIFU group were treated by HIFU alone. Then the curative effect, extent of pain relief, and survival time were compared in the course of the treatment between the two groups.</p><p><b>RESULTS</b>As compared with those in the control group, the overall response rate, level of pain relief, and 12-month survival rate after therapy were higher and the median survival time was longer in the joint group (P < 0.05).</p><p><b>CONCLUSIONS</b>Ultrasound imaging, CT and associated tumor marker detection can make effective measurement to evaluate curative effect on pancreatic carcinoma. HIFU plus gemcitabine administered by intra-arterial infusion can improve the clinical therapeutic efficacy, pain relief, quality of life and long-term survival rate of patients with pancreatic cancer.</p>

Relationship between uncoupling protein 2 gene promoter-866 G/A polymorphism and Chinese diabetic nephropathy / 中国医师进修杂志

Objective To investigate the relationship between uncoupling protein 2 (UCP-2) gene promoter -866 G/A polymorphism and Chinese diabetic nephropathy (DN). Methods A total of 182 patients with type 2 diabetic mellitus were selected and divided into DN group (90 cases with DN ) and NCD group (92 cases without DN ). Genomic DNA was detected, and UCP-2 genotype and allele gene frequency was confirmed by polymerase chain reaction-restrictive fragment length polymorphism, then compared.Results The genotype frequency of UCP-2 gene promoter-866 G/A polymorphism was distributed in DN group[GG 14.44%( 13/90),GA 31.11%(28/90),AA 54.44%(49/90)],and distributed in NCD group[GG 29.35% ( 27/92 ), GA 32.61% ( 30/92 ), AA 38.04% ( 35/92 )], and there was significant difference between two groups ( χ2 = 7.28 , P ＜ 0.05 ). There was also significant difference in allele gene frequency between DN group and NCD group[G 45.65% (84/184) vs. 30.00% (54/180),A 54.35% (100/184) vs. 70.00% (126/180)]( χ2 = 9.47, P ＜ 0.05 ). Conclusion There is correlation between the UCP-2 gene promoter-866 G/A polymorphism and Chinese DN, and the incidence of DN with A/A genotype is increased.

Isolation and identification of cancer stem cells from primary human ovarian cancer tissues / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To isolate and identify the cancer stem cells from primary human ovarian cancer tissues.</p><p><b>METHODS</b>Fresh tumor tissues from five cases of pathologically diagnosed ovarian cancers were taken, minced and then digested with collagenase and hyaluronidase to obtain single cell suspension. The erythrocytes were removed with ACK Lysis buffer. The suspensions were sorted by magnetic activated cell sorting (MACS) using CD133-binding microbeads. Then the sorted CD133(+) cells were verified by flow cytometry. The cells were cultured in serum-free medium supplemented with EGF, bFGF, insulin and BSA, and grew into spheroids. Immunofluorescence, differentiation and tumor formation tests of the cells were performed to characterize the properties of cancer stem cells.</p><p><b>RESULTS</b>The ovarian cancer stem cells were successfully isolated from primary human ovarian tumors, which formed typical spheroids in serum-free medium and had stronger ability of tumorigenesis. The results of related experiments verified that CD133 positive cells owned the properties of cancer stem cells.</p><p><b>CONCLUSIONS</b>The ovarian cancer stem cells presenting the characteristics of stemness in vitro and in vivo, have been successfully isolated from primary human ovarian tumor tissues by MACS. The isolated ovarian cancer stem cells could be used in future researches of their biological functions.</p>

Development of early human fetal testes after xenografting into mice / 解剖学报

Objective To investigate the developmental feasibility of early human fetal testes (<3 months) using xenografting technique and to acquire an accessible donor derivation that is essential for studying human germ cell development. Methods Nine testes from 10-13 weeks aborted fetus were grafted under the back skin of 6 castrated nude mice. Grafts were collected at different time point according to the growth of the donor tissues and the health condition of the recipients. Morphological and histological analyses were performed for the observation of the development of grafted immature testicular tissues. Results The mass of grafts was increased from about 5-7mg to 84.1mg (the biggest). Six of 9 testes were to be in developing. Histological observations showed a significant expansion of seminiferous tubules from (44.26±3.14)μm to (77.69±7.47)μm. Cells dispersedly distributed in seminiferous cords at the time of grafting migrated towards the basal part of seminiferous epithelium. Some germ cells with spermatogonium-like characteristics located on the basement membrane. Sertoli cells were in stages from immature into matured with abundant cytoplasm which were orderly arranged around spermatogonia forming a niche-like structure. Conclusion Testes from early aborted human fetus grafted under the back skin of castrated nude mice showed further development and therefore could be used as an easier accessible donor tissues for the investigation of human spermatogenetic mechanism.

Establishment and clinical application of fluorescent polymerase chain reaction for the determination of-88/-123 polymorphisms in the Myxovirus resistance protein A gene promoter / 中华传染病杂志

Objective To establish a fluorescent polymerase chain reaction (PCR) method for rapid, sensitive and specific determination of -88/-123 polymorphisms in Myxovirus resistance protein A (MxA) gene promoter so as to provide molecular biology tool for optimized interferon-a treatment in chronic hepatitis B patients. Methods Hepatitis B virus (HBV) genotyping,serum HBV DNA level,and- 88/- 123 polymorphisms in MxA gene promoter of patients who had been treated with interferon-α were detected. The statistical analysis was done by using SPSS software to understand the relationship between MxA gene polymorphisms and interferon-α treatment. Afterwards, an optimal fluorescent PCR system was established to determine -88/-123 polymorphisms in MxA gene promoter. The sensitivity and the specificity of this system were confirmed by DNA sequencing. P-value of chi square test, odds ratios of regression analysis and 95% confidence intervals were employed. Results Patients with- 88 G/T and - 123 C/A in the interferon-stimulated response element in MxA gene promoter were interferon-α sensitive, while patients with - 88 GIG and - 123 C/C were not interferon-α sensitive. The coincidence rate of this system was 99.65% in comparison with DNA sequencing.Conclusion MxA gene polymorphisms could be rapidly and sensitively determined by this fluorescent PCR system.

A study on HLA-DQB1 allele associated with genetic susceptibility to duodenal ulcer in Guangdong Hans / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the genetic susceptibility of HLA-DQB1 alleles to duodenal ulcer in Chinese Hans from Guangdong area around.</p><p><b>METHODS</b>Hundred and five patients with duodenal ulcer and hundred and five healthy controls were examined for HLA-DQB1 genotypes. HLA-DQB1 allele typing was carried out by polymerase chain reaction with sequence specific primers (PCR-SSP).</p><p><b>RESULTS</b>The allele frequency of HLA-DQB1*0602 in patients with duodenal ulcer (64.8%) was significantly higher than that in healthy controls (14.3%).</p><p><b>CONCLUSION</b>These findings suggest that HLA-DQB1*0602 is a susceptible gene to duodenal ulcer in Guangdong Hans of China. And at HLA-DQB1 site, there are immunogenetic differences between duodenal ulcer patients and healthy controls.</p>

Conversion of human umbilical cord blood-derived cells into hepatocyte-like cells in a culture system mimicking hepatic injury / 北京大学学报(医学版)

Objective:To explore the effect of the microenvironment induced by damaged mouse hepatic cells on the conversion of human umbilical cord blood-derived cells into hepatocyte-like cells. Methods: A hepatic injury-like microenvironment was mimicked using carbon tetrachloride damaged mouse hepatic cells, where mononuclear cells (MNC) from human umbilical cord blood were cultured in a compartment separated by trans-well membrane. Histochemical staining, reversed transcription-polymerase chain reaction (RT-PCR) and gene sequencing were performed for the information on the conversion of human umbilical cord blood MNC. Results: A number of PAS positive stained cells in MNC co-cultured with damaged mouse hepatic cells were observed after 72 h. Cells expressing mature hepatocyte markers, human albumin (hALB) and human GATA-4 (hGATA-4) mRNA were detected by RT-PCR, which was further confirmed with sequencing. Relevant control groups, MNC co-cultured with normal mouse hepatic cells and MNC cultured alone remained negative. Conclusion: The culture system using damaged mouse hepatic cells as stimulator could be a potential in vitro system for the conversion of human umbilical cord blood-derived cells into hepatocyte-like cells.