Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

PRKCDBP Methylation is a Potential and Promising Candidate Biomarker for Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#The occurrence and development of lung cancer are closely linked to epigenetic modification. Abnormal DNA methylation in the CpG island region of genes has been found in many cancers. Protein kinase C delta binding protein (PRKCDBP) is a potential tumor suppressor and its epigenetic changes are found in many human malignancies. This study investigated the possibility of PRKCDBP methylation as a potential biomarker for non-small cell lung cancer (NSCLC).@*METHODS@#We measured the methylation levels of PRKCDBP in the three groups of NSCLC tissues. Promoter activity was measured by the dual luciferase assay, with 5'-aza-deoxycytidine to examine the effect of demethylation on the expression level of PRKCDBP.@*RESULTS@#The methylation levels of PRKCDBP in tumor tissues and 3 cm para-tumor were higher than those of distant (>10 cm) non-tumor tissues. Receiver operating characteristic (ROC) curve analysis between tumor tissues and distant non-tumor tissues showed that the area under the line (AUC) was 0.717. Dual luciferase experiment confirmed that the promoter region was able to promote gene expression. Meanwhile, in vitro methylation of the fragment (PRKCDBP_Me) could significantly reduce the promoter activity of the fragment. Demethylation of 5'-aza-deoxycytidine in lung cancer cell lines A549 and H1299 showed a significant up-regulation of PRKCDBP mRNA levels.@*CONCLUSIONS@#PRKCDBP methylation is a potential and promising candidate biomarker for non-small cell lung cancer.

Association of CYP2C19 and CYP3A5 gene polymorphisms with myocardial infarction / 中华医学遗传学杂志

OBJECTIVE@#To assess the association of CYP2C19 and CYP3A5 gene polymorphisms with the risk of myocardial infarction.@*METHODS@#Five hundred patients with myocardial infarction and 500 healthy controls were randomly selected. Fluorescent PCR and Sanger sequencing were used to detect the CYP2C19 and CYP3A5 gene polymorphisms. Logistic regression was used to analyze the correlation between the polymorphisms and myocardial infarction. Quanto software was used to evaluate the statistical power.@*RESULTS@#The two groups had significant difference in the frequency of AG, GG genotypes and A allele of the CYP2C19 gene rs4986893 locus and the AA, AG, GG genotypes and G allele of the CYP3A5 gene rs776746 locus ( P<0.05), but not in the frequency of genotypes and alleles of CYP2C19 gene rs4244285 and rs12248560 loci, and the AA genotype of the rs4986893 locus. After correction for age, gender, and body mass index, Logistic regression indicated that the AG genotype and A allele of the CYP2C19 gene rs4986893 locus, and the GG genotype and G allele of CYP3A5 gene rs776746 locus are associated with susceptibility of myocardial infarction, while rs4986893 GG genotype and AA and AG genotypes of rs776746 may confer a protective effect. Based on the sample size and allele frequency, analysis with Quanto software suggested that the result of this study has a statistical power of 99%.@*CONCLUSION@#CYP2C19 and CYP3A5 gene polymorphisms may increase the risk for myocardial infarction.

Efficacy of triangular mechanical reconstruction for treatment of failed fixation of intertrochanteric factures / 中华创伤杂志

Objective:To investigate the curative effect of triangular mechanical reconstruction in revision of failed fixation of intertrochanteric factures.Methods:A retrospective case series study was conducted for data of 11 patients with failed treatment of intertrochanteric fractures treated at First Medical Centre, Chinese PLA General Hospital from January 2017 to December 2019, including 7 males and 4 females, aged 41-75 years [(57.9±11.4)years]. The patients underwent revision surgery to achieve mechanical reconstruction of the proximal femoral triangular structure by two different implants. Among them, 6 patients were fixed using the dynamic condylar screw (DCS) combined with anteromedial plate and 5 patients were fixed using the cephalomedullary nail combined with anteromedial plate. The fracture healing rate and time, neck-shaft angle, neck anteversion angle and complications were detected. The lower extremity functional scale (LEFS), short form 12 health survey questionnaire (SF-12) and pain visual analogue scale (VAS) were measured at postoperative 6 and 12 months to evaluate functional recovery and quality of life.Results:All patients were followed up for 12-45 months [(19.1±10.8)months]. The fracture healing rate was 100%, with the healing time of 3-8 months [(4.7±1.8)months]. Compared with the unaffected limb, the neck-shaft angle and neck anteversion angle of the affected side were reduced ( P>0.05), and no secondary fracture reduction loss occurred before healing ( P>0.05). There were no postoperative complications such as femoral head avascular necrosis and implant failure. The LEFS score was (44.7±8.2)points at postoperative 12 months, significantly improved compared with that at postoperative 6 months [(61.6±10.4)points] ( P<0.05). The VAS was 1.5 (0, 2)points at postoperative 12 months, significantly decreased compared with that at postoperative 6 months [3.5(2, 4)points] ( P<0.05). The SF-12 score in physical state [(42.5±9.0)points] and mental state [(55.7±5.7)points] were also significantly improved compared with those at postoperative 6 months [(30.0±6.4)points, (43.6±6.2)points] ( P<0.05). Conclusions:Based on the characteristics of structural mechanics of the proximal femur, the DCS or cephalomedullary nail combined with anteromedial plate used to construct a triangular stable structure can achieve stable fracture reduction and maintenance reduction, relieve pain and improve function recovery as well as quality of life. This may provide an optimized revision strategy for failed fixation of intertrochanteric fractures.

Comparative analysis of chemical compositions of fruits of Perilla frutescens var. arguta and P. frutescens var. frutescens by pre-column derivatization with GC-MS / 中国中药杂志

The present study compared the appearance and chemical composition of fruits of Perilla frutescens var. arguta(PFA) and P. frutescens var. frutescens(PFF). VHX-6000 3 D depth of field synthesis technology was applied for the appearance observation. The metabolites were qualitatively and quantitatively analyzed by pre-column derivatization combined with gas chromatography-mass spectrometry(GC-MS). Finally, cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least-squares discriminant analysis(OPLS-DA) were applied for exploring the differences in their chemical compositions. The results indicated that the size and color of PFA and PFF fruits were different. PFF fruits were significantly larger than PFA fruits. The surface color of PFA fruits was brown, while PFF fruits were in multiple colors, such as white, grayish-white, and brown. Amino acids, saccharides, organic acids, fatty acids, and phenolic acids were identified in PFA and PFF fruits. The results of CA, PCA, and OPLS-DA indicated significant differences in the content of components between PFA and PFF fruits. Three metabolites, including D-glucose, rosmarinic acid, and D-fructose, which were significantly higher in PFA fruits than in PFF fruits, were screened out as differential metabolites. Considering the regulation on the content of rosmarinic acid in Perillae Fructus in the Chinese Pharmacopoeia(2020 edition), the medicinal value of PFA fruits is higher than that of PFF. In conclusion, there are differences in appearance and chemical composition between PFA fruits and PFF fruits. These results are expected to provide fundamental data for specifying plant source and quality control of Perillae Fructus.

Research advances of chemokine receptor CX3CR1 and microglia in retinal degenerative diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration are the main clinical blinding eye diseases with complex etiology and irreversible damage to vision. CX3CR1 is a specific receptor of the chemokine CX3CL1. Both of them participate in various physiological functions and pathological changes of the whole body through regulating the immune system of the body. In recent years, studies have pointed out that CX3CR1 regulates the activity and function of retinal microglia, which play an important role in the process of retinal degenerative diseases. In this paper, the structure and function of the chemokine receptor CX3CR1 and the role of microglia in retinal degenerative diseases were reviewed, so as to provide ideas and directions for future research and treatment of such diseases.

Mechanism of microRAN-145 on proliferation and apoptosis of breast cancer cell line MCF-7 / 解剖学报

Objective To explore the mechanism of microRNA-145 (miR-145) involved in proliferation and apoptosis of breast cancer MCF-7 cells. Methods The immortalized breast cancer cell line MCF-7 cells were cultured in vitro and transfected with miR-145. Real-time PCR and Western blotting were used to detect mRNA and protein levels, respectively. The proliferation level of each group was detected by cell counting kit-8 (CCK-8) method , and the apoptosis level of MCF-7 cells in different treatment groups was detected by flow cytometer. Results Real-time PCR result showed that miR-145 did not affect Caspase-3, proliferating cell nuclear antigen (PCNA) and B cell lymphoma factor 2 (Bcl-2) mRNA levels in MCF-7 cells. Western blotting analysis showed that compared with the control group, transfection of miR-145 for 96 hours significantly increased the expression of Caspase-3 and inhibited the expression of PCNA and Bcl-2. The result of CCK-8 assay showed that the proliferation rate of MCF-7 cells was decreased after overexpression of miR-145 for 72 hours and 96 hours (P<0. 05). The result of flow cytometer showed that the apoptosis rate of MCF-7 cells in overexpression group was significantly higher than that in the control group (P<0. 05). Conclusion MiR-145 can inhibit the proliferation and promote the apoptosis of MCF-7 cells by down-regulating PCNA and Bcl-2 and up-regulating the expression of Caspase-3, which may be a new target for breast cancer treatment.

Application of holographic image navigation in urological laparoscopic and robotic surgery / 中华泌尿外科杂志

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

Research on all-dimensional health care model of military cadres based on health big data / 医学研究生学报

With the widespread application of modern information technologies such as the Internet of Things, cloud computing, block chain, and artificial intelligence, the integration of multidisciplinary key technologies and health big data will vigorously promote the development of health causes and health industries. To construct a new comprehensive health care model of all staff, all area, whole process and full-time service according to the real needs of retired military cadres, we integrated several information technologies such as the Internet of Things, cloud computing, block chain and artificial intelligence, and strengthened the collection, mining, analysis and utilization of big data technology in the all-dimensional health care model. Four kinds of health care models and their corresponding operating mechanisms were constructed. With better practicability and promotion value, our new models can effectively improve the quality of prevention, medical treatment and health care in primary health institutions.

Design mentality of establishing performance distribution system based on homogeneous subsidy base / 医学研究生学报

Performance management is a key direction of the reform of the national medical and health system, and it is also an important starting point for promoting the development of hospital connotation. In view of the contradiction among the current hospital performance distribution system, this paper proposes a design mentality of performance distribution system based on homogenization subsidy base, and expounds the basic connotation and cognitive basis of homogenization subsidy base. The key elements of the design of the performance distribution system are discussed from four aspects: pre-adjusted total control, coefficientized personnel attendance, same performance appraisal, and homogenization subsidy base. At the same time, this paper also analyzes the characteristics of the performance distribution system based on the homogenization subsidy base. The application prospects of the performance distribution system are prospected from three aspects: the national medical reform requirements, the discipline development discipline and the system's own characteristics.

Clinical significance of plasma D-dimer level in dermatomyositis / 中国实用内科杂志

OBJECTIVE: To analyze the clinical significance of plasma D-dimer levels in dermatomyositis(DM). METHODS: The correlations between D-dimer level and important clinical indicators of DM patients were analyzed by assessing the plasma D-dimer level in 46 patients with DM(among which 17 cases were amyopathic dermatomyositis)and 22 cases of PM. The clinical significance of D-dimer level in DM patients with interstitial lung disease(ILD)was also analyzed. RESULTS: The D-dimer level(1.18±1.17μg/L)in DM group was significantly higher than that(0.61±0.43μg/L)in PM group(P=0.03).In DM group, D-dimer level was positively correlated with lactate dehydrogenase(R=0.402,P=0.01),erythrocyte sedimentation rate(R=0.337,P=0.03)and C-reactive protein level(R=0.404,P=0.01).Our results also showed that the D-D level in DM group was negatively correlated with peripheral blood lymphocyte count(R=-0.392,P=0.01), peripheral blood CD3+T(R=-0.360,P=0.03)and CD3+CD8+Tlymphocyte count(R=-0.342,P=0.04).There was no significant difference in D-dimer levels between patients with ILD and those without ILD. Conclution Increased plasma of D-D may be an important indicator of disease activity in DM.

B cell activating factor profiles in cerebrospinal fluid in patients with lupus encephalopathy / 中国实用内科杂志

OBJECTIVE: To detect the levels of B cell activating factor(BAFF) in cerebrospinal fluid(CSF) in patients with lupus encephalopathy(LE). METHODS: CSF from 15 patients with LE and 11 controls with headache were collected. The controls with headache were excluded diseases at last and used to be controls. The levels of BAFF were measured by enzyme-linked immunosorbent assay(ELISA). Clinical features and laboratory data were collected from the patients with LE. RESULTS: The levels of BAFF in the CSF of patients with LE were significantly higher than that of controls [(1421.3±670.31) pg/mL vs.(21.9±21.44) pg/mL, P<0.01]. The levels were also increased significantly when compared with paired sera[(1011.4±356.43) ng/L, P<0.05]. CONCLUSION: was not found between the levels of BAFF and serum BAFF as well as the other clinical items. CONCLUSION: Brain immunity may contribute the increased BAFF in CSF in patients with LE.

Lower clearance of sodium tanshinone IIA sulfonate in coronary heart disease patients and the effect of total bilirubin: a population pharmacokinetics analysis / 中国天然药物

This study developed a population pharmacokinetic model for sodium tanshinone IIA sulfonate (STS) in healthy volunteers and coronary heart disease (CHD) patients in order to identify significant covariates for the pharmacokinetics of STS. Blood samples were obtained by intense sampling approach from 10 healthy volunteers and sparse sampling from 25 CHD patients, and a population pharmacokinetic analysis was performed by nonlinear mixed-effect modeling. The final model was evaluated by bootstrap and visual predictive check. A total of 230 plasma concentrations were included, 137 from healthy volunteers and 93 from CHD patients. It was a two-compartment model with first-order elimination. The typical value of the apparent clearance (CL) of STS in CHD patients with total bilirubin (TBIL) level of 10 μmol(L was 48.7 L(h with inter individual variability of 27.4%, whereas that in healthy volunteers with the same TBIL level was 63.1 L(h. Residual variability was described by a proportional error model and estimated at 5.2%. The CL of STS in CHD patients was lower than that in healthy volunteers and decreased when TBIL levels increased. The bootstrap and visual predictive check confirmed the stability and validity of the final model. These results suggested that STS dosage adjustment might be considered based on TBIL levels in CHD patients.

Screening of MYH7 gene mutation sites in hypertrophic cardiomyopathy and its significance / 中华医学杂志(英文版)

BACKGROUND@#There have been few reports of mutations in the beta-myosin heavy chain (MYH7) gene in hypertrophic cardiomyopathy (HCM), which is associated with sudden cardiac death caused by HCM. This study aimed to screen the mutation sites in the sarcomeric gene MYH7 in Chinese patients with HCM. We also planned to analyze the pathogenicity of the mutation site as well as its significance in clinical and forensic medicine.@*METHODS@#From January 2006 to June 2017, autopsy cases were collected from the Department of Pathology, the Affiliated Hospital of Qingdao University. The experiment was to detect MYH7 gene status in formalin-fixed paraffin-embedded tissues from 18 independent autopsy cases who suffered HCM related sudden death (fatal HCM) and 20 cases without cardiomyopathy. Common mutation exon fragments of MYH7 gene were amplified by polymerase chain reaction. The end-of-deoxygenation method and gene cloning method were further performed to analyze the mutation sites. Homologous comparison among mutant sites was conducted using BLAST online database.@*RESULTS@#The 1336th nucleotide of MYH7 gene at exon 14 was converted from T to G in one HCM case, resulting in the conversion of threonine (Thr) at position 446 to proline (Pro). In another case, the 1402th nucleotide at exon 14 was converted from T to C, resulting in the conversion of phenylalanine (Phe) at position 468 to leucine (Leu). Homologous comparison results showed that the two amino acid residues of Thr446 and Phe468 are highly conserved among different species.@*CONCLUSIONS@#Our results showed fatal HCM harbored mutations of Thr446Pro and Phe468Leu in the MYH7 gene. It is significant for clinical and forensic medicine to further explore the functions and detailed mechanisms of these mutations.

Clinical Effect of Wandaitang on Endometrial Carcinoma After Operation / 中国实验方剂学杂志

Objective:To observe the effect of syndrome differentiation and treatment with Wandaitang on symptoms, quality of life and function of immunologic after operation of endometrial carcinoma (EC), in order to discuss the mechanism of action according to regulation of microenvironment of EC. Method:The 109 patients were divided into control group (54 cases) and observation group (55 cases) by random number table. Patients in control group got radiotherapy and/or chemotherapy according to different stages after operation. Patients in observation group were additionally given syndrome differentiation and treatment with Wandaitang, 1 dose/day. And a course of treatment was 3 months. Before and after treatment, symptoms, sign, functional assessment of cancer therapy-general (FACT-G) were scored. And levels of T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+), natural killer cell (NK), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), insulin-like growth factor-1(IGF-1), interleukin-17 (IL-17) and IL-10 were detected. Result:After treatment, the scores of symptoms, signs and total scores of the patients in the observation group were lower than the control group (PP+, CD4 + and CD4 +/CD8 + in the observation group were higher than those in the control group(PPβ, IGF-1, IL-17 and IL-10 in the observation group were lower than those in the control group. Conclusion:Wandaitang can ameliorate clinical symptoms, improve quality of life of patients and immune function of organism, regulate multiple cytokines, change the tumor microenvironment of endometrial carcinoma.

Ampelopsin inhibited apoptosis and migration of SMMC-7721 cells through MAPKs signaling pathway / 药学学报

This research is aimed to investigate the effect of ampelopsin on apoptosis and migration of human hepatoma SMMC-7721 cells and explore the molecular mechanism. SMMC-7721 cells were pretreated with different doses of ampelopsin and cells proliferation was detected by CCK8 kit. Cell morphology was observed under an inverted microscope. Nuclear morphology was detected by DAPI staining. Apoptotic rate was detected by Annexin V-FITC/PI flow cytometry. Migration and invasion were detected by Transwell and scratch healing test. Western blotting was used to detect cleavage of poly ADP-ribose polymerase (PARP), expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), E-cadherin, and N-cadherin, and phosphorylation of ERK, P38 and JNK in MAPKs pathway. Our results showed that ampelopsin significantly inhibited proliferation and induced apoptosis of SMMC-7721 cells, with half inhibition dose (IC50) for 24 h was 38.98 μg·mL-1. With 50 μg·mL-1 ampelopsin treatment, typical apoptotic morphological changes occurred, such as cell detachment, shrinkage and nuclear condensation. Apoptotic rate increased from 15% to 55.1%, with PARP cleavage significantly increased. In addition, treatment of ampelopsin reduced scratch healing of cells and transmembrane cells number. The expression levels of MMP-2 and MMP-9 were decreased. Further analysis of EMT-related proteins showed that after ampelopsin treatment, E-cadherin was up-regulated and N-cadherin was down-regulated. During ampelopsin treatment, ERK reached its peak of activation after 1 h, while the maximum activation time of JNK was 12 h. Meanwhile, P38 was activated within 4 h, with the highest point at 2 h. But after 4 h, ampelopsin inhibited phosphorylation of P38. These results indicated that ampelopsin induced apoptosis and reduced migration through activating MAPKs pathway and reversing EMT process in SMMC-7721 cells. This work provides a mechanistic basis for utilizing ampelopsin for anti-hepatocarcinoma treatment.

The efficacy and safety of BCG in the prevention of postoperative recurrence of intermediate and high-risk non-muscle invasive bladder cancer: a randomized, controlled, multi-center clinical trial (mid-term report) / 中华泌尿外科杂志

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.

Association of Cytokines with Alanine Aminotransferase, Hepatitis B Virus Surface Antigen and Hepatitis B Envelope Antigen Levels in Chronic Hepatitis B / 中华医学杂志(英文版)

Background@#Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB).@*Methods@#Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis.@*Results@#IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = -0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = -2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ = 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = -1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ = 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = -0.358, t = -2.308, P = 0.024), HBsAg (β = -0.359, t = -2.288, P = 0.025), and HBeAg contents (β = -0.355, t = -2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = -0.459, t = -4.225, P = 0.000; β = -0.616, t = -6.334, P = 0.000; and β = -0.290, t = -2.433, P = 0.018; respectively).@*Conclusions@#IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.

Reversal Effect and Mechanism of 15-PGHD Induction Drugs on the Multidrug Resistance of Human Breast Cancer Cell Line MCF-7/ADR / 中国药学杂志

OBJECTIVE: To examine the expression of 15-hydroxyprostaglandin dehydrogenase(15-PGDH) in human multidrug-resistant breast cancer line MCF-7/ADR and to explore the reversal effect and mechanism of 15-PGHD induction drugs on MCF-7/ADR cells. METHODS: The RT-PCR and Western blot were used to detect 15-PGDH, COX-2 mRNA and protein expression in MCF-7 and MCF-7/ADR cells. PGE2 levels in supernatant of cells were determined by ELISA assay. Anti-proliferation effect and chemotherapy sensitivity to ADM of 15-PGDH induction drugs (indomethacin, ibuprofen and pioglitazone, dexamethasone) on breast cancer cells were assayed by MTT method. Cell apoptosis was detected by Hochest 33258 stain assay. RESULTS: Compared with MCF-7 cells, the 15-PGDH expression was significantly decreased, COX-2 expression was significantly increased and PGE2 levels in cell supernatant were increased in MCF-7/ADR cells. 15-PGDH induction drugs (indomethacin, ibuprofen and pioglitazone, dexamethasone) increased 15-PGDH expression or both reduced COX-2 expression, and finally reduced PGE2 levels in MCF-7/ADR cells. Effect of chemosensitivity and apoptosis induction of ADM was enhanced and multidrug resistance was partially reversed when co-treated with 15-PGDH induction drugs. CONCLUSION: The expression of 15-PGDH is decreased in human multidrug-resistant breast cancer line MCF-7/ADR. 15-PGDH induction drugs could increase chemosensitivity, promote apoptosis and reverse resistance of MCF-7/ADR cell, the mechanism might related to the influence of PGE2 level by regulated the expression of 15-PGDH and COX-2.

Preparation and Application of Ornidazole Magnetic Imprinted Polymers with Dual Functional Monomers / 分析化学

The magnetic molecularly imprinted polymers ( MMIPs ) was synthesiZed by suspension polymers technique using ornidaZole ( ONZ) as template, and methacrylic acid ( MAA) and acrylamide ( AA) as the binary functional monomers.The MMIPs were characteriZed by means of scanning electron microscopy ( SEM ) , Fourier transform infrared spectroscopy ( FT-IR ) , vibrating sample magnetometer ( VSM ) , thermogravimetric analysis ( TGA) and ultraviolet-visible ( UV-Vis) spectrophotometer.The results indicated that the adsorption capacity of MMIPs using the binary functional monomers to ONZ was higher than that using single functional monomer or that of its structural analogues.The Scatchard plot revealed that the template polymer system had a two-site binding behavior and the MMIPs exhibited the maximum rebinding to ONZ at 48.96 μmol/g and 10.60 μmol/g.Combined with high performance liquid chromatographic analysis technology, the prepared MMIPs were successfully applied to extract and enrich trace nitroimidaZoles from river water samples with recoveries range of 85.4%-104.3%.The precision of the results was good, and the manipulation of the developed method was simple and fast comparing to other methods.