Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs / 国际口腔科学杂志·英文版

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.

Identification of Weak D Type 1 in Rh Blood Group System and Discussion of Transfusion Strategy / 中国实验血液学杂志

OBJECTIVE@#To investigate the molecular mechanism of one patient with abnormal serological phenotype in RhD and discuss the transfusion strategy.@*METHODS@#The RhD variant sample was screened from a patient with IgM type anti-D antibody and further determined by three different sources of anti-D antibodies. Ten exons and the adjacent introns of the RHD gene were amplified, purified and sequenced. RhCE phenotypes and RHCE genotypes were detected.@*RESULTS@#The patient with Rh variant showed abnormal results of serological tests. The RHD gene sequence analysis showed that the RHD*01W.01 with a variation (c.809T>G, p.Val270Gly) in exon 6 of the RHD gene was found in the patient. The RhCE phenotype was CcEe. The genotyping results of RHCE were consistent with the serological typing results.@*CONCLUSION@#The Rh variant of the patient is RHD*01W.01, these findings indicate that RhD variants should be analyzed by molecular assays for the sake of safe transfusion.

Meta analysis on acceptance rate of HIV pre-exposure prophylaxis among men who have sex with men in China / 中华预防医学杂志

Objective: To systematically evaluate the acceptance of pre-exposure prophylaxis (PrEP)among men who have sex with men (MSM) in China, so as to provide reference for the promotion of preventive drug use before human immunodeficiency virus exposure in China. Methods: By searching the databases of China national knowledge infrastructure, VIP database, Wanfan knowledge service platform, PubMed, Web of Science, Embase and The Cochrane Library with key words of "men who have sex with men" "pre-exposure prophylaxis" "PrEP" and "MSM". The literature on the willingness of Chinese MSM population to accept PrEP was systematically collected, and the data of the literature meeting the inclusion criteria were extracted for Meta analysis. Results: A total of 12 articles were selected in this study, including 6 articles in English and 6 in Chinese. The score of bias risk assessment of eligible articles was 14-18, which was more than 70% of the total score. The total number of samples was 11 269. The overall acceptance rate of PrEP was 0.77(95%CI:0.71-0.82). In subgroup analysis, the acceptance rates of different nationalities, marriage, household registration, age, education background, income, sexual orientation, sexual behavior and awareness of PrEP were statistically significant. Conclusion: In general, the acceptance rate of PrEP in MSM population is higher, but the awareness rate is low. There are differences in the acceptance rate among different groups.

Flap combined with 3D printed microporous tianium(tantalum)prosthesis in the treatment of lower extremity soft tissue defect with large bone defect / 中华显微外科杂志

Objective:To investigate the effect of flap combined with 3D printed microporous titanium(tantalum)prosthesis in the treatment of lower extremity soft tissue defect with large bone defect.Methods:From January 2019 to December 2020, 2 patients with large soft tissue defects on dorsal foot together with large metatarsal bone defect and 4 patients with soft tissue defects of calf with large tibial bone defect were treated. The areas of soft tissue defect were 5.0 cm×8.0 cm-15.0 cm×10.0 cm. The length of the bone defect were 3.8 cm to 7.0 cm, 5.75 cm in average. In the first stage, metatarsal bone defect or tibial bone defect was filled with vancomycin blended bone cement, meanwhile, soft tissue defect was repaired with anterolateral femoral flap(ALTF) with vascular anastomosis in 2 cases of feet, and local fascia flap was trans-positioned in 4 cases of lower extremity defects. The sizes of repairing flap were 6.0 cm×8.5 cm-16.0 cm×11.0 cm. Two to 7 months after the initial surgery, the customer designed microporous titanium prostheses were used(5 cases with microporous titanium and 1 with microporous tantalum) to repair the bone defects. The wound healing, the integration of metatarsal and tibial fractures with 3D printed microporous titanium(tantalum) prostheses, and the walking condition were observed after surgery. The follow-up lasted from 6 to 25 months, with an average of 12.7 months.Results:The wound healing in 5 patients was good. The patients stood on the foot in 2 months after surgery, started to walk with the assistance of crutch in 3 months after surgery, and took walk without assistance in 5-6 months after surgery. Good osseous integration were achieved. One diabetic patient had infection of foot wound 3 months after surgery. After removal of microporous titanium prosthesis and replacement of vancomycin blended interstitial substance of bone cement, the wound healed and the patient resumed walking.Conclusion:It is an effective method to encourage the patients to take early ambulation after the surgery for lower extremity soft tissue defect with large bone defect that was repaired by a flap and 3D printed microporous titanium(tantalum)prosthesis. Further observations are required to investigate the long-term efficacy, and the reduction of prosthesis infection rate requires further exploration.

MicroRNA-130a Increases and Predicts Cardiotoxicity during Adjuvant Chemotherapy in Human Epidermal Growth Factor Receptor-2-Positive Breast Cancer / 한국유방암학회지

Purpose@#This study aimed to investigate the changes in microRNA-130a (miR-130a) and its correlation with cardiotoxicity during epirubicin/cyclophosphamide followed by docetaxel plus trastuzumab (EC-D+T) adjuvant chemotherapy in human epidermal growth factor receptor-2-positive (HER2+) breast cancer patients. @*Methods@#A total of 72 HER2+ breast cancer patients who underwent resection and were scheduled to receive EC-D+T adjuvant therapy were consecutively enrolled. The expression of miR-130a and cardiotoxicity (defined as any of the following situations: 1) absolute decline of left ventricular ejection fraction (LVEF) ≥ 10% and LVEF < 53%; 2) heart failure; 3) acute coronary artery syndromes; and 4) fatal arrhythmia) were assessed every 3 months throughout the 15-month EC-D+T treatment. @*Results@#The accumulating cardiotoxicity rate was 12 (16.7%), of which the incidence of heart failure, acute coronary syndrome, life-threatening arrhythmias, ΔLVEF ≥ 10%, and LVEF < 53% was 0 (0.0%), 1 (1.4%), 0 (0.0%), and 12 (16.7%), respectively. Baseline miR-130a expression was negatively correlated with LVEF (%) and positively correlated with cardiac troponin I. The expression of miR-130a gradually increased in both cardiotoxicity and noncardiotoxicity patients during EC-D+T treatment, while the increment of miR-130a was more obvious in cardiotoxicity patients compared with non-cardiotoxicity patients. Further logistic regression and receiver operating characteristic curve analysis indicated that miR-130a was an independent predictive factor for increased cardiotoxicity risk. @*Conclusion@#MiR-130a increases constantly and predicts high cardiotoxicity risk during ECD+T adjuvant chemotherapy in HER2+ breast cancer patients.

MicroRNA-130a Increases and Predicts Cardiotoxicity during Adjuvant Chemotherapy in Human Epidermal Growth Factor Receptor-2-Positive Breast Cancer / 한국유방암학회지

Purpose@#This study aimed to investigate the changes in microRNA-130a (miR-130a) and its correlation with cardiotoxicity during epirubicin/cyclophosphamide followed by docetaxel plus trastuzumab (EC-D+T) adjuvant chemotherapy in human epidermal growth factor receptor-2-positive (HER2+) breast cancer patients. @*Methods@#A total of 72 HER2+ breast cancer patients who underwent resection and were scheduled to receive EC-D+T adjuvant therapy were consecutively enrolled. The expression of miR-130a and cardiotoxicity (defined as any of the following situations: 1) absolute decline of left ventricular ejection fraction (LVEF) ≥ 10% and LVEF < 53%; 2) heart failure; 3) acute coronary artery syndromes; and 4) fatal arrhythmia) were assessed every 3 months throughout the 15-month EC-D+T treatment. @*Results@#The accumulating cardiotoxicity rate was 12 (16.7%), of which the incidence of heart failure, acute coronary syndrome, life-threatening arrhythmias, ΔLVEF ≥ 10%, and LVEF < 53% was 0 (0.0%), 1 (1.4%), 0 (0.0%), and 12 (16.7%), respectively. Baseline miR-130a expression was negatively correlated with LVEF (%) and positively correlated with cardiac troponin I. The expression of miR-130a gradually increased in both cardiotoxicity and noncardiotoxicity patients during EC-D+T treatment, while the increment of miR-130a was more obvious in cardiotoxicity patients compared with non-cardiotoxicity patients. Further logistic regression and receiver operating characteristic curve analysis indicated that miR-130a was an independent predictive factor for increased cardiotoxicity risk. @*Conclusion@#MiR-130a increases constantly and predicts high cardiotoxicity risk during ECD+T adjuvant chemotherapy in HER2+ breast cancer patients.

Identification and analysis of a case with Bw11 subtype / 中华医学遗传学杂志

OBJECTIVE@#To analyze serological and molecular characteristics of a case with Bw11 subtype.@*METHODS@#The ABO antigen and antibody in serum were respectively detected with the classical tube method, microcolumn gel method, and absorption and diffusion method. The ABO genotype was determined with PCR using sequence-specific primers (PCR-SSP). Exons 1-7 of the ABO gene were analyzed by Sanger sequencing. Haplotype analysis was carried out for exons harboring variants.@*RESULTS@#Forward and reverse typing with the microcolumn gel method has suggested type O, while forward and reverse typing with the classical tube method yielded inconsistent results. Absorption and diffusion test confirmed presence of B antigen. Antibody screening excluded presence of alloantibodies. The result of PCR-SSP suggested a B/O1 genotype.A 695T>C variant was identified in exon 7 as compared with the B101/O01 allele, which resulted in conversion of Leucine to Proline at position 232, and was confirmed as Bw11/O1 heterozygote.@*CONCLUSION@#The nt695T>C variant probably underlay the weakening of B antigenin the individual. There may be strong anti-B antibodies in Bw11 subtypes. Human-derived and certain monoclonal reagents may not detect Bw11 subtypes which is easy to be misjudged as type O. Application of molecular methods can identify ABO subtypes with accuracy.

Identification of an IDO1 inhibitor prodrug that specifically targets tumor tissue / 药学学报

Hypoxia-activated prodrugs that specifically target tumor tissues were designed by attaching the nitro-aromatic ring carrier molecules that can be degraded in the hypoxic microenvironment of the tumor to the hydroxyamidine group of IDO1 inhibitor compound B and epacadostat. Eleven prodrug compounds were synthesized and their structures were confirmed by 1H NMR and HR-MS. Compounds F-1 and F-6, which had a higher stability and drug release rate, were identified by an in vitro stability assay, nitroreductase reduction assay, MTT assay, and an in vivo tumor tissue hypoxia degradation assay, and then evaluated for anti-tumor efficacy in vivo. The results showed that prodrug F-1 inhibited tumor growth by 67.41%, which was significantly higher than 42.31% for the starting drug group. It appeared that the inhibition of IDO1 in the tumor tissue was different from the overall inhibition of IDO1 in vivo. Animal treatment procedures were carried out with the approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College.

Correlation of Mycoplasma genitalium infection with semen parameters and sperm DNA integrity in male infertility patients / 中华男科学杂志

Objective@#To analyze the relationship of Mycoplasma genitalium (MG) infection with routine semen parameters and sperm DNA integrity in male infertility patients.@*METHODS@#Totally, 114 semen samples, 34 MG-positive and 80 MG-negative, were collected from male infertility patients and subjected to routine semen analysis with the computer-assisted sperm analysis system, Papanicolaou staining for observation of sperm morphology, and sperm chromatin diffusion (SCD) test for detection of sperm DNA integrity. Semen parameters and DNA integrity were compared between the MG-positive and MG-negative groups with SPSS 21.0 statistical software and the relationship between the semen parameters and DNA integrity analyzed by Pearson correlation analysis.@*RESULTS@#The MG-positive samples, compared with the MG-negative ones, showed significantly decreased semen volume (［2.87 ± 0.37］ vs ［3.86 ± 0.43］ ml, P 0.05).@*CONCLUSIONS@#MG infection may be an important factor affecting sperm quality in male infertility patients. Active prevention and treatment of MG infection can help prevent male infertility.

Colonoscopy Adherence and Related Factors Among Preliminary Screened-Positive Population in Guangzhou：A Follow-Up Study / 中山大学学报(医学科学版)

@#【Objective】To explore colonoscopy adherence and related factors among preliminary screened-positive population in Guangzhou. 【Methods】This study was a part of the Guangzhou Community-based Colorectal Cancer Screening Program. We retrospectively analyzed the 1-year follow-up data of population aged 50~74 years old and positive in preliminary colorectal cancer screening in 2015. Kaplan- Meier method was used to describe the respond time to colonoscopy examination. Cox proportional hazard model was performed to identify factors associated with colonoscopy adherence. The effect of studied factors on colonoscopy adherence was reported according to hazard ratio（HR）.【Results】 A total of 18 604 preliminary screened-positive residents were included ，among whom 4 014 completed colonoscopy examination within one year，with a colonoscopy adherence of 21.6% . Colorectal lesions were found in 2 012 cases （50.1%），of which 96（2.4%）were colorectal cancers. The adherence of 1 month，3 months and 6 months were 9.7% ，15.8% ，and 18.6% respectively. Multivariate Cox regression analysis showed that those who were female ，in older age ， unmarried/widowed/divorced，without health insurance，and had a history of chronic cholecystitis or cholecystectomy were less likely to undergo colonoscopy；while those who were fecal occult blood test- positive，had colonoscopy preferential policies，worked in government or public institution，had medical insurance for urban workers，had a history of chronic diarrhea，a history of chronic constipation，a history of mucous and/or blood stool，and a history of bad life incidents were more likely to undergo colonoscopy. 【Conclusions】 This study suggested that the colonoscopy adherence of preliminary screened- positive population in Guangzhou was low and such low adherence was associated with different factors. Community health workers should timely track the completion of colonoscopy of preliminary screened-positive residents ， and take targeted measures to promote colonoscopy adherence.

Effect and Mechanism of Celastrol on Endoplasmic Reticulum Stress in Hepatic L02 Cells of Nonalcoholic Fatty Liver Disease / 中国实验方剂学杂志

Objective:To explore the effect of celastrol in inhibiting the lipid metabolism disorder in hepatic L02 cells and its possible mechanism on endoplasmic reticulum stress (ERS) of non-alcoholic fatty liver cells by intervening non-alcoholic fatty liver disease(NAFLD) cell model with celastrol. Method:Hepatic L02 cells were divided into control group, model group, low-dose celastrol treatment group (Cel 0.5 mg·L-1), high-dose celastrol treatment group (Cel 1 mg·L-1) and simvastatin group (SIM 6 mg·L-1) for cultivation. The contents of total cholesterol (TC) and total triglyceride (TG) in hepatic L02 cells were detected, and the oil red staining was used to detected the lipid accumulation in hepatic L02 cells. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the mRNA and protein expression levels of endoplasmic reticulum stress (ERS)-related signal molecules activating transcription factor 6 (ATF6), glucose regulated protein 78 (GRP78), inositol-requiring enzyme 1 (IRE1), sterol regulatory element-binding protein cleavage-activating protein (SCAP), sterol regulatory element-binding protein-1c (SREBP-1c) and sterol regulatory element-binding protein-2 (SREBP-2) in hepatic L02 cell model respectively. Result:The contents of TC and TG in hepatic L02 cells of NAFLD group were significantly higher than those in control group (P-1 group, Cel 1 mg·L-1 group and SIM 6 mg·L-1 group were significantly lower than those in NAFLD group (P-1 group, the Cel 1 mg·L-1 group, and the SIM 6 mg·L-1 group were lower than the NAFLD group to different degrees. According to the results of RT-PCR and Western blot, the mRNA transcription and protein expression levels of ERS-related signaling molecules ATF6, GRP78, IRE1, SCAP, SREBP-1c and SREBP-2 in hepatic L02 cells of NAFLD group were higher than those of control group (P-1 group, Cel 1 mg·L-1 group and SIM 6 mg·L-1 group were lower than those of NAFLD group (P-1 group and the SIM 6 mg·L-1 group. Conclusion:Celastrol can reduce the lipid metabolism disorder in hepatic L02 cells by down-regulating the expressions of ERS-related signaling molecules ATF6, GRP78, IRE1, SCAP, SREBP-1c and SREBP-2 in hepatic L02 cells, so as to improve NAFLD.

Clinical analysis of laparoscopic remedial surgery for endoscopic lesions in early colorectal cancer / 中华肿瘤杂志

Objective@#To investigate the safety and feasibility of laparoscopic remedial surgery in patients who didn′t reach the cure criterion of early colorectal cancer after endoscopic resection.@*Methods@#The clinical and follow-up data of 12 patients who didn′t reach the cure criterion of early colorectal cancer and then underwent endoscopic resection was collected. The clinicalpathological features and remedial indications were analyzed to evaluate the effects of laparoscopic remedial surgery.@*Results@#The average number of lymph nodes in the lymph node dissection was 15 during remedial surgery, and 3 of them had lymph node metastasis. Among the 3 patients with residual cancer, two cases were poorly differentiated, 1 case was moderately differentiated, 1 case was positive for basal margin, and 1 case had vascular invasion. No lymph node metastasis occurred in the 9 patients who had no residual cancer. Among these, 8 cases were moderately differentiated, 1 case was poorly differentiated and 2 cases had positive basal margin. The average follow-up duration was 40 months and all 12 patients were in a state of survival at the last follow-up. During the follow-up of the 3 patients with residual cancer, 1 patient received adjuvant chemotherapy with unknown prognosis; 1 patient received postoperative adjuvant radiochemotherapy, and lung metastasis occurred; 1 patient did not receive any treatment after surgery and survived for 33 months.@*Conclusions@#Laparoscopic remedial surgery is a safe and feasible remedy for patients who didn′t reach the cure criterion of early colorectal cancer after endoscopic resection. However, the choice of remedial strategy for colorectal carcinoma needs further investigation for patients with no vascular invasion, high degree of differentiation, and negative basal margin.

Predictive value of protein C for long-term mortality of patients with community-acquired pneumonia / 中国基层医药

Objective@#To investigate the predictive value of protein C(PC) for long-term mortality of patients with community-acquired pneumonia(CAP).@*Methods@#A total of 657 patients with CAP were enrolled in Taian Central Hospital from January 2011 to December 2011.The patients were divided into short-term group(≤30 days), medium-term group(>30~90 days) and long-term group(>90 days). PC, high sensitivity C-reactive protein(hs-CRP), procalcitonin(PCT), pneumonia severity index(PSI) score and CURB-65 score were measured at the time of admission.The ROC curve was used to evaluate the independent risk factors.The Kaplan-Meier survival function curve was used to analyze the difference of mortality between the short-term group and long-term group.Independent risk factors for CAP risk were analyzed by COX regression.@*Results@#A total of 597 cases were followed up, there were 49 cases(8.09%) in the short-term group, 11 cases(1.84%) in the medium-term group, and 537 cases(89.93%) in the long-term group.The PC levels in the short-term group, medium-term group and long-term group were (32.2±10.6)%, (43.1±9.9)%, (69.6±23.0)%, respectively.The level of PC was significantly increased in the short-term group compared with the medium-term group and long-term group (short-term group vs.medium-term group, q=6.18, P<0.05, short-term group vs.long-term group, q=9.87, P<0.05). The hs-CRP levels in the short-term group, medium-term group and long-term group were (108.1±22.4)mg/L, (68.2±12.9)mg/L, (25.1±17.1)mg/L, respectively.The level of hs-CRP was significantly increased in the short-term group compared with the medium-term group and long-term group (short-term group vs.medium-term group, q=5.23, P<0.05, short-term group vs.long-term group, q=12.95, P<0.05). Meanwhile, PC showed higher accuracy(AUC, 0.889) than CURB-65(AUC, 0.828) and hs-CRP(AUC, 0.711) in the long-term group.The Kaplan-Meier survival function curve showed that the mortality rate was significantly higher in the high-value group compared with the low-value group(F=17.10, P<0.01). PC was an independent factor for long-term mortality and was associated with poorer survival by the COX regression analysis.@*Conclusion@#PC has a high predictive value for long-term mortality in CAP patients.

Predictive value of protein C for long-term mortality of patients with community-acquired pneumonia / 中国基层医药

Objective To investigate the predictive value of protein C( PC) for long -term mortality of patients with community-acquired pneumonia(CAP).Methods A total of 657 patients with CAP were enrolled in Taian Central Hospital from January 2011 to December 2011.The patients were divided into short-term group(≤30 days),medium-term group(>30~90 days) and long-term group(>90 days).PC,high sensitivity C-reactive protein(hs-CRP),procalcitonin(PCT),pneumonia severity index(PSI) score and CURB-65 score were measured at the time of admission.The ROC curve was used to evaluate the independent risk factors.The Kaplan-Meier surviv-al function curve was used to analyze the difference of mortality between the short-term group and long-term group. Independent risk factors for CAP risk were analyzed by COX regression.Results A total of 597 cases were followed up,there were 49 cases(8.09% ) in the short-term group,11 cases(1.84% ) in the medium -term group,and 537 cases(89.93% ) in the long-term group.The PC levels in the short-term group,medium-term group and long-term group were (32.2 ± 10.6)% ,(43.1 ± 9.9)% ,(69.6 ± 23.0)% ,respectively.The level of PC was signifi-cantly increased in the short-term group compared with the medium-term group and long-term group ( short-term group vs.medium-term group,q =6.18,P <0.05,short -term group vs.long -term group,q=9.87,P <0.05).The hs-CRP levels in the short-term group,medium-term group and long-term group were (108.1 ± 22.4)mg/L,(68.2 ± 12.9 ) mg/L, ( 25.1 ± 17.1 ) mg/L, respectively. The level of hs - CRP was significantly increased in the short-term group compared with the medium-term group and long-term group (short-term group vs.medium-term group, q =5.23, P <0.05, short -term group vs. long -term group, q =12.95, P<0.05 ). Meanwhile,PC showed higher accuracy(AUC,0.889) than CURB-65( AUC,0.828) and hs-CRP( AUC,0.711) in the long-term group.The Kaplan-Meier survival function curve showed that the mortality rate was significantly higher in the high-value group compared with the low-value group(F=17.10,P<0.01).PC was an independent factor for long - term mortality and was associated with poorer survival by the COX regression analysis. Conclusion PC has a high predictive value for long-term mortality in CAP patients.

Progress of anti-tumor mechanisms of reovirus / 肿瘤研究与临床

Oncolytic viruses have made great breakthroughs in cancer treatment, especially for reovirus, which can effectively induce the death of tumor cells without harming the normal tissues. More than 80％ tumor cells are sensitive to reovirus infection. Reovirus induces the apoptosis of tumor cells and exerts anti-tumor immunity to achieve anti-tumor activity, and the curative effect of combination therapy with reovirus and chemotherapeutic drugs exceeds the effect of monotherapy. Reovirus can exert anti-tumor effects through different mechanisms, which is of great significance for the new and effective treatment of tumors in the future.

Effects of individualized testosterone replacement therapy on serum total testosterone and sex hormone levels in male patients with late-onset hypogonadism / 实用医学杂志

Objective To observe the effects of individualized testosterone replacement therapy on serum total testosterone(TT)and sex hormone in males with late-onset hypogonadism(LOH). Methods A total of 78 cases with LOH males were divided into group A(TT<8 nmol/L)and group B(8≤TT<11.5 nmol/L)according to the serum TT level,and the B group was randomly divided into the B1 group and the B2 group.They were given the individualized testosterone replacement therapy,and the treatment effect was compared among the 3 groups. Results After treatment,the SHBG level in the 3 groups was significantly reduced(P<0.05)whereas the serum TT level was significantly higher(P<0.05). The TT level in the B1 group was significantly higher than that in the B2 group(P ＜0.05). The levels of E2and FSH in the 3 groups were significantly lower(P ＜0.05)whereas the level of P was significantly higher(P ＜0.05). The ADAM scores in the 3 groups were significantly better than those before treatment(P<0.05),and there was no significant difference between the B1 group and the B2 group (P ＞0.05). There was no significant difference in the total incidence rate of adverse reactions between the group A and the other two groups(P ＞0.05),and the rate in the B2 group was lower than that in the B1 group(P <0.05). Conclusions In supplementary treatment of LOH,TT ＜8 nmol/L recommended to choose conventional dose,and 8≤TT<11.5 nmol/L can choose a small dose of testosterone.

Correlations between the levels of serum Wnt5a, Sfrp5, and glycemic control in elderly male patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective To investigate the levels of serum Wnt5a and Sfrp5 in elderly male patients with type 2 diabetes mellitus (T2DM), and identify associations between their levels and glycemic control. Methods A total of 67 elderly male T2DM patients and 65 nondiabetic subjects were studied. Participants were divided into four groups:normal control (NC group), T2DM patients were categorized by HbA1C quartile(Group Ⅰ: HbA1C<7％, Group Ⅱ:7％≤HbA1C < 9％, Group Ⅲ: HbA1C ≥9％). The serum Wnt5a and Sfrp5 concentrations were measured through ELISA. Influencing factors for Wnt5a and Sfrp5 were analyzed. Results Compared with the NC group, Wnt5a levels of elderly T2DM were decreased in groups Ⅱ and Ⅲ, in contrast, Sfrp5 levels were elevated in groups Ⅱ and Ⅲ than NC group(all P<0.05). Spearman correlation analysis suggested that Wnt5a levels were negatively correlated with HbA1C , GA, FPG, and 2hPG(r were -0.277, -0.298, -0.185, and -0.254 respectively, all P<0.05);Sfrp5 levels were positively correlated with HbA1C , GA, and FPG(r were 0.311, 0.247, and 0.200 respectively, all P<0.05) while negatively correlated with BMI and LDL-C( r were - 0.193 and - 0.190, both P< 0.05). Multivariate linear regression analysis showed that HbA1C was an independent association factor for Wnt5a, and FPG was an independent association factor for Sfrp5. Conclusions In the elderly male T2DM with worse glycemic control, Wnt5a levels were more decreased, and in contrast, Sfrp5 levels were elevated. This result indicated that Wnt5a and Sfrp5 may be associated with the level of glycemic control in elderly male T2DM patients.

The anti-tumor activity and mechanisms of a GLI1 inhibitor FL18 in suppression of glioblastoma growth / 药学学报

The abnormal activation of hedgehog (HH) signaling pathway plays an important role in the development and progression of glioblastoma (GBM). As a transcription factor at the end of the HH pathway, the final effector of glioma-associated oncogene homoglog-1 (GLI1) is an important target in the treatment of GBM. The study was designed to evaluate the anti-tumor activities and mechanisms of a novel GLI1 inhibitor FL18 in GBM. MTT and colony formation assay were performed to determine anti-proliferation activity of FL18 in vitro. The effect of FL18 on cell apoptosis was measured by flow cytometry (FCM) analysis. Transwell experiment was used to explore the inhibitory activity of FL18 in cell invasion. In vivo experiments, the subcutaneously transplanted and orthotopic U-87 MG GBM xenograft model were used to study the activity of FL18 on tumor growth. The optimized dual report gene screening model was used to detect the effect of FL18 on the transcriptional activity of GLI1. Western blot assay was used to study the mechanisms of action of FL18. The results showed that the IC50 of FL18 in glioblastoma was in the nanomole level in vitro. It was observed that 22.5 and 45 mg·kg-1 FL18 reduced the tumor volume with the rate of 55.4% and 89.8% in xenograft model in mice in situ. The IC50 of FL18 on the inhibition of GLI1 transcriptional activity was 3.32×10-11 mol·L-1 analyzed by the optimized dual report gene screening model. By the Western blot experiments, it was proved that FL18 inhibited expression of GLI1 without influencing the upstream canonical HH/SMO signaling and cross-talk oncogenic pathway, such as ERK and AKT signaling. The results also demonstrated that FL18 significantly downregulated GLI1 target genes such as Bcl-2, MMP2 and MMP9 and increased the expression of c-caspase3, c-PARP and Bax. These data suggest that FL18 may generate the anti-glioma activity by inhibition of GLI1.

Identification of a Rare Ael05/B101 Subtype and Selection of Blood Transfusion Strategy / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the mechanism of ABO discrepancy in a patient by ABO genotyping and the reasonable blood transfusion strategy.</p><p><b>METHODS</b>Routine serological test was carried out to analyze ABO blood group. The presence of the blood group determinants on the red blood cells were determined by adsorption-elution test. Exons 1-7 and adjacent introns of the ABO gene were amplified by PCR and sequenced.</p><p><b>RESULTS</b>The patient showed ABO forward and reverse typing discrepancy. ABO forward typing defined as B, however, the reverse typing indicated that the patient was AB subtype. Absorption-elution test confirmed weak A antigens on the patient's red blood cells. The ABO gene sequencing showed a T>C exchange at position in exon 7 which resulted in a isoleucine to threonine substitution at codon 256. The ABO blood group genotype was ABO*Ael05/B101.</p><p><b>CONCLUSION</b>The 767 T>C substitution in the gene of α-1,3-N-acetyl galactose is the molecular mechanism leading to the decrease expression of A antigen of the Ael05 subtype.</p>

Angiotensin-(1-7) protects cardiac myocytes against high glucose-induced injury by inhibiting ClC-3 chloride channels / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore whether angiotensin-(1-7) [Ang-(1-7)] protects cardiac myocytes against high glucose (HG)-induced injury by inhibiting ClC-3 chloride channels.</p><p><b>METHOD</b>H9c2 cardiac cells were exposed to 35 mmol/L glucose for 24 h to establish a cell injury model. The cells were treated with Ang-(1-7) or the inhibitor of chloride channel (NPPB) in the presence of HG for 24 h to observe the changes in HG-induced cell injury. Cell counter kit 8 (CCK-8) assay was used to test the cell viability, and the morphological changes of the apoptotic cells were detected using Hoechst 33258 staining and fluorescent microscopy. The intracellular level of reactive oxygen species (ROS) was examined by DCFH-DA staining, SOD activity in the culture medium was measured using commercial kits, and the mitochondrial membrane potential (MMP) of the cells was tested with rodamine 123 staining. The expression level of cardiac ClC-3 chloride channels was detected with Western blotting.</p><p><b>RESULTS</b>Exposure of H9c2 cardiac cells to 35 mmol/L glucose for 24 h markedly enhanced the expressions of cardiac ClC-3 channel protein (P<0.01). Co-treatment of the cells with 1 µmol/L Ang-(1-7) and HG for 24 h significantly attenuated HG- induced upregulation of ClC-3 channel protein expression (P<0.01). Co-treatment of the cells exposed to HG with 1 µmol/L Ang-(1-7) or 100 µmol/L NPPB for 24 h obviously ameliorated HG-induced injuries as shown by increased cell viability, enhanced SOD activity, decreased number of apoptotic cells, and reduced intracellular ROS generation and loss of MMP (P<0.01).</p><p><b>CONCLUSION</b>ClC-3 channels are involved in HG-induced injury in cardiac cells. Ang-(1-7) protects cardiac cells against HG-induced injury by inhibiting ClC-3 channels.</p>