Objective:To clarify the causal relationship between obesity and male infertility through Mendelian randomization(MR)study.Methods:We assessed the causal effect of genetically predicted body mass index(BMI)on the risk of male infertility via a two-sample MR analysis,with the BMIs of 99 998 cases and 12 746 controls as the exposure factor and genetic information on male infertility obtained from a genome-wide association study of 73 479 Europeans.In the univariable MR(UVMR)analysis of the causal relationship,we mainly used inverse variance weighting(IVW),with MR-Egger regression and weighted median filtering as the supplementary methods.Sensitivity analyses including the Cochran's Q test,Egger intercept test,MR-PRESSO,leave-one-out analysis and funnel plot were performed to verify the robustness of the MR results.To evaluate the direct causal effects of BMI on MI risk,mult-ivariable MR(MVMR)was performed.Results:UVMR indicated a causal relationship between genetically predicted BMI and an in-creased risk of male infertility(OR:1.237,95%CI:1.090-1.404,P=0.001).Sensitivity analysis revealed little evidence of bias in the current study(P>0.05).With such risk factors as type 2 diabetes,alcohol consumption and smoking adjusted,MVMR confirmed a direct causal effect of genetically predicted BMI on the risk of male infertility(P<0.05).Conclusion:Genetically pre-dicted BMI may be associated with an increased risk of male infertility.Further studies are expected to explore the underlying mecha-nisms of this association and provide some new strategies for the prevention and treatment of BMI-related male infertility.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Transcatheter arterial chemoembolization (TACE) is the most commonly used method for non-surgical treatment of liver cancer, and it is usually used as an adjuvant therapy in patients who have not developed intrahepatic metastases after surgical resection. Postoperative adjuvant TACE therapy may provide a prognostic benefit in liver cancer patients with high recurrence risk. This article reviews the research progress of adjuvant TACE therapy for liver cancer after radical resection.
Carcinoma, Hepatocellular/pathology* ; Chemoembolization, Therapeutic/methods* ; Hepatectomy ; Humans ; Liver Neoplasms/pathology* ; Neoplasm Recurrence, Local/pathology* ; Retrospective Studies

OBJECTIVE: To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (, QHP) or low-intensity chemotherapy (LIC). METHODS: Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed. RESULTS: Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients' preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, >0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all >0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age> 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (>0.05). CONCLUSION QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.
Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Arsenicals ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; Male ; Middle Aged ; Powders ; Retrospective Studies

BACKGROUND: We previously found that the intestinal epithelial chemokine (C-C motif) ligand 7 (CCL7) plays an important role in the development of toxin-induced acute liver damage. The detailed effects of intestinal epithelial CCL7 on chronic diseases; however, are still unclear. Here, we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet (HFD)-induced obesity and steatohepatitis in mice. METHODS: Intestinal epithelial CCL7 overexpression (CCL7) mice and their wild-type (WT) littermates were fed with normal chow or HFD for 16 weeks to induce obesity and non-alcoholic fatty liver disease. Body weight gain, as well as adipose tissue index were assessed. Liver injury was monitored by histological analysis and real time polymerase chain reaction. Gut microbial composition was analyzed by 16S rRNA gene sequencing. RESULTS: We found that the CCL7 mice on a HFD had markedly decreased weight gain (8.9 vs. 17.0 g, P < 0.05) and a lower adipose tissue index that include mesenteric fat (1.0% vs. 1.76%, P < 0.05), gonadal fat (2.1% vs. 6.1%, P < 0.05), subcutaneous fat (1.0% vs. 2.8%, P < 0.05) compared to WT animals. HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7 mice compared to WT. Furthermore, HFD-fed CCL7 mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice. 16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis. CONCLUSIONS Our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity, hepatic steatosis, and enteric dysbiosis.

Objective To evaluate the antibody titer distributions after primary vaccination by different sequential schedules of Sabin strain-based inactivated poliovirus vaccine(sIPV) and bivalent oral attenuated live poliomyelitis vaccine against types 1 and 3 (bOPV) in Drug Candy(DC) form or liquid dosage form. Methods Eligible infants of 2 months old selected in Liuzhou were assigned randomly in a ratio of 1:1:1:1 to 4 groups as following: sIPV+2bOPV(DC), sIPV+2bOPV(liquid), 2sIPV+bOPV(DC), 2sIPV+bOPV(liquid), and were vaccinated at 0, 28, 56 days. Polio neutralizing antibody titers against poliovirus types 1, 2 and 3 were tested prior to Dose 1 and at 28 days after Dose 3. Results The antibody titer distribution for type 1 was statistically different between sIPV+2bOPV(DC) and sIPV+2bOPV(liquid) (Z=-2.589, P=0.010) while no significant differences were detected between the two groups for type 2(Z=-0.331, P=0.741) and type 3(Z=-1.556, P=0.120). There were no significant differences between 2sIPV +bOPV(DC) and 2sIPV+bOPV(liquid) for the distributions(All P>0.05) (type 1: Z=-1.249, P=0.212; type 2: Z=-1.658, P=0.097; type 3: Z=-1.436, P=0.151). In the same dosage forms with different sequential schedules, the antibody titer distributions were significantly different between 2 doses sIPV and 1 dose sIPV groups(All P<0.05)(sIPV+2bOPV(liquid) vs 2sIPV+bOPV(liquid): type 1: Z=-2.766, P=0.006; type 2: Z=-9.137, P<0.001; type 3: Z=-5.529, P<0.001. sIPV+2bOPV(DC) vs 2sIPV+bOPV(DC): type 1: Z=-3.748, P<0.001; type 2: Z=-7.660, P<0.001; type 3: Z=-6.030, P<0.001). Conclusions Different dosage forms have similar immune effects, so appropriate dosage forms should be selected for vaccination according to the effectiveness, characteristics of subjects and the population density. In the case of sufficient supply of sIPV, 2 doses sIPV sequential program should be the first choice to complete the primary immunization.

【Objective】 To investigate the relationship between the expression of PRDX3 （thioredoxin-dependent peroxide reductase）and the occurrence and development of ccRCC （clear cell renal cell carcinoma）. 【Methods】 The expression of PRDX3 was first verified in 16 cases of ccRCC tissues and adjacent normal tissues. In the present study ， according to the PRDX3 over-expression level，we established the stable PRDX3 overexpression cell lines and knockdown cell lines in 786-O cell lines. We detected the growth rate of tumor cells after overexpression and knockdown of PRDX3. Interaction proteins with PRDX3 were searched by anti-flag pull-down test combined with LC- MS/MS technique. The interaction between PRDX3 and PRDX1（peroxiredoxin 1）was preliminarily explored.【Results】The western blot results showed that PRDX3 were down- regulated in 14 out of 16 ccRCC tissue samples about 1.78 times. Stable PRDX3 overexpression and knockdown cell lines and those control group were successfully established［786O- PRDX3（+）and 786O- PRDX3（-），786O- PRDX3 KN and 786O- PRDX3 NCi］. PRDX3 expression in 786O- PRDX3（+）was 2.1 times higher than 786O- PRDX3（-）at mRNA level and 1.8 times at protein level. PRDX3 expression in 786O- PRDX3 KN was 0.48 times lower than 786O-PRDX3 NCi at mRNA level and 0.51 times at protein level. The cell growth rate of 786O-PRDX3 （+）cell lines was significantly lower than that of 786O-PRDX3（-）. Meanwhile ，there was no significant difference in 786O-PRDX3 KN and NCi cell lines. Pull-down results shows that PRDX3 may interact with PRDX1 through disulfide bond and the binding sites of those two proteins were identified respectively.【Conclusion】PRDX3 was down- regulated expression in renal clear cell carcinoma and the interaction with PRDX1 may be involved in the occurrence and development of tumor. Increasing the expression level of PRDX3 can significantly reduce the growth rate of tumor cells. Based on PRDX3 ，it is possible to develop targeted drugs for treating renal clear cell carcinoma.

Objective: To investigate the effect of alpha-lipoic acid (α-LA) combined with tamoxifen citrate (TC) in the treatment of oligoasthenospermia. METHODS: From June to November 2016, we treated 60 patients with oligoasthenospermia in our Department of Andrology, 30 (the trial group) with oral α-LA (0.6 g, qd) + TC (20 mg, qd) and the other 30 (the control group) with oral L-carnitine (1g, bid) + TC (20 mg, qd). Before and after 3 months of medication, we examined the semen parameters of the patients and the levels of their seminal oxidative stress biomarkers, including methylenedioxyamphetamine (MDA) and total antioxidant capacity (TAC) in the seminal plasma. We also compared the pregnancy rate and adverse reactions between the two groups. RESULTS: Totally, 57 of the patients completed the treatment, 28 in the trial group and 29 in the control. Compared with the baseline, the patients of the trial group showed significant improvement after 3 months of medication in the semen volume (［2.50 ± 0.71］ vs ［3.37 ± 0.70］ ml, P <0.05), sperm concentration (［12.00 ± 1.65］ vs ［19.34 ± 2.04］ ×10⁶/ml, P <0.05), percentage of progressively motile sperm (PMS) (［18.01 ± 3.01］% vs ［35.41 ± 6.49］%, P<0.05), MDA level (［14.96 ± 2.76］ vs ［10.04 ± 1.04］ nmol/ml, P <0.05), and TAC in the seminal plasma (［9.83 ± 1.02］ vs ［12.25 ± 1.11］ U/ml, P <0.05), and so did the controls in the semen volume (［2.76 ± 0.67］ vs ［3.36 ± 0.93］ ml, P <0.05), sperm concentration (［11.47 ± 1.10］ vs ［17.77 ± 3.56］ ×10⁶/ml, P <0.05), percentage of PMS (［19.22 ± 1.41］ vs ［36.01 ± 5.22］ %, P <0.05), MDA level (［14.66 ± 2.75］ vs ［10.14 ± 1.01］ nmol/ml, P <0.05), and TAC in the seminal plasma (［9.84 ± 0.90］ vs ［11.14 ± 0.84］ U/ml, P <0.05). There were no statistically significant differences in the above post-medication parameters between the trial and control groups (P >0.05) except in TAC, which was markedly more improved in the former than in the latter (P <0.05), nor in the percentage of morphologically normal sperm before and after treatment in either of the two groups (P >0.05). After 3 months of treatment, 3 pregnancies were achieved in the trial group and 1 in the control (10.7% vs 3.45%, P >0.05). No obvious adverse events occurred during the treatment. CONCLUSIONS Alpha-lipoic acid combined with tamoxifen citrate can evidently improve semen parameters in oligoasthenospermia patients by relieving oxidative stress injury.
Antioxidants ; Asthenozoospermia ; drug therapy ; Biomarkers ; analysis ; Carnitine ; therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Male ; Oligospermia ; drug therapy ; Oxidative Stress ; Pregnancy ; Pregnancy Rate ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; drug effects ; Tamoxifen ; therapeutic use ; Thioctic Acid ; therapeutic use

OBJECTIVETo investigate the clinical characteristics and prognostic factors of patients with peripheral T cell lymphoma (PTCL).

METHODSThe clinical data of 46 elderly PTCL patients admitted in Tianjin Medical University Cancer Hospital from April 2008 to August 2014 were collected, the clinical features, prognostic factors and treatments, as well as followed-up outcome were analyzed retrospectively. Survival analysis was performed by Kaplan-Meier method, and the COX proportional hazard model was used to perform multivariate analysis.

RESULTSThe median survival time was 11 months, and the expected 1-year, 2-year and 3-year overall survival rate (OS) was 50%, 36% and 33%, respectively. Univariate analysis showed that the age, ECOG score, Charlson Comorbidity Index Score, the efficacy and course of chemotherapy were all the prognostic indicators affecting the OS and progression free survival (PFS) in this cohort of elderly patients. Multivariate analysis indicated that ECOG score and course of chemotherapy were the independent prognostic indicators affecting the OS and PFS (P < 0.05).

CONCLUSIONECOG score and course of chemotherapy are of great significance for predicting the prognosis in elderly PTCL patients. The elderly patients's general condition and completion of a certain intensity of chemotherapy are an important measure to prolong survival time in elderly PTCL patients.

Aged ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Lymphoma, T-Cell, Peripheral ; diagnosis ; pathology ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.
Antibodies, Monoclonal ; pharmacokinetics ; Cytotoxins ; pharmacokinetics ; Humans ; Immunoconjugates ; pharmacokinetics ; Neoplasms ; drug therapy