Androgen receptor (AR) plays a key regulatory role in the development of castration resistant prostate cancer (CRPC), and the level of constitutive active variants represented by androgen receptor variant 7 (AR-V7) is increasing during the progress of CRPC, which can be used as a molecular marker of disease progress and prognosis of patients with CRPC. It is an important target to overcome castration resistance and improve the quality of life and survival of patients. In this paper, the function of AR-V7 and its molecular regulation mechanism in CRPC are reviewed. The research shows that the generation of AR-V7 is related to the structural rearrangement of AR gene, gene amplification and the selective splicing of AR gene transcripts, and it is affected by the coordinated regulation of multiple signal pathway molecules such as TGF-β; AR-V7 changes the transport and nuclear localization mechanism of AR protein, and further affects the transcriptional expression of downstream target genes. AR-V7 antagonizes AR activity and blocks the differentiation process driven by AR and androgen, and inhibits the expression of tumor suppressor genes to stimulate the proliferation of tumor cells, thus promoting the progress of Pca. Related targeting studies have revealed AR-V7 targets and CRPC treatment strategies. Currently, they mainly focus on AR-V7 protein degradation, mRNA expression inhibition and N-terminal domain targeting intervention. With the development of in-depth research, the molecular mechanism of AR-V7 in the progress of Pca will be gradually clarified, which will certainly play a greater role in the prevention and treatment of CRPC.

Objective:To investigate the effect of calcium carbonate combined with vitamin K on bone metabolism indexes, Th1 cytokines and safety in children with glucocorticoid-induced osteoporosis.Methods:A total of 96 children with glucocorticoid-induced osteoporosis were enrolled in this study. They were randomly divided into control group and study group, 48 cases in each group. The control group was treated with calcium carbonate, and the study group was treated with calcium carbonate combined with vitamin K. The bone metabolism index serum total bone type Ⅰ collagen N-terminal peptide was compared between the two groups before and after treatment. PINP), serum β-Carboxy I terminal peptide ( β-CTX), osteocalcin (osteocalcin, P<0.05), and serum β-CTX. BGP), serum bone alkaline phosphatase (BALP), Th1 cytokine interferon- γ (IFN- γ), interleukin-2 (IL-2) levels and adverse reactions were also observed. Results:There was no statistical significance in the general data of the two groups (all P>0.05). Compared with that before treatment, bone mineral density of femoral neck increased in both groups after treatment, and the improvement in the study group (-1.02±0.49) was more significant than that in the control group (-1.52±0.65) ( t=4.26, P<0.001). Compared with those before treatment, the levels of PINP, β-CTX, BGP and BALP in 2 groups after treatment were decreased, and compared with those of the those of the control group (PINP: 31.65±6.58; β-CTX: 0.34±0.05; BGP: 4.95±1.28; BALP: 40.54±7.84), all indexes of the study group after treatment (PINP: 26.54±7.06; β-CTX: 0.24±0.03; BGP: 3.05±1.09; BALP: 35.96±7.02) improved significantly ( t=3.67, P<0.001; t=11.88, P<0.001; t=7.83, P<0.001; t=3.02, P<0.003). Compared with that before treatment, IL-2 level was increased while IFN- γ level was decreased in both treatment groups. Additionally, in comparison to the control group (IL-2: 163.89±30.85; IFN- γ: 196.61±21.05), IL-2 level (198.32±32.14) was higher and the IFN- γ level (163.25±18.43) was lower in the study group after treatment ( t=5.35, P<0.001; t=8.26, P<0.001). The incidence of adverse reactions between the two groups was not statistically significant ( χ2=0.15, P=0.695) . Conclusion:Calcium carbonate combined with vitamin K in the treatment of children with glucocorticoid-induced osteoporosis can improve bone metabolism indexes and Th1 cytokine levels in children, and the clinical therapeutic effect is good.

Ovarian tumor-associated protease B1(OTUB1) is a member of the deubiquitinase family. Its highly specific recognition and cleavage function of polyubiquitinated chains has attracted widespread attention, and it can regulate a variety of important signaling pathways, such as the epithelial-mesenchymal transition (EMT) pathway, the MAPK signaling pathway, and the p53-related signaling pathway. In recent years, it has gradually become a new direction of oncology research. More and more studies have proved that OTUB1 is closely related to various tumors such as hepatocellular carcinoma, colorectal cancer, and breast cancer. It regulates the occurrence, development, and prognosis of tumors. OTUB1 could be a potential treatment for tumors. Urinary tract tumors mainly include prostate cancer, bladder cancer, and renal cell carcinoma. In this review, the research progress on the correlation between OTUB1 and urological tumors was reviewed, including its important role in the occurrence and development of urological tumors and the possibility of treating urological tumors with OTUB1.

Objective:To observe the safety of intravitreal injection of triamcinolone acetonide (TA) combined with partial anterior pars plana vitrectomy (PPV) for cataract with severe vitreous hemorrhage.Methods:A retrospective case-control study. A total of 60 patients (60 eyes) with cataract and severe vitreous hemorrhage were included from June 2017 to June 2019 in Xi’an People’s Hospital (Xi’an Fourth Hospital). There were 32 males (32 eyes) and 28 females (28 eyes), with a mean age of 64.8 years. The eyes were randomly divided into intravitreal injection TA group (TA group) and non-TA injection group (control group), with 30 eyes in each group. Before phacoemulsification, 0.05-0.10 ml TA was injected into the vitreous cavity in the TA group and the vitreous besides the vitrectomy channel was removed. The eyes of the control group underwent conventional cataract phacoemulsification combined with PPV. The follow-up time after surgery was ≥6 months. The rate of success continuous circular capsulorhexis, posterior capsule rupture, and intraocular lens (IOL) implantation in the capsular bag were compared between the two groups. The statistical data were compared with χ2 test. Results:For all eyes in the TA group, after intravitreal injection of TA combined with partial anterior PPV, the white reflection of the fundus can clearly show the anterior and posterior capsule of the lens. Continuous circular capsulorhexis was completed, the posterior capsule was not broken, and the IOL was successfully implanted inside the capsular bag. Among the 30 eyes of the control group, 4 eyes did not complete continuous circular capsulorhexis. Radial tear occurred during capsulorhexis, and capsulorhexis was used to complete capsulorhexis. In 5 eyes with posterior capsule rupture, the posterior capsule occurred in 3 eyes during phacoemulsification, and injecting the lens cortex caused posterior capsule repture in 2 eyes; the IOL was implanted in the ciliary sulcus and the capsular bag in 4 and 1 eyes, respectively. Whether the consecutive capsulorhexis was successful ( χ2=4.286), whether the posterior capsule was ruptured ( χ2=5.455), whether the IOL was implanted in the capsular bag ( χ2=4.286), the differences in the number of eyes between the two groups were statistically significant ( P= 0.038, 0.020, 0.038). At the last follow-up, no special complications occurred. Conclusions:Intravitreal injection of TA combined with partial anterior PPV can improve the visibility of the anterior and posterior lens capsule and lens nucleus during phacoemulsification in patients with cataract and severe vitreous hemorrhage. The surgical success rate is high, the complications are few, and the safety is good.

OBJECTIVETo investigate the role of MT-ND1 m.3635G>A mutation in the pathogenesis of Leber's hereditary optic neuropathy (LHON).

METHODSBiochemical characteristics including the activity of complex Ⅰ, ATP production and oxygen consumption rate among lymphoblastoid cell lines derived from 3 carriers, 3 affected matrilineal relatives of the families and 3 controls were compared.

RESULTSComparison of mitochondrial functions in lymphoblastoid cell lines of the carriers, patients and controls showed a 51.0% decrease in the activity of complex Ⅰ in patients compared with controls (P<0.05). The m.3635G>A mutation has resulted in decreased efficiency of ATP synthesis (P<0.05). Comparison of oxygen consumption rate showed that the basal OCR (P<0.05), ATP-linked OCR (P<0.05) and the maximum OCR (P<0.05) have all reduced to some extent compared with the controls.

CONCLUSIONThese results showed that m.3635G>A, as a LHON-associated mutation, can lead to mitochondrial dysfunction.

Adenosine Triphosphate ; genetics ; Asian Continental Ancestry Group ; genetics ; Female ; Humans ; Male ; Mitochondria ; genetics ; Mutation ; genetics ; NADH Dehydrogenase ; genetics ; Optic Atrophy, Hereditary, Leber ; genetics ; Pedigree

OBJECTIVETo study the baseline distribution of polymorphisms in the promoter of peroxisome proliferators activated receptor co-activator 1 (PPARGC1A) gene in ethnic Hans from Beijing, and to assess their association with type 2 diabetes (T2DM).

METHODSA 2-stage study was designed. Firstly, the promoter region of PPAGC1A gene was screened with PCRRFLP in a small population (n=216, T2DM/control: 104/112), which was followed by a replication study of a larger group (n=1546, T2DM/control: 732/814). Fasting plasma glucose, insulin, blood lipid, height, weight, waist circumference, and blood pressure were measured in all subjects. Potential association was assessed by logistic regression. Linkage disequilibrium and haplotype analysis were conducted with Haploview software.

RESULTSFive polymorphisms were identified with Sanger sequencing, among which T-2120C (rs3755857), -1999C/G (rs2946386) and -1437T/C (rs2970870) were included for genotypic analysis based on their moderate levels of heterozygosity. No significant difference was found between the two groups. When adjusted for age and gender confounding, we have combined the OR values from population 1 and population 2 based on Mantel-Haenszel fixed model, and recognized a mild contribution of C allele of -1999C/G (rs2946386) to the 1.18-fold risk of T2DM (P=0.03, OR=118). No haplotype was associated with T2DM after permutation correction.

CONCLUSIONThe C allele of -1999C/G ( rs2946386) in the promoter region of the PPARGC1A gene is mildly associated with T2DM. Variations in the promoter region of the PPARGC1A gene seem not to confer the risk of T2DM in our population.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Blood Glucose ; metabolism ; Case-Control Studies ; China ; ethnology ; Diabetes Mellitus, Type 2 ; blood ; ethnology ; genetics ; Ethnic Groups ; genetics ; Female ; Genetic Variation ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Transcription Factors ; genetics

Objective To establish a method to validate the result of transcriptome sequencing using duplex PCR tech -nology combined with capillary electrophoresis .Methods According to a previous study on transcriptome sequencing , eight differentially expressed genes were chosen as target genes for examination .The mRNA expression level of these genes was detected using duplex PCR combined with agarose gel electrophoresis , duplex PCR combined with capillary electropho-resis and Q-PCR, respectively.Then, the verification efficiency of each method was evaluated carefully .Results The ver-ification efficiency of duplex PCR combined with agarose gel electrophoresis was 50%, while that of duplex PCR combined with capillary electrophoresis and Q-PCR was both 100%.Conclusion Combination of duplex PCR technology with capil-lary electrophoresis can be used as an alternative method to validate the results of transcriptome sequencing .

BACKGROUND:Posterior dislocation after total hip replacement is one of the most common complications that second only to loosen, and can affect the stability of the hip joint seriously. There is controversy on the effect of femoral head diameter and acetabular anteversion on the stability of hip joint in clinical study. OBJECTIVE:To investigate the effect of the femoral head diameter and acetabular anteversion on the stability of hip joint after hip prosthesis replacement. METHODS:The femoral head diameter and acetabular anteversion that affect the posterior instability after hip prosthesis replacement were measured on the cadaveric bone. The acetabular shel was inserted at 0°-20° of anteversion at five degree intervals. The femoral heads with different diameters (28, 32 and 36 mm) were used for experiment, the internal rotation degrees to dislocation caused by hip at 90° flexion and 0° adduction and at 90° flexion and 30° adduction were recorded. RESULTS AND CONCLUSION:When the cup anteversion varied from 0° to 15°, there was an increase in the degree of internal rotation angle that could cause hip dislocation with the increasing of femoral head diameter (P<0.05). When the cup anteversion varied from 15° to 20°, the increasing trend was not significant. With the hip at 90° flexion and 0° adduction, and the cup anteversion varied from 15° to 20°, the stability of 36 mm group was significantly higher than that of the 28 mm and 32 mm groups (P<0.01);the stability of 32 mm group was higher than that of 28 mm group when the acetabular anteversion in 10° or more (P<0.05);there was no significant difference in stability between groups when the anteversion less than 10°. With the hip at 90° flexion and 30° adduction, the stability of 36 mm group was significantly higher than that of the 28 mm and 32 mm groups (P<0.01);the stability of 32 mm group was higher than that of 28 mm group when the acetabular anteversion in 10° or more (P<0.05);there was no significant difference in stability between groups when the anteversion less than 10°. The results indicate that the increasing of acetabular anteversion can reduce the occurrence of dip dislocation, but when it is difficult to choice the acetabular anteversion, large-diameter femoral head is preferred to increase the stability of hip joint.

Objective To explore the correlation of high-sensitivity C-reactive protein (hs-CRP) with risk factors and target organ damage in hypertensive patients.Methods The levels of serum hs-CRP of 216 hypertensive cases (hypertension group) and 36 healthy subjects (control group) were tested and compared among different associated diseases, the number of involved target organ and the difference of involved target organ.The relativity between variables such as total cholesterol, high density lipoprotein cholesterol (HDL-C), left ventricular mass index (LVMI) and so on and hs-CRP was analyzed by linear correlation analysis and multiple linear regression analysis.Results The levels of serum hs-CRP in hypertension group were higher than those in control group[( 1.99 ± 0.34) mg/L vs.( 1.10 ± 0.26 ) mg/L](P ＜ 0.01 ).The levels of serum hs-CRP in hypertension combined with coronarv disease and hvoertension combined with diabetes mellitus[(2.39 ± 0.24), (2.10 ± 0.18 ) mg/L, respectively]were higher than those in simple hypertension[( 1.85 ± 0.30 ) mg/L], and the levels of serum hs-CRP in hypertension combined with coronary disease were higher than those in hypertension combined with diabetes mellitus, and there were significant difference (P ＜ 0.05 ).The levels of serum hs-CRP were positively correlated with the number of involved target organ (r =0.747,P ＜0.01 ).There were significant differences among different associated diseases.The levels of serum hs-CRP in hypertension combined with left ventricle thickening were higher than those in hypertension combined with carotid atherosclerosis, renal damage and diabetic retinopathy,and there were significant differences (P ＜ 0.05 ).There was no significant difference in the level of serum hs-CRP between hypertension combined with carotid atherosclerosis and hypertension combined with renal damage (P ＞ 0.05 ).Stepwise regression analysis showed that the dominating factors of the level of serum hs-CRP were LVMI, age and HDL-C, and the level of hs-CRP showed negative correlation with HDL-C.Conclusions The levels of serum hs-CRP in hypertensive patients are higher than those in healthy subjects.The more number of involved target organ, the higher levels of serum hs-CRP.Patients with different involved target organ have different inflammatory degree.The levels of serum hs-CRP in hypertension combined with coronary disease are higher than those in hypertension combined with diabetes mellitus.Stepwise regression analysis shows that the dominating factors for hs-CRP levels are LVMI, HDL-C and age.

Objective To investigate the effect of intensive lipid-lowering therapy on the imbalance between inflammatory and anti-inflammatory responses in patients with acute coronary syndrome (ACS).Methods Observed serum levels of hs-CRP and IL-IO in 82 patients with ACS, 17 patients with stable angina, and 22 controls. Forty-one patients with ACS were randomized to take either atorvastatin 10 mg/d (standard lipid-lowering therapy) or atorvastatin 40 mg/d (intensive lipid-lowering therapy) for one month in addition to their routine anti-anginal treatment. Serum levels of hs-CRP, blood lipids, IL-10 were investigat-ed.IL-10 was measured by ELISA. Results The level of hs-CRP in patients with ACS [(11.10 ± 14.30)mg/L] was higher than that in patients with stable angina [(2.47 ± 2.72) mg/L]and controls [(2.34 ± 4.22)mg/L] (P all < 0.05 ). The level of IL- 10 was lower in ACS patients [( 3.94 ± 1.91 ) ng/L] compared with those who had stable angina [(6.31 ± 4.26) ng/L] and controls [(7.76 ± 2.82) ng/L], Pan <0.05. The level of hs-CRP in patients with ACS was decreased and IL-10 was increased after one month treatment with atorvastatin (P < 0.05).The effect of atorvastatin 40 mg/d was more effective than that of atorvastatin 10 mg/d.Conclusions Patients with ACS have higher level of hs-CRP and lower level of IL-10 than those with sta-ble angina. This finding suggests that imbalance of inflammatory and anti-inflammatory responses is related with aggravation of atherosclerotic disease. Intensive lipid-lowering therapy is more effective than standard lipid-lowering therapy on ameliorating the imbalance.