The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Purpose: Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. Materials and Methods: We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. Results: We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

ObjectiveTo establish a more accurate and sensitive liquid chromatography-ultraviolet (LC-UV) method for the determination of uric acid in rat serum, and compare the results with those of commercial kits, providing a new method for the accurate determination of uric acid in the rat hyperuricemia model induced by potassium oxonate.Methods A hyperuricemia model was established by intraperitoneal injection of potassium oxonate (300 mg/kg) into SPF-grade male SD rats, and the control group was administered an equal amount of 0.5% sodium carboxymethylcellulose solution. Blood samples were collected from the posterior orbital venous plexus and centrifuged to obtain serum samples. After precipitation with 0.1% trifluoroacetic acid-acetonitrile (containing the internal standard 3,4-dihydroxybenzylamine hydrobromide), the supernatant was injected for analysis. Uric acid was separated on a Waters XBridge HILIC column (150 mm×4.6 mm, 3.5 μm) using acetonitrile (containing 0.5% formic acid and 2 mmol/mL ammonium formate) as the organic phase and methanol solution (methanol∶water=1∶1, containing 0.5% formic acid with 2 mmol/L ammonium formate) as the aqueous phase for isocratic elution and detection at 290 nm. Serum samples treated with activated carbon were used as substitute matrices for the methodological verification. Serum uric acid levels in rats with potassium oxonate-induced hyperuricemia were measured using the established LC-UV method and commercially available kits (uricase and phosphotungstic acid methods), and the accuracies of the three methods were compared.Results Serum uric acid showed a good linear relationship (R>0.999) at mass concentration of 10–200 μg/mL in rats, the lower limit of quantification was 10 μg/mL, the accuracy ranged from -2.17% to 2.21%, the intra-batch precision ranged from 0.52% to 1.95%, the inter-batch precision ranged from 3.04% to 4.90%, and the extraction recovery ranged from 83.12% to 89.91%. In the rat model, the results obtained using the commercially available phosphotungstic acid method kit were significantly higher than those of the LC-UV method, and those obtained using the commercially available uricase method kit were significantly lower than those of the LC-UV method, but the LC-UV method showed the best recovery of the spiked sample (95.90%–99.96%).ConclusionThe LC-UV method developed in this study can determine the concentration of uric acid in rat serum with higher accuracy than commercially available kits and is recommended for the determination of serum uric acid in the rat model of hyperuricemia induced by potassium oxonate.

BACKGROUND: To investigate the correlation between the reduction of lung volume and the degree of lung function damage after lobectomy. METHODS: A total of 131 patients (72 males and 59 females) who underwent thoracoscopic lobectomy in the First Affiliated Hospital of Suzhou University from January 2019 to July 2020 (including thoracoscopic resection of left upper lobe, left lower lobe, right upper lobe, right middle lobe and right lower lobe). In order to compare the difference between postoperative pulmonary function and preoperative pulmonary function, the pulmonary function measurements were recorded at 7 days before operation, and 3 months, 6 months and 1 year after operation. Forced expiratory volume in 1 second (FEV1) was used as the main evaluation parameter of pulmonary function. The original lung volume and the remaining lung volume at each stage were calculated by Mimics Research 19.0 software. The correlation between lung volume and lung function was analyzed. RESULTS: FEV1 in postoperative patients was lower than that before operation, and the degree of decline was positively correlated with the resection volume of lung lobes (the maximum value was shown in the left lower lobe group). Significantly, there was no significant difference in the degree of pulmonary function reduction between 3 months, 6 months and 1 year after operation. CONCLUSIONS The decrease of lung tissue volume after lobectomy is the main reason for the decrease of lung function, especially in the left lower lobe. And 3 months after lobectomy can be selected as the evaluation node of residual lung function.
Carcinoma, Non-Small-Cell Lung/surgery* ; Female ; Forced Expiratory Volume ; Humans ; Lung/surgery* ; Lung Neoplasms/surgery* ; Male ; Pneumonectomy/adverse effects* ; Respiratory Function Tests

Duchene muscular dystrophy (DMD) is a serious progressive muscular dystrophy.Reports in recent years about abnormal lipid in DMD patients have increased, yet little attention has been paid to liver lipid.This study aimed to explore the effect of dystrophin gene defect on liver lipid synthesis.7-week-old mdx male mice were used as DMD model.The conditions of liver function, liver lipid accumulation and liver lipid synthesis were determined through liver tissue morphological examination, blood biochemical examination, and detection of hepatic gene and protein expression.The results showed that lipid droplets in liver of mdx mice increased significantly.The contents of total cholesterol and triglyceride in liver, aspartate aminotransferase and alanine aminotransferase in serum increased.The gene and protein expression of hepatic lipid synthesis-related enzymes such as fatty acid synthase, acetyl CoA carboxylase, and sterol regulatory element binding protein 1-c were up-regulated.These results showed accumulation of liver lipid in 7-week-old mdx male mice.

Objective：To analyze the expression and clinic significance of activity-dependent neuroprotective protein (ADNP) in bladder urothelial carcinoma. Methods: A total of 28 pairs of bladder cancer tissues and corresponding adjacent normal tissuesthat surgically resected at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from June 1, 2019 to July 15, 2019 were collected for this study. The mRNAexpression ofADNP in 20 pairs of tissue samples was detected by qPCR, and the protein expressionin the other 8 pairs was detected by WB. Mean while, the clinicopathological data of patients with bladder urothelial carcinoma treated in our hospital from January 1, 2005 to December 31, 2007 were retrospectively analyzed; and the expression of ADNP in the corresponding paraffin tumor sections were determined with immunohistochemical staining, and normal bladder tissue sections from patients who underwent surgery for other bladder diseases during the same period were collected for comparison. Chi-square test was used to analyze the correlation between ADNP expression and different clinicopathological features, Kaplan-Meier method was used for survival analysis, and Cox risk regression model was used forunivariate and multivariate analysis of prognosticfactors. Results: ThetranscriptionalandtranslationallevelsofADNPincancertissues were higher than those in adjacent normal tissues (all P<0.05), and the expression level ofADNP was correlated with the histological grade, clinical stages and survival status of patients with bladder cancer (P<0.05). Of all the 221 patients included in the study, 32 patients lost to follow-up,and patients with high ADNP expression had

Objective To investigate the effect of complement C3a on mouse podocytes phenotype transformation.Methods Purified C3a recombinant protein was used to stimulate mature mouse podocytes.The expression of the mature podocyte markers synaptopodin,podocin,nephrin,CD2-associated protein (CD2AP) and the mesenchymal cell markers fibroblast specific protein 1 (FSP-1),α-smooth muscle actin (α-SMA) were detected by RT-PCR,Western blotting,immunochemistry and immunofluorescence,respectively.Some podocytes were transfected with integrin-linked kinase (ILK) siRNA before the administration of C3a,the expression of nephrin and α-SMA were accessed by Western blotting,and the expression of Snail and α-actinin 4 were accessed by Western blotting and immunochemical method.The migration ability of podocytes was observed by scratch test.Results Immunocytochemistry and immunofluorescence analysis showed that synaptopodin,podocin,nephrin,CD2AP were highly expressed by mature mouse podocytes.The expression of these podocyte markers could be markedly inhibited after 24 h of C3a (0.1 μmol/L) treatment,and accompanied by the induction of mesenchymal markers FSP-1 and α-SMA.Compared with control group,the mRNA levels of synaptopodin,podocin,CD2AP and nephrin were significantly repressed by the administration of C3a in a dose-dependent manner,whereas the transcription of FSP-1 and α-SMA were remarkably up-regulated by C3a treatment (P ＜ 0.05,respectively).Western blotting analysis also confirmed the decrease of synaptopodin,podocin,nephrin and CD2AP protein and the increase of FSP-1 and α-SMA protein were closely depend on the C3a concentration (P ＜ 0.05,respectively).To further assess the downstream of C3a,some podocytes were transfected with ILK siRNA before the administration of C3a.Compared with C3a group,the protein levels of nephrin and α-SMA were significantly changed by the administration of ILK siRNA (P ＜ 0.05,respectively).The expression of α-actinin 4 and Snail induced by C3a were inhibited by ILK knockdown (P ＜ 0.05,respectively),accompanied by a decline of cell migration potency.Conclusion Complement fragment C3a can induce transformation of mouse podocytes to mesenehymal cells,and ILK signaling pathway is involved in this cell type transformation.

Objective To evaluate and compare the analytical performances and application values of three nucleic acid extraction methods for quantification of plasma Epstein-Barr Virus ( EBV ) DNA. Methods It used silica membrane spin column , boiling and automated magnetic bead method to extract viral nucleic acid in parallel , and combined real-time fluorescence quantitative PCR assays for quantitative EBV-DNA quantification.The performances of three methods were determined and compared by using the third-party reference materials , and the clinical values were analyzed by pairing detecting 100 NPC patients and 100 healthy subjects in pair .Results The accuracy and imprecision of three methods were all in line with requirements , and the results of clinical samples were linearly correlated . But actually the reproducibility and intermediate imprecision of the magnetic bead method were smaller and stable than those of the spin column method and the boiling method ( all <3％);the limit of detection for the magnetic bead method was 3.334 ×101 IU/ml, better than that of spin column method (4.159 ×101 IU/ml) and boiling method (8.511 ×101 IU/ml);the linear range of the magnetic bead method was 5.4 ×101 -5.4 ×105 IU/ml, slightly wider than that of the boiling method (5.4 ×102 -5.4 ×105 IU/ml); the ability of anti -Hb interference ability of magnetic bead method is better than that of boiling method ;and the positive rate and the mean viral load of the NPC samples measured with the magnetic bead method were significantly higher (95％, 8.342 ×103 IU/ml) than those measured with the spin column method (84％, 4.707 ×103 IU/ml) and the boiling method (78％, 2.571 ×103 IU/ml) ( P all<0.05).Conclusion The automated magnetic bead nucleic acid extraction method offered better analytical performance and higher clinical value for EBV DNA quantification in plasma .

To observe the effects of emodin ( Emo) on acute fatty liver in mice induced by DL-ethionine ( DL-Eth) or tetracyclin ( Tetra) and its potential mechanism, ICR mice of acute fatty liver model induced by DL-Eth were orally administered with Emo or positive control, ursodeoxycholic acid ( UDCA) for 7 days. On day 7, except that the control and Emo groups were treated with vehicle control, animals were orally administered with DL-Eth to induce acute fatty liver model. ICR mice of acute fatty liver model induced by Tetra were orally administered with Emo or positive control, Dong Bao Gan Tai ( DB) or total flavonoid C-glycosides from Abrus mollis extract ( AME) for 7 days. From day 4, except that the control group was treated with vehicle control, animals were injec-ted with Tetra intraperitoneally for 4 days to induce acute fatty liver model. Liver histopathological analyses were determined by HE staining. Serum aspartate transaminase ( AST) , alanine transaminase ( ALT) , serum triglyceride ( TG) , hepatic TG and hepatic total cholesteol ( TC) were detected. The expression of phosphorylated AMP-activa-ted kinase ( p-AMPK) , phosphorylated acetyl-CoA carboxylase ( p-ACC) , SREBP1 and fatty acid synthase ( FAS) were determined by Western blot. The expression of fatty acid translocase ( CD36 ) , peroxisome proliferator activa-ted receptor alpha ( PPARα) and microsomal triglyceride transfer protein ( MTTP ) in liver were determined by RT-PCR. Compared with model groups, Emo could improve hepatocyte swelling and hepatic steatosis induced by DL-Eth or Tetra. Serum AST, ALT, serum TG, hepatic TG and hepatic TC were decreased by Emo significantly. DL-Eth-induced increase of fatty acid synthetase-associated protein was down-regulated by Emo. Fatty acid uptake was down-regulated by Emo; fatty acid oxidation and secretion were increased by Emo. Emo might be effective in preventing acute fatty liver in mice induced by DL-Eth or Tetra.