Analysis of risk factors leading to anxiety and depression in patients with prostate cancer after castration and the construction of a risk prediction model.

BACKGROUND: Cancer patients often suffer from severe stress reactions psychologically, such as anxiety and depression. Prostate cancer (PC) is one of the common cancer types, with most patients diagnosed at advanced stages that cannot be treated by radical surgery and which are accompanied by complications such as bodily pain and bone metastasis. Therefore, attention should be given to the mental health status of PC patients as well as physical adverse events in the course of clinical treatment. AIM: To analyze the risk factors leading to anxiety and depression in PC patients after castration and build a risk prediction model. METHODS: A retrospective analysis was performed on the data of 120 PC cases treated in Xi'an People's Hospital between January 2019 and January 2022. The patient cohort was divided into a training group (n = 84) and a validation group (n = 36) at a ratio of 7:3. The patients' anxiety symptoms and depression levels were assessed 2 wk after surgery with the Self-Rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS), respectively. Logistic regression was used to analyze the risk factors affecting negative mood, and a risk prediction model was constructed. RESULTS: In the training group, 35 patients and 37 patients had an SAS score and an SDS score greater than or equal to 50, respectively. Based on the scores, we further subclassified patients into two groups: a bad mood group (n = 35) and an emotional stability group (n = 49). Multivariate logistic regression analysis showed that marital status, castration scheme, and postoperative Visual Analogue Scale (VAS) score were independent risk factors affecting a patient's bad mood (P < 0.05). In the training and validation groups, patients with adverse emotions exhibited significantly higher risk scores than emotionally stable patients (P < 0.0001). The area under the curve (AUC) of the risk prediction model for predicting bad mood in the training group was 0.743, the specificity was 70.96%, and the sensitivity was 66.03%, while in the validation group, the AUC, specificity, and sensitivity were 0.755, 66.67%, and 76.19%, respectively. The Hosmer-Lemeshow test showed a χ2 of 4.2856, a P value of 0.830, and a C-index of 0.773 (0.692-0.854). The calibration curve revealed that the predicted curve was basically consistent with the actual curve, and the calibration curve showed that the prediction model had good discrimination and accuracy. Decision curve analysis showed that the model had a high net profit. CONCLUSION: In PC patients, marital status, castration scheme, and postoperative pain (VAS) score are important factors affecting postoperative anxiety and depression. The logistic regression model can be used to successfully predict the risk of adverse psychological emotions.

[Correlation between adenoid hypertrophy, maxillary sinus mucosal thickening and dentofacial development in children].

PURPOSE：To investigate the effects of adenoid hypertrophy and maxillary sinus mucosal thickening on dentofacial development. METHODS：The selected subjects were divided into 4 groups according to the inclusion criteria: group A (adenoid hypertrophy with maxillary sinus mucosal thickening), group B (adenoid hypertrophy without maxillary sinus mucosal thickening), group C (normal adenoid with maxillary sinus mucosal thickening), and group D (normal adenoid without maxillary sinus mucosal thickening). There were 20 subjects in each group, aging from 12 to 14 years old. The volume of maxillary sinus was measured by Mimics software. The adenoid, dental arch width, basal bone width and palatal height were measured by Dolphin software and dentofacial measurements were performed in the lateral cephalograms derived from cone-beam CT (CBCT). The data were analyzed with SPSS 24.0 software package. RESULTS： There was no significant difference in dentofacial measurements between group B and group D or group C and group D，except for ANB angle (P<0.05). Compared with group D, SNB, ANB, Wits appraisal, NA-APo, MP-HP, N-Me, S-Go/N-Me, N-ANS (perp HP), sum of three angles, Ar-Go of group A were significantly different (P<0.05). Neither left nor right maxillary sinus bony volume had significant difference between group B and D or group C and D. CONCLUSIONS： Both adenoid hypertrophy and maxillary sinus mucosal thickening have impact on dentofacial development. Moderate or more severe adenoid hypertrophy with maxillary sinus mucosal thickening has greater impact on dentofacial development over adenoid hypertrophy or maxillary sinus mucosal thickening alone.

Inhibition of both EGFR and IGF1R sensitized prostate cancer cells to radiation by synergistic suppression of DNA homologous recombination repair.

Reduced sensitivity of prostate cancer (PC) cells to radiation therapy poses a significant challenge in the clinic. Activation of epidermal growth factor receptor (EGFR), type 1 insulin-like growth factor receptor (IGF1R), and crosstalk between these two signaling pathways have been implicated in the development of radiation resistance in PC. This study assessed the effects of targeting both receptors on the regulation of radio-sensitivity in PC cells. Specific inhibitors of EGFR and IGF1R, Erlotinib and AG1024, as well as siRNA targeting EGFR and IGF1R, were used to radio-sensitize PC cells. Our results showed that co-inhibiting both receptors significantly dampened cellular growth and DNA damage repair, and increased radio-sensitivity in PC cells. These effects were carried out through synergistic inhibition of homologous recombination-directed DNA repair (HRR), but not via inhibition of non-homologous end joining (NHEJ). Furthermore, the compromised HRR capacity was caused by reduced phosphorylation of insulin receptor substrate 1 (IRS1) and its subsequent interaction with Rad51. The synergistic effect of the EGFR and IGF1R inhibitors was also confirmed in nude mouse xenograft assay. This is the first study testing co-inhibiting EGFR and IGF1R signaling in the context of radio-sensitivity in PC and it may provide a promising adjuvant therapeutic approach to improve the outcome of PC patients to radiation treatment.

Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-κB/IKK pathway-induced apoptosis.

Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-κB pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-κB pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy.

[Expressions of RANK, RANKL, and osteoprotegerin in male rats at different ages].

OBJECTIVE: To investigate the expression of receptor activator of nuclear factor-κB (RANK), its ligand RANKL, and osteoprotegerin, and observe the effects of αD3 on their expressions in male rats at different ages. METHODS: Wistar rats at 6 weeks, 6 months, and 24 months (n=15) were examined for mRNA expressions of RANK/RANKL and osteoprotegerin in the left proximal femur using RT-PCR and for their protein expressions in the right femur using immunohistochemistry. RANK/RANKL and osteoprotegerin expressions were also detected in another 15 rats aged 24 months following intragastric administration of 0.05 µg/kg αD3 (3 times a week for 10 weeks). RESULTS: Compared with 6-week-old rats, 6-month- and 24-month-old rats showed a 6.2-fold and 7.3-fold increase of RANKL mRNA expression, respectively (P<0.05), and osteoprotegerin mRNA levels increased slightly with age. αD3 treatment resulted in significantly increased expression of RANK in 24-month-old rats with a lowered RANKL/osteoprotegerin ratio. RANKL and osteoprotegerin were co-localized in the osteoblasts and chondrocytes. αD3 treatment also caused an increased expression of osteoprotegerin mRNA in 24-month-old rats. CONCLUSION: The age-related increase of the ratio of RANKL/osteoprotegerin mRNA promotes osteoclast activity and bone turnover. αD3 has favorable effect on osteogenesis and suppress bone absorption in the femur possibly by reducing RANK expression and lowering RANKL/osteoprotegerin ratio.