Objective To investigate the protective effect of berberine (BBR) against ionizing radiation injury in rats and its mechanism of action. Methods Sprague-Dawley rats were divided into seven groups: normal control group, 1-Gy radiation group, 1-Gy radiation plus low-dose BBR (50 mg/kg) group, 1-Gy radiation plus high-dose BBR (150 mg/kg) group, 3-Gy radiation group, 3-Gy radiation plus low-dose BBR (50 mg/kg) group, and 3-Gy radiation plus high-dose BBR (150 mg/kg) group. All the groups except the normal control group were exposed to external irradiation with a medical electron linear accelerator, followed by BBR administration by gavage for consecutive ten days. The serum levels of superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA) were measured by using the micromethod. The pathological changes of the bone marrow and small intestine were observed with HE staining. Results Compared with the normal control group, the radiation groups showed significantly increased MDA levels (P < 0.05), significantly decreased SOD and GSH levels (P < 0.05), and more severe pathological damage of the bone marrow and small intestine. Compared with the radiation groups, the BBR groups showed significantly decreased MDA levels (P < 0.05), significantly increased SOD and GSH levels (P < 0.05), and reduced pathological damage to the bone marrow and small intestine, which were more marked in the high-dose BBR group. Conclusion BBR has a certain protective effect against radiation injury in rats, which may be through increasing the activity of antioxidant substances, enhancing free radical clearance, and thereby alleviating free radicals-caused oxidative damage.

Objective:To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury.Methods:This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded.Results:The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100–6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions:TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

Objective:To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury.Methods:This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded.Results:The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100–6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions:TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely

This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly (ADP-ribose) polymerase-1 (PARP1) and bromodomain containing protein 4 (BRD4), which had important cross relation in the global network of breast cancer, reflecting the synthetic lethal effect. A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragment-based combinatorial screening and activity assays that together led to the chemical optimization. Among these compounds, 19d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1, respectively. Compound 19d was further shown to efficiently modulate the expression of BRD4 and PARP1. Subsequently, compound 19d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase. Following pharmacokinetic studies, compound 19d showed its antitumor activity in breast cancer susceptibility gene 1/2 (BRCA1/2) wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight. These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.

The olfactory bulb (OB) is the first relay station in the olfactory system. In the OB, mitral/tufted cells (M/Ts), which are the main output neurons, play important roles in the processing and representation of odor information. Recent studies focusing on the function of M/Ts at the single-cell level in awake behaving mice have demonstrated that odor-evoked firing of single M/Ts displays transient/long-term plasticity during learning. Here, we tested whether the neural activity of M/Ts and sniffing patterns are dependent on anticipation and reward in awake behaving mice. We used an odor discrimination task combined with in vivo electrophysiological recordings in awake, head-fixed mice, and found that, while learning induced plasticity of spikes and beta oscillations during odor sampling, we also found plasticity of spikes, beta oscillation, sniffing pattern, and coherence between sniffing and theta oscillations during the periods of anticipation and/or reward. These results indicate that the activity of M/Ts plays important roles not only in odor representation but also in salience-related events such as anticipation and reward.

Objective: To investigate the effect and safety of intensive hyperthermia combined with low-dose cisplatin plus radiotherapy in the treatment of patients with locally advanced NSCLC. Methods: From January 2012 to December 2015, 104 patients with locally advanced NSCLC were chosen in the Second People's Hospital of Weifang and randomly divided into two groups according to the digital table, with 52 patients in each group.The control group was given low-dose cisplatin plus radiotherapy, and the observation group was given intensive hyperthermia on the basis of control group.The ORR, DCR, median OS, median PFS, KPS score, the levels of coagulation function index and tumor markers before and after treatment and incidence of side effects in the two groups were compared. Results: The DCR of the observation group was significantly higher than that of the control group(86.54% vs.69.23%, χ²=8.24, P<0.05). The median OS and median PFS of the observation group were significantly longer than those of the control group(11.9 months vs.8.3 months; 7.5 months vs.4.7 months, t=2.56, 3.01, P<0.05). The KPS scores after treatment of the observation group were significantly higher than those of the control group and before treatment[(75.49±8.94)points vs.(68.65±7.06)points; (75.49±8.94)points vs.(62.23±6.34)points, t=2.78, 5.11, all P<0.05]. The levels of coagulation function index and tumor markers after treatment of the observation group were significantly lower than those of the control group and before treatment(t=3.14, 2.67, 3.59, 7.31; 4.89, 4.02, 4.70, 9.21; 2.44, 2.60, 3.20; 3.15, 3.78, 4.06; all P<0.05). There was no statistically significant difference in the incidence of side effects between the two groups(P>0.05). Conclusion Intensive hyperthermia combined with low-dose cisplatin plus radiotherapy in the treatment of patients with locally advanced NSCLC can efficiently control disease progress, increase survival benefits, higher quality of life, improve coagulation function, reduce the levels of tumor markers and possess satisfactory safety.

AIM: To analyze the difference of endonuclease domain containing 1 (ENDOD1) expression be-tween benign prostatic hyperplasia ( BPH ) tissues and prostate cancer ( PCa ) tissues and to investigate the effect of ENDOD1 on the biological function of human prostate cancer cells .METHODS: The BPH samples ( n=20 ) and PCa samples (n=21) were processed and analyzed according to the instruction of immunohistochemical (IHC) staining.The mRNA and protein levels of ENDOD 1 in the normal prostate epithelial cells and prostate cancer cells were evaluated by RT -qPCR and Western blot , respectively .The recombinant plasmids pCMV-N-Flag-ENDOD1 was constructed and was trans-fected into the human prostate cancer cells .The proliferation , apoptosis , migration and invasion abilities of the prostate cancer cells were evaluated by MTT assay , flow cytometry, Transwell migration and Matrigel invasion assays , respectively. RESULTS:The analysis of variance of the immunoreactivity score showed that PCa tissues with high Gleason score dis -played significantly lower ENDOD1expression than that with low Gleason score and BPH (P<0.05).The expression of ENDOD1 at mRNA and protein levels in PC3 cells and DU145 cells was significantly lower than that in the LNCap cells (P<0.05).The proliferation of DU145 transfected with ENDOD1 was inhibited.The flow cytometry indicated that ENDOD1 over-expression in the DU145 cells resulted in a notable increase in G0/G1 phase arrest (P<0.05), but the ap-optotic rates showed no statistical difference .The results of Transwell assay showed that migration and invasion abilities of the cells were also inhibited after transfection with over-expressing ENDOD1 plasmid (P<0.05).CONCLUSION: The expression of ENDOD1 significantly decreased in prostate cancer with high Gleaon score .Meanwhile, the ENDOD1 is spe-cifically down-regulated in androgen independent prostate cancer (AIPC) cell lines.Over-expression of ENDOD1 remark-ably inhibits the proliferation , migration and invasion abilities of AIPC .

Objective The aim of this study was to evaluate the effect of marriage quality intervention in peer education model among women with breast cancer.Methods Marginal quality questionnaire was used to assess in the intervention and control groups during the perioperative period.There had 120 breast cancer patients in the intervention group and 135 normal subjects for control group.The patients were followed by the peer education model and the marriage and quality education during the chemotherapy period.The marriage quality questionnaires were carried out one year after the operation.Results Marital satisfaction(38.73±7.45),couples communication(38.12±7.03)and sex life(36.77±6.96)were significantly higher than those of the patients who participated in the traditional health education group after 1 year of operation.The control subjects with traditional health education had lower satisfaction of marital life(32.59±9.29),husband and wife communication(34.41±7.39)and sexual life(32.59±6.59)in one year after surgery(P<0.001).The scores of marital satisfaction,husband and wife communication,and sex scores were significantly lower in patients with traditional health education after 1 year of operation(P<0.001).Conclusion Marriage quality interventions in the peer education model can effectively affect the marital quality of postoperative patients with breast cancer.