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 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 explore the method of fertility preservation in severe β-thalassemia prepubertal boys who cannot produce sperm before gonadotoxicity therapy.Methods:Three cases of severe β-thalassemia patients who were going to undergo hematopoietic stem cell transplantation (HSCT) were reported. They were received testis cryopreservation by slow-rate freezing. The necessity of fertility preservation in prepubertal boys and the methods of fertility persevation, testicular cryopreservation and the downstream techniques were stated.Results:Totally 31, 31, 20 pieces of testicular tissue were frozen by slow-rate freezing in three boys respectively and the freezing process went smoothly.Conclusion:The cryopreservation of testicular tissue can preserve the fertility of severe β-thalassemia prepuberty boys who will receive HSCT, leaving hope for offspring.

Objective:To explore the method of fertility preservation in severe β-thalassemia prepubertal boys who cannot produce sperm before gonadotoxicity therapy.Methods:Three cases of severe β-thalassemia patients who were going to undergo hematopoietic stem cell transplantation (HSCT) were reported. They were received testis cryopreservation by slow-rate freezing. The necessity of fertility preservation in prepubertal boys and the methods of fertility persevation, testicular cryopreservation and the downstream techniques were stated.Results:Totally 31, 31, 20 pieces of testicular tissue were frozen by slow-rate freezing in three boys respectively and the freezing process went smoothly.Conclusion:The cryopreservation of testicular tissue can preserve the fertility of severe β-thalassemia prepuberty boys who will receive HSCT, leaving hope for offspring.

Objective:To explore the feasibility of autologous transplantation of frozen-thawed ovarian tissue to induce pubertal development in adolescent females.Methods:Before hematopoietic stem cell transplantation in patient with severe β-thalassemia, 11 pieces of ovarian tissue were frozen in the Center of Reproductive Medicine, the Sixth Affiliated Hospital of Sun Yat-sen University in 2019. The patient was diagnosed as premature ovarian failure after hematopoietic stem cell transplantation. There were no signs of puberty development and menarche. Orthotopic ovarian tissue transplantation was performed for the patient through laparoscopy, and a total of 5 pieces of ovarian tissue were transplanted on January 20, 2022. Postoperatively, we followed up the sex hormone levels, growth and development of the patients and menarche.Results:The patient developed menarche 5 months after ovarian transplantation. The levels of sex hormones showed that follicle-stimulating hormone and luteinizing hormone were significantly decreased, and estradiol levels were significantly increased, indicating that ovarian tissue transplantation was successful, and follicles had begun to recruit and develop. The patient's ultrasonography revealed a markedly enlarged uterus and a thickened endometrium. Antral follicles were detected in the left implantation site of pelvic cavity.Conclusion:Cryopreservation of ovarian tissue is recommended for fertility preservation in prepubertal children. Autologous frozen-thawed ovarian tissue transplantation can induce natural puberty development and restore the reproductive endocrine function in children with ovarian failure, delayed puberty development or even stagnation.

Objective:To explore the feasibility of autologous transplantation of frozen-thawed ovarian tissue to induce pubertal development in adolescent females.Methods:Before hematopoietic stem cell transplantation in patient with severe β-thalassemia, 11 pieces of ovarian tissue were frozen in the Center of Reproductive Medicine, the Sixth Affiliated Hospital of Sun Yat-sen University in 2019. The patient was diagnosed as premature ovarian failure after hematopoietic stem cell transplantation. There were no signs of puberty development and menarche. Orthotopic ovarian tissue transplantation was performed for the patient through laparoscopy, and a total of 5 pieces of ovarian tissue were transplanted on January 20, 2022. Postoperatively, we followed up the sex hormone levels, growth and development of the patients and menarche.Results:The patient developed menarche 5 months after ovarian transplantation. The levels of sex hormones showed that follicle-stimulating hormone and luteinizing hormone were significantly decreased, and estradiol levels were significantly increased, indicating that ovarian tissue transplantation was successful, and follicles had begun to recruit and develop. The patient's ultrasonography revealed a markedly enlarged uterus and a thickened endometrium. Antral follicles were detected in the left implantation site of pelvic cavity.Conclusion:Cryopreservation of ovarian tissue is recommended for fertility preservation in prepubertal children. Autologous frozen-thawed ovarian tissue transplantation can induce natural puberty development and restore the reproductive endocrine function in children with ovarian failure, delayed puberty development or even stagnation.

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.