Dosimetric risk factors for radiation esophagitis in patients with breast cancer following regional nodal radiation.

BACKGROUND: Radiation esophagitis (RE) is one of the most common clinical symptoms of regi-onal lymph node radiotherapy for breast cancer. However, there are fewer studies focusing on RE caused by hypofractionated radiotherapy (HFRT). AIM: To analyze the clinical and dosimetric factors that contribute to the development of RE in patients with breast cancer treated with HFRT of regional lymph nodes. METHODS: Between January and December 2022, we retrospectively analysed 64 patients with breast cancer who met our inclusion criteria underwent regional nodal intensity-modulated radiotherapy at a radiotherapy dose of 43.5 Gy/15F. RESULTS: Of the 64 patients in this study, 24 (37.5%) did not develop RE, 29 (45.3%) developed grade 1 RE (G1RE), 11 (17.2%) developed grade 2 RE (G2RE), and none developed grade 3 RE or higher. Our univariable logistic regression analysis found G2RE to be significantly correlated with the maximum dose, mean dose, relative volume 20-40, and absolute volume (AV) 20-40. Our stepwise linear regression analyses found AV30 and AV35 to be significantly associated with G2RE (P < 0.001). The optimal threshold for AV30 was 2.39 mL [area under the curve (AUC): 0.996; sensitivity: 90.9%; specificity: 91.1%]. The optimal threshold for AV35 was 0.71 mL (AUC: 0.932; sensitivity: 90.9%; specificity: 83.9%). CONCLUSION: AV30 and AV35 were significantly associated with G2RE. The thresholds for AV30 and AV35 should be limited to 2.39 mL and 0.71 mL, respectively.

Dynamic changes and correlation between symptoms and quality of life in patients with breast cancer during chemotherapy.

BACKGROUND: Standardized chemotherapy for breast cancer can improve the survival of patients, but during the process, it is accompanied by a variety of symptoms. OBJECTIVE: To explore the dynamic changes of symptoms and quality of life in breast cancer patients at different time points during chemotherapy, and to explore the correlation with quality of life. METHOD: A prospective study method was used to collect 120 breast cancer patients undergoing chemotherapy as the research objects. The general information questionnaire, the Chinese version of the M.D. Anderson Symptom inventory (MDASI-C), and the European Organization for Cancer Research and Treatment (EORTC) Quality of Life questionnaire were used in the first week (T1), first month (T2), three month (T3) and 6 months after chemotherapy (T4) to conduct dynamic investigation. RESULTS: The symptoms of breast cancer patients at four time points during chemotherapy period were: psychological symptoms, pain-related symptoms, perimenopausal symptoms, impaired self-image, and neurological related symptoms etc. At T1, it exhibited 2 symptoms, however as moving along the chemotherapy process, the symptoms are increasing. The severity is (F= 76.32, P< 0.001), life of quality (F= 117.64, P< 0.001) vary. At T3, there were 5 symptoms, and at T4 symptom number increased to 6 with worsening quality of life. It exhibited positive correlation with scores in multiple domains of quality of life (P< 0.05), and the above symptoms showed positive correlation with multiple domains of QLQ-C30 (P< 0.05). CONCLUSION: After T1-T3 of chemotherapy in breast cancer patients, the symptoms become more serious and the quality of life reduced. Therefore, medical staff should pay attention to the occurrence and development of patient's symptoms, create a reasonable plan from the perspective of symptom management and carry out personalized interventions to improve patient's quality of life.

TMEM16F may be a new therapeutic target for Alzheimer's disease.

TMEM16F is involved in many physiological processes such as blood coagulation, cell membrane fusion and bone mineralization. Activation of TMEM16F has been studied in various central nervous system diseases. High TMEM16F level has been also found to participate in microglial phagocytosis and transformation. Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer's disease. However, few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer's disease. In this study, we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD. We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome. Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice. After TMEM16F knockdown in mice, spatial memory ability was improved, microglia polarization to the M2 phenotype was promoted, NLRP3 inflammasome activation was inhibited, cell apoptosis and Aß plaque deposition in brain tissue were reduced, and brain injury was alleviated. We used amyloid-beta (Aß25-35) to stimulate human microglia to construct microglia models of Alzheimer's disease. The levels of TMEM16F, inducible nitric oxide synthase (iNOS), proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aß25-35 treated group compared with that in the control group. TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3, reduced the release of proinflammatory factors interleukin-1, interleukin-6 and tumor necrosis factor-α, and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1ß and interleukin-18. This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin. Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer's disease through participating in polarization of microglia and activation of the NLRP3 inflammasome. These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer's disease treatment.

Long-term efficacy, prognostic factors, and safety of deep brain stimulation in patients with refractory Tourette syndrome: A single center, single target, retrospective study.

BACKGROUND: To evaluate the long-term efficacy, prognostic factors, and safety of posteroventral globus pallidus internus deep brain stimulation (DBS) in patients with refractory Tourette syndrome (RTS). METHODS: This retrospective study recruited 61 patients with RTS who underwent posteroventral globus pallidus internus (GPi) DBS from January 2010 to December 2020 at the Chinese People's Liberation Army General Hospital. The Yale Global Tic Severity Scale (YGTSS), Yale-Brown Obsessive-Compulsive Scale (YBOCS), Beck Depression Inventory (BDI), Gilles de la Tourette Syndrome Quality-of-Life Scale (GTS-QOL) were used to evaluate the preoperative and postoperative clinical condition in all patients. Prognostic factors and adverse events following surgery were analyzed. RESULTS: Patient follow up was conducted for an average of 73.33 ± 28.44 months. The final postoperative YGTSS (32.39 ± 22.34 vs 76.61 ± 17.07), YBOCS (11.26 ± 5.57 vs 18.31 ± 8.55), BDI (14.36 ± 8.16 vs 24.79 ± 11.03) and GTS-QOL (39.69 ± 18.29 vs 78.08 ± 14.52) scores at the end of the follow-up period were significantly lower than those before the surgery (p < 0.05). While age and the duration of follow-up were closely related to prognosis, the disease duration and gender were not. No serious adverse events were observed and only one patient exhibited symptomatic deterioration. CONCLUSIONS: Posteroventral-GPI DBS provides long-term effectiveness, acceptable safety and can improve the quality of life in RTS patients. Moreover, DBS is more successful among younger patients and with longer treatment duration.

PPAR-α Agonist GW7647 Protects Against Oxidative Stress and Iron Deposit via GPx4 in a Transgenic Mouse Model of Alzheimer's Diseases.

Alzheimer's disease (AD) is a neurodegenerative disease caused by lipid peroxidation and iron hemostasis of the brain. PPAR-α is regarded as the most encouraging therapeutic approach of several neurodegenerative and metabolic disorders, due to its potent regulatory effects. In this study, we examined the ameliorative effect and the mechanisms of a PPAR-α agonist, GW7647, on the established AD models using APP/PS1 mice and APPsw/SH-SY5Y cells. Through Aß quantification and behavioral test, we found that GW7647 reduced Aß burden and improved cognitive defect in APP/PS1 mice. Liquid chromatography-mass spectrometry analysis indicated that GW7647 could enter the brain after oral administration. Neuronal cell death and iron deposit were inhibited, accompanied by decreased lipid peroxidation and inflammation. In an in vitro study of APPsw cells, we found that PPAR-α directly bound with GPx4 intron3 to promote GPx4 transcription and reduced the iron transport capability. Our data suggested that activation of PPAR-α by GW7647 improved the disruption of iron homeostasis in the brain of APP/PS1 mice and alleviated neuronal inflammation and lipid peroxidation, which was possibly related to the upregulated transcription of GPx4 mediated by the interaction of GPx4 noncoding region and the PPAR-α.

Methylene Blue Exerts Anticonvulsant and Neuroprotective Effects on Self-Sustaining Status Epilepticus (SSSE) Induced by Prolonged Basolateral Amygdala Stimulation in Wistar Rats.

BACKGROUND This study was designed to investigate the potential anticonvulsant and neuroprotective effects of methylene blue (MB) on self-sustaining status epilepticus (SSSE) induced by prolonged basolateral amygdala stimulation (BLA) in Wistar rats. MATERIAL AND METHODS The rats were randomly divided into 4 groups: (1) the Control group (rats without any treatment); (2) the Sham group (rats received electrode implantation but without electrical stimulation); (3) the SSSE group (rats received electrode implantation and additional electrical stimulation); and (4) the SSSE+MB group (rats received 1 mg/kg MB intraperitoneal injection 5 min after SSSE). SSSE models were established by prolonged BLA stimulation. The severities of SSSE were assessed by the number of separate seizures and the accumulated time of seizures. The variations of malondialdehyde/glutathione (MDA/GSH) were assessed 24 h after the establishment of SSSE. Nissl staining was performed to detect the surviving neurons in hippocampal CA1 and CA3 regions, and Western blotting assays were used to detect Caspase-3 (CASP3), B cell lymphoma 2 (BCL2), and BCL2-associated X protein (BAX). RESULTS Compared with the SSSE group, treatment with MB (1) markedly reduced the number and accumulated time of seizure activities; (2) significantly attenuated the increase of MDA and the decrease of GSH hippocampal levels; (3) markedly improved the cell morphology and alleviated the neuronal loss in hippocampal CA1 and CA3 regions; (4) significantly attenuated the increase of CASP3 and BAX and the decrease of BCL2 hippocampal levels. CONCLUSIONS MB has a protective effect in the SSSE model and may be useful as an adjuvant for preventing or treating epilepsy in humans.

Downregulation of ZMYND11 induced by miR-196a-5p promotes the progression and growth of GBM.

ZMYND11 (zinc finger MYND-type containing 11) has been widely regarded to be involved in a variety of cancers as a potential suppressor. However, the biological role and mechanism of ZMYND11 in glioblastoma multiform (GBM) remain unknown. In this study, we found that ZMYND11 expression was remarkably decreased in GBM tissues from 20 cases and cell line (U87) compared to normal brain tissue from 10 cases (P < 0.001). Furthermore, we explored that ZMYND11 upregulation significantly suppressed U87 cells proliferation and invasion, induced cell cycle arrest and apoptosis in vitro. Subsequently, we identified increased ZMYND11 inhibited the tumor growth using tumor cells xenograft experiment on rude mice. Moreover, we explored that ZMYND11 was a new direct and functional target of miR-196a-5p in U87 via luciferase reporter assay. In addition, we confirmed the negative correlation between miR-196a-5p and ZMYND11 in GBM tissue and U87 cells by changing the expression level of miR-196a-5p with lentivirus and plasmid vector. Furthermore, we demonstrated that decreased ZMYND11 could reverse suppressive effect of downregulated miR-196a-5p on U87 by rescue experiment. Taken together, ZMYND11 was demonstrated to be a potential and extremely promising suppressor of GBM, while miRNA-196a-5p was quite an important target of treatment of GBM.

Correlations of VDR and VDBP genetic polymorphisms with susceptibility to adolescent idiopathic scoliosis and efficacy of brace treatment.

OBJECTIVE: This paper aimed to elucidate the correlations of VDR and VDBP polymorphisms with susceptibility to adolescent idiopathic scoliosis (AIS) and efficacy of brace treatment. METHODS: AIS patients and healthy controls were enrolled. Lumbar spine bone mineral density (LSBMD) and femoral neck bone mineral density (FNBMD) were detected by dual energy X-ray absorptiometry. VDR and VDBP polymorphisms were detected by PCR-RFLP. Efficacy of brace treatment was evaluated by Cobb measurement. RESULTS: The frequencies of Bsm I Bb genotype and B allele, and rs222020 CC genotype and C allele in the AIS patients were higher than in the controls. After treatment, the correction rates of average Cobb angle, AVT, AVR and TS in patients with Bsm I Bb and VDBP rs222020 CC genotypes were relatively low. CONCLUSION: VDR Bsm I and VDBP rs222020 C>T polymorphisms may be predisposition factors of AIS and the efficacy of brace treatment in AIS patients.

Therapeutic potential of human umbilical cord blood mesenchymal stem cells on erectile function in rats with cavernous nerve injury.

OBJECTIVE: To evaluate the therapeutic potential of human umbilical cord blood mesenchymal stem cells (hUCBMSCs) on promoting erectile function in a rat model of bilateral cavernous nerve (CN) crush injury. RESULTS: Fifty male Sprague-Dawley rats were randomly assigned to sham + PBS group (n = 10), BCNI (bilateral cavernous nerve crush injury) + PBS group (n = 10), BCNI + hUCBMSCs group (n = 30). At day 28 (n = 10) post-surgery, erectile function was examined and histological specimens were harvested. Compared with BCNI + PBS group, hUCBMSC intracavernous injection treatment significantly increased the mean ratio of ICP/MAP, nNOS-positive nerve fibers in the dorsal penile nerve, smooth muscle content, and smooth muscle to collagen ratio in the corpus cavernousum. Electron microscopy revealed few CN and major pelvic ganglion (MPG) lesions in the BCNI + hUCBMSCs group. Injected hUCBMSCs were localized to the sinusoid endothelium of the penis and MPG on day 1, 3, 7, and 28 post-intracavernous injection. CONCLUSION: hUCBMSCs intracavernous injection treatment improves erectile function by inhibiting corpus cavernosum fibrosis and exerting neuroregenerative effects on cell bodies of injured nerves at MPG in a BCNI rat model.

[Transurethral seminal vesiculoscopy combined with finasteride for recurrent hematospermia].

OBJECTIVE: To evaluate the clinical effectiveness of transurethral seminal vesiculoscopy (TUSV) combined with finasteride in the treatment of recurrent hemospermia. METHODS: This study included 32 patients with recurrent hematospermia, with the disease course of 3 months to 4 years. After administration of finasteride at 5 mg/d for 2 weeks, the patients underwent TUSV for both exploration of the causes and treatment, followed by medication with finasteride at the same dose for another 2 weeks. Postoperative follow-up was conducted for observation of the outcomes and complications. RESULTS: TUSV was successfully accomplished in all the 32 cases, which revealed 16 cases of seminal vesiculitis, 10 seminal calculi, 1 seminal vesicle cyst, 2 seminal vesicle polyps, and 3 seminal vesicle abscess. The operative time was 20 to 51 (31.0 +/- 5.2) minutes. Postoperative complications included 1 case of acute epididymitis and 3 cases of breast discomfort within the first 4 weeks. No incontinence, urethral stricture, rectal injury, retrograde ejaculation, and sexual dysfunction occurred postoperatively. All the patients but 1 were followed up for 6 months to 2 years. Twenty-nine of the cases were cured, and 2 experienced recurrence. CONCLUSION: Transurethral seminal vesiculoscopy combined with finasteride is safe and effective for the treatment of recurrent hemospermia.

[Serotype distribution of non-polio enterovirus in patients with acute flaccid paralysis during 2011-2012 in Hebei Province, China].

This study aims to investigate the serotype distribution of non-polio enterovirus (NPEV) isolated from patients with acute flaccid paralysis (AFP) during 2011-2012 in Hebei Province, China and to analyze the relationship between these viruses and AFP. NPEV strains were isolated from the stool specimens from AFP cases in Hebei using human rhabdomyosarcoma cells (RD) and the mouse cell line expressing the gene for the human cellular receptor for poliovirus (L20B) according to the WHO requirements. The nucleotide sequence of VP1 region was determined, and the serotypes of NPEV were identified by molecular typing. The results showed that among the 82 strains of NPEV isolated from the AFP cases during 2011-2012, 42 isolates (55.3%) were identified as human enterovirus A (HEV-A), which were classified into 4 serotypes, 34 (44.7%) as human enterovirus B (HEV-B), which were classified into 13 serotypes, 2 as adenovirus, and 4 were untyped; human enteroviruses C and D were not found in these cases. Enterovirus A71 (EV-A71) was the main type of HEV-A, accounting for 85.7% of all HEV-A strains. HEV-A, especially EV-A71, was predominant among the NPEV strains isolated from AFP patients during 2011-2012 in Hebei Province.

Electrocautery-induced cavernous nerve injury in rats that mimics radical prostatectomy in humans.

OBJECTIVE: To investigate the early and delayed effects of cavernous nerve electrocautery injury (CNEI) in a rat model, with the expectation that this model could be used to test rehabilitation therapies for erectile dysfunction (ED) after radical prostatectomy (RP). MATERIALS AND METHODS: In all, 30 male Sprague-Dawley rats were randomly divided equally into two groups (15 per group). The control group received CNs exposure surgery only and the experimental group received bilateral CNEI. At 1, 4 and 16 weeks after surgery (five rats at each time point), the ratio of maximal intracavernosal pressure (ICP) to mean arterial pressure (MAP) was measured in the two groups. Neurofilament expression in the dorsal penile nerves was assessed by immunofluorescent staining and Masson's trichrome staining was used to assess the smooth muscle to collagen ratio in both groups. RESULTS: At the 1-week follow-up, the mean ICP/MAP was significantly lower in the CNEI group compared with the control group, at 9.94% vs 70.06% (P < 0.05). The mean ICP/MAP in the CNEI group was substantially increased at the 4- (35.97%) and 16-week (37.11%) follow-ups compared with the 1-week follow-up (P < 0.05). At all three follow-up time points, the CNEI group had significantly decreased neurofilament staining compared with the control group (P < 0.05). Also, neurofilament expressions in the CNEI group at both 4 and 16 weeks were significantly higher than that at 1 week (P < 0.05), but there was no difference between 4 and 16 weeks (P > 0.05). The smooth muscle to collagen ratio in the CNEI group was significantly lower than in the control group at the 4- and 16-week follow-ups (P < 0.05), and the ratio at 16 weeks was further reduced compared with that at 4 weeks (P < 0.05). CONCLUSIONS: In the CNEI rat model, we found the damaging effects of CNEI were accompanied by a decline in ICP, reduced numbers of nerve fibres in the dorsal penile nerve, and exacerbated fibrosis in the corpus cavernosum. This may provide a basis for studying potential preventative measures or treatment strategies to ameliorate ED caused by CNEI during RP.