1.Effect of Electricity Targeting TGF-β 1/smads Signaling in Oligoasthenthymic Rats
Chunxue MENG ; Fei WANG ; Wenjing SUN ; Nan YANG ; Hailong ZHAO ; Shengfu ZHANG ; Huisheng MA ; Bin GUO
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(5):797-805
[Objective]To explore the effects of electricity on sperm quality,sex hormone levels,and related proteins in TGF-β 1/smads signaling in testicular tissue.[Methods]Forty male SD rats were randomly divided into blank group,model group,electroacupuncture group,and positive drug group.Adenine gavage method was used to establish the model,in the electroacupuncture group,rats received electroacupuncture treatment at the acupoints Zhongji,Guanyuan,Zusanli,and Sanyinjiao once daily for 30 minutes;in the positive drug group,rats were administered L-carnitine oral solution via gavage at a dosage of 10 mL/kg,both intervention groups underwent continuous treatment for 28 days.After treatment,the changes of sperm number,sperm motility rate,follicle-stimulating hormone(FSH),luteizing hormone(LH)and serum sex hormone testosterone(T)were detected by HE staining,and the expression of TGF-β-1/smads signaling pathway in testicular tissue was examined by Western Blot.[Results]Compared to the blank group,the model group showed a significant decrease in sperm count and sperm motility rate(P<0.05),both the electroacupuncture group and the positive drug group exhibited significant increases compared to the model group(P<0.05).Compared to the blank group,the model group had a significant decrease in serum testosterone(T)levels(P<0.05),and significant increases in serum FSH and LH levels(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant increases in serum T levels(P<0.05),and significant decreases in serum FSH and LH levels(P<0.05).The HE staining results showed typical pathological features of AR in the testicular tissue of model group rats,with varying degrees of improvement observed in electroacupuncture and positive drug group rats.Western Blot analysis revealed that in the model group,the protein levels of TGF-β,p-smad2,and p-smad3 in the TGF-β1/smads pathway in testicular tissue were significantly increased(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant decreases in the protein levels of TGF-β,p-smad2,and p-smad3(P<0.05).[Conclusion]Acupuncture can improve the sperm number and sperm motility rate,regulate sex hormone level and improve the spermatogenic environment,and affect the spermatogenesis process via TGF-β 1/smads signaling pathway.
2.Effect of total flavones of Dracocephalum moldavica L.on high-glucose in-duced oxidative damage to retinal ganglion cells and its mechanism
Liying GU ; Shengfu YANG ; Qiming ZHANG ; Shuxin WANG
Recent Advances in Ophthalmology 2024;44(12):937-942
Objective To investigate the effects of total flavones of Dracocephalum moldavica L.(TFDM)on oxida-tive damage to retinal ganglion cells(RGCs)induced by high glucose(HG)and its mechanism.Methods RGCs of mice were taken as the research subjects.RGCs were inoculated in 24-well plates(with 2.5 × 104 cells in each well)and divided into control group(cultured with medium containing 10%fetal bovine serum for 48 h),HG group(cultured with medium containing 30 mmol·L-1 glucose for 48 h),HG+TFDM-L group(cultured with medium containing 30 mmol·L-1 glucose and 25 mg·L-1 TFDM for 48 h),HG+TFDM-M group(cultured with medium containing 30 mmol·L-1 glucose and 50 mg·L-1 TFDM for 48 h),HG+TFDM-H group(cultured with medium containing 30 mmol·L-1 glucose and 100 mg·L-1 TFDM for 48 h),miR-NC group(transfected with miR-NC and then cultured with medium containing 30 mmol·L-1 glu-cose for 48 h),miR-93-5p group(transfected with miR-93-5p mimics and then cultured with medium containing 30 mmol·L-1 glucose for 48 h),anti-miR-NC group(transfected with anti-miR-NC and then cultured with medium containing 100 mg·L-1 TFDM and 30 mmol·L-1 glucose for 48 h),and anti-miR-93-5p group(transfected with anti-miR-93-5p and then cultured with medium containing 100 mg·L-1 TFDM and 30 mmol·L-1 glucose for 48 h).Levels of RGCs oxidative stress indexes in each group were detected according to the kit instructions.The thiobarbituric acid method was used to measure the level of malondialdehyde(MDA),the colorimetric method was adopted to detect the levels of catalase(CAT)and 8-hydroxydeoxyguanosine(8-OHdG),apoptosis rate was detected by flow cytometry,the messenger ribonucleic acid(mR-NA)expressions were analyzed by real-time quantitative polymerase chain reaction,the targeting regulation of miR-93-5p and E2F transcription factor 1(E2F1)were verified by dual luciferase reporter assay,and the protein expressions were de-tected by Western blot.Statistical analysis was conducted on the data of each group.Results In the HG group,the lev-els of MDA and 8-OHdG,apoptosis rate and Bax protein expression of RGCs were higher than those in the control group(all P<0.05);the CAT level and Bcl-2 protein expression were lower than those in the control group(both P<0.05).In the HG+TFDM-L group,HG+TFDM-M group and HG+TFDM-H group,the levels of MDA and 8-OHdG,apoptosis rate and Bax protein expression of RGCs were lower than those in the HG group(all P<0.05);the CAT level and Bcl-2 protein expression were higher than those in the HG group,and those indexes gradually tended to those in the control group with the increase of TFDM concentrations(all P<0.05).In the HG group,the miR-93-5p expression in RGCs was lower than that in the control group,and the mRNA and protein expressions of E2F1 were higher than those in the control group(all P<0.05).In the HG+TFDM-L group,HG+TFDM-M group and HG+TFDM-H group,the miR-93-5p expression in RGCs was higher than that in the HG group,and the mRNA and protein expressions of E2F1 were lower than those in the HG group(all P<0.05).The protein expression of E2F1 in RGCs of the miR-93-5p group was lower than that in the miR-NC group,and the protein expression of E2F1 in RGCs of the anti-miR-93-5p group was higher than that in the anti-miR-NC group(both P<0.05).In the miR-93-5p group,the miR-93-5p expression was higher than that in the miR-NC group,the levels of MDA and 8-OHdG,apoptosis rate,and protein expressions of Bax and E2F1 were lower than those in the miR-NC group,and the CAT level and Bcl-2 protein expression were higher than those in the miR-NC group(all P<0.05).Con-clusion TFDM can inhibit oxidative stress and cell apoptosis,and then reduce the damage to RGCs induced by HG.The mechanism may involve the regulation of miR-93-5p/E2Fl expression.
3.The safety and protective effect on resting dry mouth of optimized dose optimization in clinical target volume Ⅱa in patients with N 0-N 1 nasopharyngeal carcinoma
Wenxuan HUANG ; Shengfu HUANG ; Siyu ZHANG ; Lanfang ZHANG ; Lijun WANG ; Juying LIU ; Yizhi GE ; Xia HE
Chinese Journal of Radiation Oncology 2024;33(5):397-404
Objective:To analyze the safety of reduced clinical target volume (CTV) irradiation of suspicious positive lymph nodes in IIa region in patients with N 0-N 1 nasopharyngeal carcinoma (NPC) and the protective effect of submandibular gland and long-term resting dry mouth, and to explore the diagnostic value of multimodal imaging for suspicious cervical lymph nodes. Methods:Clinical data of T 0-4N 0-1M 0 stage NPC patients admitted to Jiangsu Cancer Hospital from July 2015 to April 2017 were retrospectively analyzed. Clinical, radiation therapy planning, multimodal imaging and other relevant data were collected. All patients were treated with an optimized regimen of IMRT with a prophylactic radiation dose of 50.4 Gy (named as CTV50) for IIa region. Imaging characteristics and treatment response of suspicious lymph nodes were monitored by MRI, MRI-DWI, PET-CT and repeated enhanced positioning CT, etc. The dosimetry of the submandibular gland between optimized and standard dose plans (CTV50 vs. CTV60) was compared by paired t-test. The long-term dry mouth degree of the patients was evaluated using advanced radiation injury from Radiation Therapy Oncology Group (RTOG), Jiangsu Cancer Hospital Multi-dimensional Dry Mouth Evaluation Scale and summated xerostomia inventory (SXI). The difference of dry mouth degree was analyzed by rank-sum test. Results:A total of 106 patients were included in this study, including 149 cervical lymph node negative sides, 73 sides of which had ≤3 recognizable lymph nodes, and 76 of which were>3 in Ⅱa region. Among patients with N 1 stage, 63 patients underwent contralateral single neck area optimization, and 43 patients (N 0 stage and N 1 stage patients with retropharyngeal lymph node metastasis) underwent double-neck area optimization. A total of 109 suspicious lymph nodes with a short diameter of >5 mm were found on the largest cross section, of which 105 had clear portal structure. The ratio of long to short diameter was ≥1.5 in 93 cases, and the maximum standardized uptake value (SUV max) in PET-CT was ≥2.5 in 76 cases. No lymph node recurrence was found in the CTV optimized area. There was no significant difference in the average dose of GTV in tumor target area after optimization ( P>0.05), and the D mean and V 39 Gy in submandibular gland were significantly lower than those in unoptimized plan (both P<0.01). There was no significant difference in long-term dry mouth and resting dry mouth between patients with unilateral and bilateral optimization of submandibular gland (both P>0.05). Conclusions:The optimal program of CTV50 reduction irradiation in Ⅱa area of N 0-N 1 NPC patients is safe and effective. The submandibular gland has obvious dosimetric advantages, and patients have a good subjective response to resting dry mouth. The multimodal imaging tools such as enhanced CT, MRI-DWI and PET-CT should be performed to deliver individual evaluation and treatment for suspicious lymph nodes.
4.Treatment strategy and prognostic analysis of nasopharyngeal necrosis after first radical radiotherapy for nasopharyngeal carcinoma
Dan ZONG ; Wenxuan HUANG ; Yesong GUO ; Jing WEN ; Lijun WANG ; Lanfang ZHANG ; Lirong WU ; Cheng CHEN ; Shengfu HUANG ; Xia HE ; Zhenzhang CHEN
Chinese Journal of Radiation Oncology 2024;33(9):797-803
Objective:To investigate the treatment strategy and prognostic factors of nasopharyngeal necrosis after the first radical radiotherapy for nasopharyngeal carcinoma.Methods:Clinical data of 1020 patients with nasopharyngeal carcinoma undergoing radical intensity-modulated radiotherapy in Jiangsu Cancer Hospital from January 2013 to January 2022 were retrospectively analyzed. Nasopharyngeal necrosis was confirmed by nasopharyngeal MRI, electronic nasopharyngoscopy and biopsy. Patients with nasopharyngeal necrosis were treated with electronic nasopharyngoscope irrigation debridement, combined with systemic anti-infection and nutritional support therapy. Kaplan-Meier method was used to calculate the survival, and Cox regression analysis was used to analyze the relationship between clinical factors and patients' survival.Results:Nasopharyngeal necrosis occurred in 20 cases of 1020 nasopharyngeal carcinoma patients after the first radical intensity-modulated radiotherapy, with an incidence rate of 1.96%. Odd smell and headache were common in nasopharyngeal necrosis patients. All patients had locally advanced nasopharyngeal carcinoma at initial treatment, including 2 (10%) cases of T 3 stage and 18 (90%) cases of T 4 stage. Nasopharyngeal necrosis occurred in the primary nasopharyngeal lesions. According to the stages of nasopharyngeal necrosis, there were 6 (30%) cases of stage I, 14 (70%) cases of stage II and no stage III. The occurrence time of nasopharyngeal necrosis was from 2 to 24 months after radiotherapy, and the median time was 5 months. All 16 cases of nasopharyngeal necrosis were cured clinically after debridement and irrigation under nasopharyngoscope, systemic anti-infection and symptomatic support treatment. Among them, 9 cases had no necrotic cavity and complete healing and 7 cases had residual necrotic cavity. Four patients died of massive nasopharyngeal hemorrhage or due to the inability to nasopharyngeal irrigation. The 5-year survival rates were 37.5% and 85.7% in patients with and without internal carotid artery involvement ( P=0.008), and 25.0% and 77.8% in patients with and without diabetes mellitus ( P=0.016). Univariate Cox regression analysis showed that necrotic lesions involving internal carotid artery ( HR=5.80, 95% CI=1.14-29.38, P=0.034) and diabetes mellitus ( HR=10.24, 95% CI=1.19-88.04, P=0.034) were the influencing factors of overall survival. Conclusions:Nasopharyngoscope irrigation debridement combined with anti-inflammation and nutritional support treatment are effective interventions for nasopharyngeal necrosis after the first radical intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma. The necrosis involving the internal carotid artery and diabetes mellitus are important factors affecting the survival of patients. Vascular invasion caused by vascular rupture is the main cause of death.
5.The feasibility of individualized primary CTV for lateralized nasopharyngeal carcinoma
Siyu ZHANG ; Wenxuan HUANG ; Lijun WANG ; Juying LIU ; Lijun ZHAO ; Lirong WU ; Dejun WANG ; Wenjing XU ; Yesong GUO ; Pengwei YAN ; Lanfang ZHANG ; Zhenyu ZHAI ; Shengfu HUANG ; Xia HE
Chinese Journal of Radiation Oncology 2023;32(8):675-682
Objective:To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).Methods:Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results:The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side ( P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion:Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.
6.The strategy and feasibility of dose optimization in clinical target volume Ⅱb in patients with N 0-N 1 nasopharyngeal carcinoma
Wenxuan HUANG ; Dan ZONG ; Bin ZHANG ; Lijun WANG ; Lanfan ZHANG ; Chengxian MA ; Li YIN ; Shengfu HUANG ; Xia HE
Chinese Journal of Radiation Oncology 2022;31(9):778-784
Objective:To determine the safety of prophylactic irradiation dose CTV 60Gy optimized to CTV 50Gy for II b region in patients with stage N 0-N 1 nasopharyngeal carcinoma (NPC) and the dose advantage and clinical value for parotid gland protection, and to understand the diagnostic value of PET-CT and diffusion-weighted imaging (DWI) for suspicious positive lymph nodes in the neck (5 mm≤maximum short diameter<10 mm). Methods:Clinical data of 157 patients with primary non-metastatic NPC (N 0-N 1) admitted to our hospital from June 2015 to March 2017 were retrospectively analyzed. 104 patients underwent II b clinical target volume optimization guided by multimodal imaging system. Survival analysis was performed by Kaplan - Meier method. Univariate/multivariate regression analysis was performed to analyze the pattern of cervical lymph node recurrence. Paired t-test was used to compare the differences in target volume and parotid gland dose parameters before and after dose optimization. Results:Sixty patients underwent single-neck optimization in stage N 1, 25 patients received double-neck optimization (only those with retropharyngeal lymph node metastasis), and 19 patients underwent double-neck optimization in stage N 0. Three patients had cervical regional recurrence, all in-field. The 5-year overall survival rate was 93.3%. The lymph node recurrence-free survival rate, local recurrence-free survival rate, distant metastasis-free survival rate and disease-free survival rate were 97.1%, 91.3%, 88.5% and 80.8%, respectively. Cervical lymph node recurrence was associated with local recurrence in the nasopharynx, regardless of retropharyngeal lymph node status. Fourteen patients had suspicious positive cervical lymph nodes in II b region, with a mean maximum short diameter of 7.1 (5~9) mm on the largest cross-sectional plane, and 11 of them were positive on PET-CT, with a mean SUV max of 2.96 (2.5~3.3). There was no significant difference in GTV after optimization ( P>0.05). D mean, D max, D 50% and V 26Gy of parotid gland were significantly lower than those of conventional plan (all P<0.01). Conclusions:It is safe to optimize CTV 60Gy to CTV 50Gy in II b region in patients with N 0-N 1 NPC, and the exposure dose to normal tissues around the parotid gland and neck is significantly reduced. For small lymph nodes that do not meet the diagnostic criteria, it needs to be individualized in combination with multimodality imaging systems, such as PET-CT and DWI.
7. The risk factors of parotid lymph node metastasis of nasopharyngeal carcinoma and the feasibility of local intensity-modulated radiotherapy for high-risk patients
Yongqin ZHANG ; Yun ZUO ; Jing WEN ; Lijun WANG ; Lanfang ZHANG ; Shengfu HUANG
Chinese Journal of Radiation Oncology 2019;28(9):652-656
Objective:
To investigate the high-risk factors for parotid lymph node (PLN) metastasis from nasopharyngeal carcinoma (NPC) and evaluate the feasibility of local intensity-modulated radiotherapy (IMRT) in patients with high-risk NPC.
Methods:
Clinical data of 440 NPC patients admitted to Department of Radiotherapy of Jiangsu Cancer Hospital from May, 2011 to March, 2017 were collected. The imaging features, treatment strategies and clinical prognosis of PLN metastasis were retrospectively analyzed. The whole group adopts the technique of intensity modulated radiotherapy. Total parotid or partial parotid irradiation, selective PLN irradiation, X-Ray and/or electronic line supplementation, dose 45-60 Gy. The
8.Clinical value of magnetic resonance diffusion-weighted imaging in early diagnosis and treatment of cervical lymph node recurrence after radiotherapy of nasopharyngeal carcinoma
Dayong GU ; Shengfu HUANG ; Dan ZONG ; Cheng CHEN ; Jing WEN ; Lanfang ZHANG
Chinese Journal of Radiation Oncology 2019;28(8):571-574
Objective To explore the clinical value of magnetic resonance diffusion-weighted imaging ( MR-DWI ) in the early diagnosis of cervical lymph node recurrence after radiotherapy of nasopharyngeal carcinoma, aiming to provide reference for targeted diagnosis and treatment of these patients. Methods The MR-DWI features of 17 patients with recurrent cervical lymph nodes after radiotherapy from 2005 to 2016 were retrospectively analyzed. The results of diagnosis and treatment after lymph node recurrence were summarized. Results The recurrent lymph nodes of 17 patients showed a high signal or mixed signal on MR-DWI images. The sensitivity of MR-DWI and T2WI fat suppression sequence was 100% and 60%. Positron emission tomography-computed tomography ( PET-CT) or biopsy was performed to validate the diagnosis in patients with highly suspected single cervical recurrence. Besides, surgical treatment yielded better clinical prognosis. Conclusions MR-DWI is highly sensitive to recurrent cervical lymph nodes of nasopharyngeal carcinoma after radiotherapy, especially for the small lymph nodes of 5-10 mm in diameter, which are easily ignored. PET-CT examination should be performed, the nature of the lymph nodes should be confirmed by multi-modality imaging diagnosis, and timely operation has important clinical significance in improving the therapeutic effect and quality of life for patients with cervical lymphnode recurrence.
9.Investigation and Analysis of the Influencing Factors of Informed Consent of Subjects in Drug Clinical Trial
Yue ZHANG ; Xiaoyun CHEN ; Shengfu YOU
Chinese Medical Ethics 2018;31(2):213-219
Taking a class A tertiary hospital in Shanghai as center, this paper understood the awareness of the subjects of drug clinical trials on their participation in the research and their own rights as subjects after the end of research (6~18 months) by questionnaire survey completed by telephone interview, analyzed the problems existing in the process of informed consent, compared with the foreign status, and summed up a variety of feasible ways of subject' s own right to be informed, to put forward feasible suggestions for the development and improvement of medical scientific research management and the ethical work in China.
10.Imaging diagnosis of the medial group of retropharyngeal lymph nodes and the exploration of the optimization of target volume for protecting the swallowing structure in nasopharyngeal carcinoma
Dan ZONG ; Lanfang ZHANG ; Cheng CHEN ; Dayong GU ; Xia HE ; Shengfu HUANG
Chinese Journal of Radiation Oncology 2018;27(12):1035-1040
Objective To clarify the diagnostic value of diffusion-weighed imaging ( DWI) in the medial group of retropharyngeal lymph nodes in nasopharyngeal carcinoma, understand the clinical characteristics of retropharyngeal lymph nodes and explore the feasibility of optimizing the target volume of CT V60. Methods Clinical data of 437 patients with clinical stage Ⅰ-IVa nasopharyngeal carcinoma admitted to Jiangsu Cancer Hospital from 2011 to 2017 were retrospectively analyzed. All patients underwent magnetic resonance imaging (MRI),DWI (1 000 s/mm2) and enhanced CT scans to analyze the clinical characteristics of retropharyngeal lymph nodes and investigate the dosimetric advantage and safety of CT V60 lower margin on the upper margin of C2. Results The medial lymph nodes with a transverse diameter of 2. 0-19. 0 mm were detected 13 of 437 patients,and 53. 8% of the lymph nodes were measured 2-5 mm in transverse diameter. The medial lymph nodes were distributed between the superior margin of C1and 1/3 of C3.Its occurrence was related to N stage,double cervical lymph node metastases,especially the transverse diameter of cervical lymph node> 3 cm.The sensitivity of DWI,T2and enhanced CT were 100%,61. 5% and 23. 1%.After the special cases were excluded,the lower margin of CT V60on the superior margin of C2was separated. The radiation dose and volume of the swallowing structures were significantly decreased. The 5-year survival rate was 80% without recurrence in the optimized region. Conclusions The incidence of the medial group of retropharyngeal lymph nodes is low with a diameter of less than 5 mm. DWI possesses advantages in displaying the medial group of retropharyngeal lymph nodes. Isolating the lower margin of CT V60from the superior margin of C2is safe and feasible and has dosimetric advantages for protecting swallowing structure.

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