1.PROTAC-loaded nanocapsules degrading BRD4 for radio-chemotherapy sensitization in glioblastoma.
Yun GUO ; Mingzhu FANG ; Shilin ZHANG ; Zheng ZHOU ; Zonghua TIAN ; Haoyu YOU ; Yun CHEN ; Jingyi ZHOU ; Xiaobao YANG ; Yunke BI ; Chen JIANG ; Tao SUN
Acta Pharmaceutica Sinica B 2025;15(10):5050-5070
Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.
2.Application of progressive case teaching method based on core competency in standardized nursing training
Xiaoying CHEN ; Fei CHEN ; Jinyu QIAN ; Yifei ZHANG ; Zonghua WANG ; Lei LIU ; Jishu XIAN
Chinese Journal of Medical Education Research 2023;22(7):1088-1093
Objective:To explore the application effect of progressive case teaching method based on core competency in standardized nursing training.Methods:A total of 63 nursing students rotated in department of neurosurgery from June 2020 to June 2022 were selected as the research objects and randomized into experimental group ( n=31) and control group ( n=32). The experimental group adopted the progressive case teaching method based on core competency, and the control group adopted the conventional teaching mode. The data was analyzed using SPSS 26.0 to conduct t-test or non-parametric test based on the data normality for comparing the theory results, objective structure clinical examination (OSCE) scores, core competency, self-directed learning ability scores, teaching satisfaction and nursing satisfaction of patients in two wards between the two groups. Results:The theoretical results ( t=4.74, P<0.001) and OSCE scores ( t=3.81, P<0.001) of the experimental group were better than those of the control group. The scores of core competency and autonomous learning ability ( t=4.32, P<0.001) of the experimental group were better than those of the control group. The teaching satisfaction score ( t=2.21, P=0.044) and patient satisfaction score ( t=2.92, P=0.011) of the observation group were better than those of the control group. Conclusion:The progressive case teaching method based on core competency can improve the post competency of nurses, and also improve the teaching satisfaction rate and patient satisfaction rate, which is worthy of being carried out in the subsequent teaching activities.
3.Summary of best evidence for pulse contour cardiac output monitoring in severe burn patients
Zonghua WANG ; Jiangshan FAN ; Yuanyuan MI ; Ling CHEN ; Langlang XIE ; Ning LI
Chinese Journal of Burns 2023;39(6):573-580
Objective:To summarize the best evidence for pulse contour cardiac output (PiCCO) monitoring in severe burn patients.Methods:A bibliometric approach was used. Foreign language databases including UpToDate, BMJ Best Practice, Joanna Briggs Institute Evidence-Based Practice Database, Cochrane Library, PubMed, Web of Science, Embase, Medline, and Guideline International Network, as well as Chinese databases such as China National Knowledge Infrastructure, Wanfang Database, and VIP Database were systematically retrieved to obtain all the publicly published evidence on PiCCO monitoring in severe burn patients in each database from the establishment of each database to May 2022, including guidelines, expert consensus, evidence summary, systematic review, and original research. The literature was screened and evaluated for the quality, from which the evidences were extracted, evaluated, and classified to summarize the best evidences.Results:Three guidelines, two expert consensuses, one evidence summary (with two systematic reviews being traced), two systematic reviews, three randomized controlled trials, one cohort study, and one case-control study were retrieved and included, with good quality of literature. Totally 37 pieces of best evidences about PiCCO monitoring in severe burn patients were summarized from the aspects of pre-operation evaluation, pipe placement and operation, monitoring system establishment, pipeline maintenance, and supervision and education.Conclusions:Totally 37 pieces of best evidences about PiCCO monitoring in severe burn patients are summarized from 5 aspects, providing a basis for the clinical implementation of scientific and standardized PiCCO monitoring and nursing management.
4.Interpretation of the Guideline for Pharmaceutical Excipients of Animal Origin
Chunmeng SUN ; Lei CHEN ; Yanan LI ; Zonghua SONG ; Zhaopeng YANG ; Jiasheng TU
Journal of China Pharmaceutical University 2022;53(3):376-382
Pharmaceutical excipients of animal origin, an important part in pharmaceutical excipients, are widely used in pharmaceutical preparations.However, compared with the pharmaceutical excipients of other origins, pharmaceutical excipients of animal origin have more special requirements in many aspects, such as raw materials, production, quality control, storage, supervision, etc.Chinese Pharmacopoeia 2020 first included the Guideline for Pharmaceutical Excipients of Animal Origin, which introduces the basic ideas and technical requirements for the life cycle quality control of pharmaceutical excipients of animal origin based on the risk management concept.This article illustrates the specificity of the pharmaceutical excipients of animal origin, and interprets the main contents of this guideline in conjunction with relevant domestic and foreign regulations and technical documents, thereby providing comprehensive reference for the implementation of the guideline.
5. Effects of neonatal intensive care unit-centered regional transport network on treatment of retinopathy of prematurity
Qiuping LI ; Zonghua WANG ; Xiumei YANG ; Haihua CHEN ; Hongyi TANG ; Zhichun FENG
Chinese Journal of Perinatal Medicine 2019;22(9):627-632
Objective:
To investigate the effects of neonatal intensive care unit (NICU)-centered regional neonatal transport network (NTN) on the treatment of retinopathy of prematurity (ROP).
Methods:
A retrospective analysis was conducted to analyze the transfer, treatment and outcomes of 406 preterm infants with ROP who were transferred to the Bayi Children's Hospital Affiliated to the Seventh Medical Center of PLA General Hospital via the NTN from July 2008 to December 2014. Independent sample
6. Effects of anteriolateral thigh perforator flap and fascia lata transplantation in combination with computed tomography angiography on repair of electrical burn wounds of head with skull exposure and necrosis
Xiaoqing LI ; Xin WANG ; Yalong HAN ; Gang JI ; Zonghua CHEN ; Jia ZHANG ; Jianping ZHU ; Jianxing DUAN ; Yongjing HE ; Xiaomin YANG ; Wenjun LIU
Chinese Journal of Burns 2018;34(5):283-287
Objective:
To explore the effects of anteriolateral thigh perforator flap and fascia lata transplantation in combination with computed tomography angiography (CTA) on repair of electrical burn wounds of head with skull exposure and necrosis.
Methods:
Seven patients with head electrical burns accompanied by skull exposure and necrosis were admitted to our burn center from March 2016 to December 2017. Head CTA was performed before the operation. The diameters of the facial artery and vein or the superficial temporal artery and vein were measured, and their locations were marked on the body surface. Preoperative CTA for flap donor sites in lower extremities were also performed to track the descending branch of the lateral circumflex femoral artery with the similar diameter as the recipient vessels on the head, and their locations were marked on the body surface. Routine wound debridement and skull drilling were performed successively. The size of the wounds after debridement ranged from 12 cm×8 cm to 20 cm×12 cm, and the areas of skull exposure ranged from 8 cm×6 cm to 15 cm×10 cm. Anteriolateral thigh perforator flaps with areas from 13 cm×9 cm to 21 cm×13 cm containing 5-10 cm long vascular pedicles were designed and dissected accordingly. The fascia lata under the flap with area from 5 cm×2 cm to 10 cm×3 cm was dissected according to the length of vascular pedicle. The fascia lata was transplanted to cover the exposed skull, and the anteriolateral thigh perforator flap was transplanted afterwards. The descending branch of the lateral circumflex femoral artery and its accompanying vein of the flap were anastomosed with superficial temporal artery and vein or facial artery and vein before the suture of flap. The flap donor sites were covered by intermediate split-thickness skin graft collected from contralateral thigh or abdomen.
Results:
The descending branch of the lateral circumflex femoral artery and its accompanying vein were anastomosed with superficial temporal artery and vein in six patients, while those with facial artery and vein in one patient. All the flaps survived after the operation, and no vascular crisis was observed. Wound healing was satisfactory. One patient was lost to follow up. Six patients were followed up for 6 to 10 months. The patients were bald in the head operation area with acceptable appearance. No psychiatric symptom such as headache or epileptic seizure was reported. The flap donor sites were normal in appearance. The muscle strength of the lower extremities all reached grade V. The sensation and movement of the lower extremities were normal.
Conclusions
Anterolateral thigh perforator flap with fascia lata transplantation can effectively repair electrical burn wounds of head with skull exposure and necrosis. The fascia lata can be used to protect the vascular pedicle of flaps, which is beneficial to the survival of the flap. Preoperative head and lower extremities CTA can provide reference for intraoperative vascular exploration in donor site and recipient area, so as to shorten operation time.
7.Imaging features and pathological analysis of calvarial cavernous hemangioma
Guangfu DI ; Yangyang HU ; Xiaochun JIANG ; Zonghua XU ; Shanshui XU ; Cegang LIU ; Sansong CHEN ; Yi DAI
Chinese Journal of Nervous and Mental Diseases 2017;43(4):225-228
Objective To investigate the imaging features of the calvarial cavernous hemangioma and the surgical efficacy to improve diagnosis and treatment of the calvarial cavernous hemangioma.Methods The clinical information,imaging materials and surgical efficacy from ten cases of calvarial cavernous hemangioma confirmed by pathology and the related literature was reviewed.Results The lesion was located in frontal bone in eight cases,in parietal bone in one case and in occipital bone in one case.The lesions were round-shape hypodensity with clear margin in X-ray.The lesions were hyperdensity or slightly hyperdensity on CT scan,and were osteolytic lesions with a characteristic honeycomb or starburst pattern on bone window.The MRI features were complicated and variable.The lesions were heterogenous and unevenly enhanced signal intensity.Nine patients underwent radical resections and reconstructed immediately by titanium mesh.The patient with tumor in occipital bone underwent radical resection only.Macroscopically,the pathologic bone was a huge purple-red blush mass protruding from the skull surface.Histological examination revealed the diploe with large,thin-walled,dilated blood-filled spaces lined by flattened endothelial cells without evidence of malignancy.No recurrence was noted in any case during a follow-up period from 3 to 24 months.All the patients survived well without recurrence.Conclusions The imaging features of calvarial cavernous hemangioma have a high value in the diagnosis and may provide guidance for the treatment.The radical resection and immediate reconstruction treatment for calvarial cavernous hemangioma is satisfied.
8.Feasibility of different xenogeneic (porcine) acellular dermal matrices in the repair of deep burn wounds:a 12-month follow-up
Ming ZENG ; Dinan WEI ; Yan ZHI ; Hong WANG ; Zonghua CHEN
Chinese Journal of Tissue Engineering Research 2016;20(11):1551-1557
BACKGROUND:Skin grafting is crucial for patients with deep burns, but limited source of autologous skin grafts is an existing difficulty.
OBJECTIVE:To investigate the effect of xenogeneic (porcine) acelular dermal matrix in the treatment of deep burn wounds and the feasibility of its application.
METHODS:Forty-one patients with deep burn were divided into two groups according to the intention of the patients, 21 cases in control group and 20 cases in observational group, folowed by autologous split-thickness skin grafting alone or combined with different (porcine) acelular dermal matrix, respectively. After 12 months of folow-up, the graft success rate at postoperative 1, 2, 3, 4 weeks and skin graft contraction rate and wound repair at postoperative 3, 6, 9, 12 months were observed and compared between two groups. Moreover, levels of inflammatory factors were detected and compared between two groups at postoperative 1, 2, 3 months.
RESULTS AND CONCLUSION: The skin graft success rates showed no difference between two groups at postoperative 1, 2, 3, 4 weeks (P > 0.05). The skin graft contraction rates also showed no difference between two groups at postoperative 3, 6, 9, 12 months (P > 0.05). After 12 months of folow-up, no serious scar hyperplasia, but soft texture appeared in the control group. In the observational group, three cases presented with local pigmentation at the early stage, but it gradualy subsided with time; no obvious scar, but only smal, point-like scar, was visible, and the repaired wound exhibited soft touch. No adverse events and death occurred in both two groups. Experimental results show that the treatment of deep burns with autologous split-thickness skin grafting combined with xenogeneic (porcine) acelular dermal matrix is safe and effective, which can improve the quality of wound healing.
9.Coping ways and influence factors of the migrant workers of the generation after 90s in Shenzhen
Suwen CHEN ; He WU ; Shike LUO ; Xiuling HUANG ; Jing GAN ; Zonghua XIANG ; Jiarong LIU
Chinese Journal of Modern Nursing 2014;20(21):2617-2620
Objective To analyze the coping ways and influence factors of the migrant workers of the generation after 90s in Shenzhen.Methods By cluster sampling, 614 migrant workers of the generation after 90 s were surveyed with demographic data and the Simplified Coping Style questionnaire ( SCSQ ) .Results Among 614 participants the score of coping ways was (1.85 ±0.44), higher than the norm, and the negative coping score was (1.14 ±0.52), lower than the norm.The differences were statistical significant (t =-3.87,-21.34, respectively;P<0.01).There were 487 participants (79.3%) in the normal state of positive coping ways,and 376 participants (61.2%) in the normal state of negative coping ways .The education level and gender were the influence factors of coping ways , within which the education level had a significant positive effect on the coping ways (F=4.015, P=0.019), and the influence factors had a significant negative effect on the coping ways (t=3.230, P=0.001).Conclusions Most of the employee of the generation after 90 s are at a normal state of coping , and have preferable coping ways .The education level and gender are the factors that influence the ways of the behavior and reaction .The inferiority, timidity, atresia and loneliness were found among these employee during the investigation .
10.Diagnosis and treatment of metanephric adenoma
Gang LI ; Zonghua GUO ; Changyi QUAN ; Shumin ZHANG ; Jing CHEN ; Juan WANG ; Yi WANG ; Yuanjie NIU
Chinese Journal of Urology 2012;33(1):47-50
Objective To explore the clinical and histopathological features of metanephric adenoma (MA). MethodsClinical and pathological data of 10 cases of MA were analyzed retrospectively.There were 4 males and 6 females,aged from 33 to 65 years,with an average of 45 years.2 patients had flank pain,4 patients had gross hematuria,and 4 patients were found by physical examination.The average diameter of tumor was 4.5 cm (2.5 - 8.0 cm).All patients were diagnosed as renal tumor by CT scan.9 patients underwent radical nephrectomy and 1 patient underwent partial nephrectomy. Results Pathological examination found that the tumors are composed of densely packed small uniform cells with regular nuclei that formed a tubular or adenoid pattern.Mitotic figures were absent or rare.4 patients were diagnosed as MA,2 cases were diagnosed as low-grade malignant MA,and 4 cases were diagnosed as MA with malignant component (2 cases of adenocarcinoma,1 case of chromophobe cell carcinoma,and 1 case of well differentiated papillary adenocarcinoma),7 cases were followed up for 22 months ( 10 to 34 months) without recurrence or metastasis. Conclusions MA is very rare benign renal tumor originating from epithelium,and a few are malignant,and some may contain malignant ingredients.Nephron-sparing surgery and radical nephrectomy are eligible for the treatment of MA.Considering the uncertainty of the biological behavior and cellular origin of MA,a long-term follow-up is necessary.

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