1.Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy.
Hui YU ; Aliya TIEMUER ; Xufeng YAO ; Mingyuan ZUO ; Hai-Yan WANG ; Yi LIU ; Xiaoyuan CHEN
Acta Pharmaceutica Sinica B 2024;14(1):378-391
Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment. However, there are limitations, including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision, associated with gas therapy. In this study, we developed a series of photoactivatable nitric oxide (NO) donors NRh-R-NO (R = Me, Et, Bn, iPr, and Ph) based on an N-nitrosated upconversion luminescent rhodamine scaffold. Under the irradiation of 808 nm light, only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence (FUCL) signal at 740 nm, ascribed to lower N-N bond dissociation energy. We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy, including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation, the superoxide anion O2⋅- produced by the photodynamic therapy (PDT) effect of NRh-Ph, and highly toxic peroxynitrite anion (ONOO‒) generated from the co-existence of NO and O2⋅-. After mild nano-modification, the nanogenerator (NRh-Ph-NO NPs) empowered with superior biocompatibility could target mitochondria. Under an 808 nm laser irradiation, NRh-Ph-NO NPs could induce NO/ROS to generate RNS, causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation, which further induced tumor immunogenic cell death (ICD). In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy, demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging. Collectively, this versatile strategy defines the targeted RNS-mediated cancer therapy.
2.Study on the application value of fecal SDC2 gene methylation detection in colorectal cancer screening of urban residents in Zengcheng District in Guangzhou City
Yan HE ; Fangfang XU ; Haijun ZUO ; Wei CHEN ; Zhibin LIU ; Zebang LIU ; Xuezhen CHEN ; Qingshen HUI ; Gengwen ZOU ; Zhenbin CAI ; Yang LIU ; Haoshun TAN ; Hongfeng ZHOU ; Jianping WANG
Chinese Journal of Preventive Medicine 2024;58(7):1020-1028
Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.
3.Study on the application value of fecal SDC2 gene methylation detection in colorectal cancer screening of urban residents in Zengcheng District in Guangzhou City
Yan HE ; Fangfang XU ; Haijun ZUO ; Wei CHEN ; Zhibin LIU ; Zebang LIU ; Xuezhen CHEN ; Qingshen HUI ; Gengwen ZOU ; Zhenbin CAI ; Yang LIU ; Haoshun TAN ; Hongfeng ZHOU ; Jianping WANG
Chinese Journal of Preventive Medicine 2024;58(7):1020-1028
Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.
4.New progress and challenges in the diagnosis and treatment of cosmetic allergy-related adverse reactions.
Chong ZHANG ; Shao Min ZHONG ; Yan WU ; Jia Hui ZHAO ; Zuo Tao ZHAO ; Yan TIAN ; Hang LI
Chinese Journal of Preventive Medicine 2023;57(4):591-596
In China, the current standard for cosmetic adverse reactions related skin disease (GB/T 17149.1-1997) was jointly issued by the Ministry of Health and the State Bureau of Technical Supervision in 1997, cosmetic-allergic adverse reactions include allergic contact dermatitis and photo-allergic contact dermatitis according to this standard. The increasing use and changes in cosmetic ingredients or formula lead to a significant increase for the incidence of adverse reactions as the cosmetics industry is developing rapidly in the last 20 years. In the meantime, the clinical manifestations have become more diverse. In recent years, there have been many reports on the special manifestations for cosmetic allergy and allergen test, which provide a reference for the subsequent improvement of the diagnosis and prevention.
Humans
;
Patch Tests/adverse effects*
;
Dermatitis, Allergic Contact/therapy*
;
Cosmetics/adverse effects*
;
China
;
Incidence
;
Allergens/adverse effects*
5.The timing of pericardial drainage catheter removal and restart of the anticoagulation in patients suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran: Experiences from 20 cases.
Xin ZHAO ; Wen Li DAI ; Xin SU ; Jia Hui WU ; Chang Qi JIA ; Li FENG ; Man NING ; Yan Fei RUAN ; Song ZUO ; Rong HU ; Xin DU ; Jian Zeng DONG ; Chang Sheng MA
Chinese Journal of Cardiology 2023;51(1):45-50
Objective: To investigate the timing of pericardial drainage catheter removal and restart of the anticoagulation in patients with atrial fibrillation (AF) suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran. Methods: A total of 20 patients with pericardial tamponade, who underwent AF catheter ablation with uninterrupted dabigatran in Beijing Anzhen Hospital from January 2019 to August 2021, were included in this retrospective analysis. The clinical characteristics of enrolled patients, information of catheter ablation procedures, pericardial tamponade management, perioperative complications, the timing of pericardial drainage catheter removal and restart of anticoagulation were analyzed. Results: All patients underwent pericardiocentesis and pericardial effusion drainage was successful in all patients. The average drainage volume was (427.8±527.4) ml. Seven cases were treated with idarucizumab, of which 1 patient received surgical repair. The average timing of pericardial drainage catheter removal and restart of anticoagulation in 19 patients without surgical repair was (1.4±0.7) and (0.8±0.4) days, respectively. No new bleeding, embolism and death were reported during hospitalization and within 30 days following hospital discharge. Time of removal of pericardial drainage catheter, restart of anticoagulation and hospital stay were similar between patients treated with idarucizumab or not. Conclusion: It is safe and reasonable to remove pericardial drainage catheter and restart anticoagulation as soon as possible during catheter ablation of atrial fibrillation with uninterrupted dabigatran independent of the idarucizumab use or not in case of confirmed hemostasis.
Humans
;
Atrial Fibrillation/drug therapy*
;
Dabigatran/therapeutic use*
;
Cardiac Tamponade/complications*
;
Anticoagulants/therapeutic use*
;
Retrospective Studies
;
Treatment Outcome
;
Drainage/adverse effects*
;
Catheter Ablation
;
Catheters/adverse effects*
6.Clincal practice of pelvic exenteration for late complications of pelvic radiation injury.
Teng Hui MA ; Yan Jiong HE ; Zuo Lin ZHOU
Chinese Journal of Gastrointestinal Surgery 2023;26(3):235-240
Pelvic radiation injury can potentially involve multiple pelvic organs, and due to its progressive and irreversible nature, its late stage can be complicated by fistulas, perforations, obstructions and other complications involved multiple pelvic organs, which seriously affect the long-term survival and the quality of life of patients. As a multidisciplinary surgical approach, pelvic exenteration has potential application in the treatment of late complications of pelvic radiation injury by completely removing the irradiated lesion, relieving symptoms and avoiding recurrence of symptoms. In clinical practice, we should advocate the concept of "pelvic radiation injury", emphasize multidisciplinary collaboration, fully evaluate the overall status of patients, primary tumor and pelvic radiation injury. We should follow the principles of "damage-control" and "extended resection", and follow the principle of enhanced recovery after surgery to achieve the goal of ensuring the surgical safety, relieving patients' symptoms and improving patients' quality of life and long-term survival.
Humans
;
Pelvic Exenteration/adverse effects*
;
Postoperative Complications
;
Quality of Life
;
Radiation Injuries/surgery*
;
Neoplasm Recurrence, Local/surgery*
;
Retrospective Studies
7.Clinical Effect of Unilateral Biportal Endoscopic Lumbar Interbody Fusion and Minimally Invasive Transforaminal Lumbar Interbody Fusion on Single-segment Lumbar Stenosis with Instability.
Chao JIANG ; Yong-Hui HUANG ; Hua ZUO ; Yan SUN ; Ji-Fu SUN
Acta Academiae Medicinae Sinicae 2022;44(4):563-569
Objective To compare the early clinical effects of unilateral biportal endoscopic lumbar interbody fusion (ULIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF)on single-segment lumbar stenosis with instability. Methods The patients who had single-segment lumbar spinal stenosis with instability and were treated in our hospital from August 2020 to May 2021 were selected.According to the operation methods,they were classified into ULIF group and MIS-TLIF group.The operation duration,hospital stay after operation,perioperative blood loss (drainage volume 48 h after operation,total blood loss),creatine kinase,inflammatory cytokines (C-reactive protein,interleukin-6),D-dimer,and the incidence of lower-extremity venous thrombosis were compared between the two groups.The visual analogue scale and Oswestry disability index were used to evaluate the functional recovery of the two groups in 1 week,1 month,and 3 months after operation. Results The ULIF group had longer operation duration (P<0.001) and shorter hospital stay after operation (P=0.022)than the MIS-TLIF group.The drainage volume 48 h after operation and total blood loss in ULIF group were lower than those in MIS-TLIF group (all P<0.001).The levels of creatine kinase (all P<0.001),C-reactive protein (P<0.001,P=0.002),and interleukin-6 (P=0.003,P<0.001) in ULIF group were lower than those in MIS-TLIF group on the 1st and 3rd day after operation.However,the D-dimer in ULIF group was insignificantly different from that in MIS-TLIF group on the 1st and 3rd day after operation (P=0.117,P=0.683).Lower-extremity venous thrombosis occurred in neither group.The score of visual analogue scale showed no significant difference between the two groups 1 week,1 month,and 3 months after operation (P=0.447,P=0.578,P=0.538),so did the Oswestry disability index (P=0.832,P=0.797,P=0.619). Conclusion ULIF shows similar clinical effect on single-segment lumbar stenosis with instability to MIS-TLIF,which features less bleeding,mild inflammation,mild muscle injury,but long operation duration.
C-Reactive Protein
;
Constriction, Pathologic
;
Creatine Kinase
;
Humans
;
Interleukin-6
;
Lumbar Vertebrae/surgery*
;
Minimally Invasive Surgical Procedures/methods*
;
Spinal Fusion
;
Venous Thrombosis
8. Endothelial Progenitor Cells Derived from mESCs Were Directed to Differentiate into Vascular Endothelial Cells and Promote Wound Healing
Feng-Jiao CHEN ; Zhao-Yan ZUO ; Jia-Hui LV ; Ying YANG ; Liu YANG ; Jie DING ; Qian PENG ; Ying LU
Chinese Journal of Biochemistry and Molecular Biology 2022;38(3):320-332
Ischemic dysfunction is an important global health problem. Vascular endothelial cells(VECs) play a key role in angiogenesis, and insufficient vascular remodeling may lead to chronic nonhealing wounds. Therefore, effective VEC generation strategies of exploration help improve angiogenesisin damaged tissues. Embryonic stem cells (ESCs) are widely used in the study of tissueendothelialization, and endothelial progenitor cells (EPCs) are indispensable parts of the development ofVECs. The aims of this study were to find a rapid, easily screened and reproducible method for thederivation of EPCs from mouse embryonic stem cells (mESCs), and obtain VECs with high survival ratesand strong functions from the directed differentiation of the EPCs. The results showed that mESCs weredifferentiated into " stepping stone" -like progenitor cells with active proliferative ability by 10 ng / mLVEGF and 5 ng / mL bFGF. At the same time, the method of differential adherence was helpful for theselection of EPCs, and EPCs induced high expression of CD133 and CD34 (The relative expressionlevels were 0. 88 ± 0. 04 and 2. 12 ± 0. 02, respectively) for 3 days. Then EPCs were digested withacctuse enzymes, and induced to differentiate into vascular endothelial-like cells by 50 ng / mL VEGF and25 ng / mL bFGF for 7 days. The endothelial cells not only expressed endothelial marker genes (CD31, CD144, LAMA5, Tek, KDR and vWF),and marker proteins CD31, CD144 and LAMA5 (The relativeexpression levels were 1. 07 ± 0. 03, 0. 60 ± 0. 02 and 0. 70 ± 0. 02, respectively), but also had thegood ability of migration, tubulogenesis and formation of W-P bodies. Moreover, PBS, EPC and VECwere used to treat wounds of the same size. Both EPC and VEC could accelerate the degree of tissuehealing (The relative healing rates were 78. 93 ± 75. 35%, 95. 57 ± 83. 73% and 100. 00 ± 0. 00%, respectively), and VEC significantly enhanced the ability of wound angiogenesis and inflammatoryresponses. In consequence, this study preliminarily confirmed that mESC-derived EPCs coulddifferentiate into VECs after directional induction for 7 days, which had good function of tissue repair. The physiological pathway on stem cells by stimulating angiogenesis is expected to become a new target fortissue remodeling.
9.Identification of potential genes involved in biosynthesis of flavonoid and analysis of biosynthetic pathway in Fagopyrum dibotrys.
Xin WU ; Chen-Kai WANG ; Hai-Yan ZUO ; Zhao-Hui CHEN ; Sheng-Bing WU ; Mei-Qi ZHOU
China Journal of Chinese Materia Medica 2021;46(5):1084-1093
In order to enrich the transcriptome data of Fagopyrum dibotrys plants, analyze the genes encoding key enzyme involved in flavonoid biosynthesis pathway, and mine their functional genes, in this study, we performed RNA sequencing analysis for the rhizomes, roots, flowers, leaves and stems of F. dibotrys on the BGISEQ-500 sequencing platform. After de novo assembly of transcripts, a total of 205 619 unigenes were generated and 132 372 unigenes were obtained and annotated into seven public databases, of which, 81 327 unigenes were mapped to the GO database and most of the unigenes were annotated in cellular process, biological regulation, binding and catalytic activity. Besides, 86 922 unigenes were enriched in 136 pathways using KEGG database' and we identified 82 unigenes that encodes key enzymes involved in flavonoid biosynthesis. Comparing rhizome with root, flower, leaf or stem in F. dibotrys, 27 962 co-expressed differentially expressed genes(DEGs) were obtained. Among them, 23 515 DEGs of rhizome tissue-specific were enriched into 132 pathways and 13 unigenes were significantly enriched in biosynthesis of flavone and flavonol. In addition, we also identified 3 427 unigenes encoding 60 transcription factor(TFs) families as well as four unigenes encoding bHLH TFs were enriched in flavonoid biosynthesis. Our results greatly enriched the transcriptome database of plants, provided a reference for the analysis of key enzymes involved in flavonoid biosynthesis in plants, and will facilitate the study of the functions and regulatory mechanisms of key enzymes involved in flavonoid biosynthesis in F. dibotrys at the genetic level.
Biosynthetic Pathways/genetics*
;
Fagopyrum
;
Flavonoids
;
Flowers
;
Gene Expression Profiling
;
Gene Expression Regulation, Plant
;
Humans
;
Transcriptome/genetics*
10.Meta analysis of diseased bowel resection versus diversion enterostomy in the treatment of late severe complications of chronic radiation-induced rectal injury.
Zuo Lin ZHOU ; Yan Jiong HE ; Xiao Yan HUANG ; Teng Hui MA
Chinese Journal of Gastrointestinal Surgery 2021;24(11):1015-1023
Objective: To investigate the efficacy and safety of diseased bowel resection and diversion enterostomy in the treatment of late severe complications of chronic radiation-induced late rectal injury (RLRI). Methods: Studies about comparison of diseased bowel resection and diversion enterostomy in the treatment of late severe complications of chronic RLRI were screened and retrieved from databases, including PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, CNKI, VIP, CBM and Wanfang. The following terms in Chinese were used to search [Title/Abstract]: radiation-induced intestinal injury, radiation proctitis, surgery. The following English terms were used to search: Radiation-induced intestinal injury, Bowel injury from radiation, Radiation proctitis, Surgery, Colostomy. Literature inclusion criteria: (1) studies with control groups, published at home and abroad publicly, about the postoperative effects of diseased bowel resection vs. diversion enterostomy on RLRI patients with late severe complications; (2) the period of the study performed in the literatures must be clear; (3) patients at the preoperative diagnosis for RLRI with refractory bleeding, narrow, obstruction, perforation or fistula, etc.; (4) diseased bowel resection included Hartmann, Dixon, Bacon and Parks; diversion enterostomy included colostomy and ileostomy; (5) if the studies were published by the same institution or authors at the same time, the study with the biggest sample size was chosen; studies conducted in different time with different subjects were simultaneously included; (6) at least one prognostic indicator of the following parameters should be included: the improvement of symptoms, postoperative complications, mortality, and reversed stomas rate. The stoma reduction rate was defined as the ratio of successful closure of colostomy after diseased bowel resection and diversion enterostomy. The method of direct calculation or the method of convert into direct calculation were used for stoma reduction rate. Exclusion criteria: (1) a single-arm study without control group; (2) RLRI patients did not undergo diseased bowel resection or diversion enterostomy at the first time; (3) RLRI patients with distant metastasis; (4) the statistical method in the study was not appropriate; (5) the information was not complete, such as a lack of prognosis in the observational indexes. After screening literatures according to criteria, data retrieval and quality evaluation were carried out. Review Manager 5.3 software was used for Meta-analysis. Sensitivity analysis was used to exam the stability of results. Funnel diagram was used to analyze the bias of publication. Results: A total of 11 literatures were enrolled, including 426 RLRI patients with late severe complications, of whom 174 underwent diseased bowel resection (resection group) and 252 underwent diversion enterostomy (diversion group), respectively. Compared with diversion group, although resection group had a higher morbidity of complication (35.1% vs. 15.9%, OR=2.67, 95% CI: 1.58 to 4.53, P<0.001), but it was more advantageous in symptom improvement (94.2% vs. 64.1%, OR=6.19, 95% CI: 2.47 to 15.52, P<0.001) and stoma reductions (62.8% vs. 5.1%, OR=15.17, 95% CI: 1.21 to 189.74, P=0.030), and the differences were significant (both P<0.05). No significant difference in postoperative mortality was found between the two groups (10.1% vs. 18.8%, OR=0.74, 95% CI: 0.21 to 2.59, P=0.640). There were no obvious changes between the two groups after sensitivity analysis for the prognostic indicators (the symptoms improved, postoperative complications, mortality, and reversed stomas rate) compared with the meta-analysis results before exclusion, suggesting that the results were robust and credible. Funnel diagram analysis suggested a small published bias. Conclusions: Chronic RLRI patients with late severe complications undergoing diseased bowel resection have higher risk of complication, while their long-term mortality is comparable to those undergoing diversion enterostomy. Diseased bowel resection is better in postoperative improvement of symptoms and stoma reduction rate.
Colostomy
;
Enterostomy
;
Humans
;
Ileostomy
;
Radiation Injuries/surgery*
;
Rectum/surgery*
;
Surgical Stomas

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