1.Preparation of Phenolic Acid-sodium Hyaluronate Copolymers and in vitro Antioxidant Activity Assessment
Xiao-Yue ZHANG ; Xiao-Na WANG ; Min JIANG ; Ting-Ting HAN ; Jin-Song GONG ; Qing-Na LI ; Su-Zhen YANG ; Jin-Song SHI
Progress in Biochemistry and Biophysics 2024;51(8):1950-1962
ObjectiveSodium hyaluronate (HA) was used as the research object to modify it with phenolic acid in order to obtain the molecular structure with better antioxidant activity or even new activity. MethodsIn this study, 5 kinds of phenolic acid-sodium hyaluronate was prepared by free radical-mediated grafting method, and the grafts with the highest grafting degree were selected to optimize the synthesis conditions. Then, grafts structure and physicochemical properties were analyzed. The grafts were characterized by IR, UV, 1H NMR, FESEM and TGA spectra. The in vitro antioxidant capacity of grafts was determined by the scavenging ability of DPPH·, ABTS+· and O2-·. ResultsAmong 5 kinds of phenolic acid-sodium hyaluronate, the grafting rate of ferulic acid-sodium hyaluronate copolymer (FA-HA) was highest , which was chosen as experimental sample in the following tests. Firstly, the reaction conditions were investigated and the highest grafting rate was (16.59±0.31) mg/g at the optimal preparation conditions. Then, FA-HA structure and physicochemical properties were analyzed. Data from UV, IR, 1H NMR analyses, TGA showed that FA were successfully grafted to HA. Compared with HA, the results of gel permeation chrematography (GPC) showed that the molecular mass distribution ofFA-HA copolymer decreased from 34.4 to 31.5 ku, but the uniformity of molecular distribution was improved. FESEM results showed that the structure of copolymer exhibited a closely connected lamellar structure with a relatively smooth surface. TGA results showed that thermal stability of FA-HA had a little decline. The antioxidant performance in vitro results showed that, during 0.25-10 g/L, FA-HA can eliminate (83.76±4.86)% DPPH·, (76.95±5.06)% ABTS+· and (83.08±2.51)% O2-· respectively at 10 g/L. which were higher than that of native HA and FA. ConclusionFA and HA were successfully grafted together by free radical grafting, and the grafted FA-HA had better antioxidant activity in vitro, which provided a theoretical basis for further research and development of phenolic acid-HA grafts.
2.Analysis of fertility preservation and HPV negative conversion rate of LEEP by separating the vesicorectal space
Ting JIANG ; Yu XIE ; Ying-Xin GONG ; Yun-Qiang ZHANG ; Yue SHI ; Ruo-Yi GUO ; Qing WANG ; Xiao-Xia LIU
Fudan University Journal of Medical Sciences 2024;51(2):211-217
Objective To explore the eradication rate of human papillomavirus(HPV)and gestational outcome of patients with high-grade squamous intraepithelial disease of the cervix(HSIL)after loop electrosurgical excision procedure(LEEP)by transvaginal dissection of the vesicorectal form the cervix.Methods A total of 53 patients treated with LEEP by transvaginal dissection of the vesicorectal form the cervix in Obstetrics and Gynecology Hospital,Fudan University from Jan to Dec,2019 were investigated.Clinical information of cervical cytological examination,HPV test and cervical biopsy under colposcopy were followed up for 6,12 and 24 months post-LEEP were collected.HPV infection in these 53 patients were compared before and after LEEP surgery.The rate of successful fertility of the cohort,the HPV conversion rate of patients with hysterectomy and LEEP done were compared.The association between the pathological type and positive surgical margin and the association between HPV infection type and positive surgical margin were analyzed.Results HPV infection rate of was 94.3%(50/53)and the proportion of HPV16 and/or 18 infection was 75.5%(40/53).Mono-HPV infection rate(69.8%,37/53)was significantly higher than mixed HPV infection rate(22.7%,13/53).Thirty-eight patients(71.7%)were found with positive surgical margin in previous LEEP operation.Fifteen patients had recurrence(28.3%)and 40 patients(75.5%)successfully delivered baby after surgery.Postoperative pathology was mainly HSIL,accounting for 66%(30/53),and 28.3%patients(15/53)had no pathological change.Forty cases had satisfying fertility-conservative operation outcome with negative surgical margin,and 38 patients eradicated HPV infection after LEEP,which took up 95%of patients with satisfying fertility-conservative operation.There was no significant difference of positive resection margin rate in between groups of HPV16/18 infection and other types.Five cases had successful delivery(12.5%,5/40)with 1 case of vaginal delivery and 4 cases of cesarean section.Among these 5 cases,3 cases undertook preventive cervical cerclage,with 1 case of vaginal delivery and 2 cases of cesarean sections.Conclusion HPV eradication rate and surgical outcome could be significantly improved by LEEP with transvaginal dissection of the vesicorectal from the cervix,which satisfied the fertility preservation of females at reproductive age.
3.Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping
Hao DING-JUN ; Qin YUE ; Zhou SHI-JIE ; Dong BU-HUAI ; Yang JUN-SONG ; Zou PENG ; Wang LI-PING ; Zhao YUAN-TING
Journal of Pharmaceutical Analysis 2024;14(3):335-347
Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived car-diomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a po-tential reagent for repairing damaged hearts.
4.Exploration of a segmented training model for anesthesiology residents in key fiberoptic bronchoscopy techniques
Yuhao ZHANG ; Yanhua HUANG ; Qiang LI ; Yiqiong XU ; Qian GUO ; Yue XU ; Yan LUO ; Ting SHI ; Jun YAN
Chinese Journal of Medical Education Research 2024;23(10):1319-1325
Objective:To study the overall training effect of segmented training model on key fiberoptic bronchoscopy techniques for anesthesiology residents and the influence of key technique training order on the training effect.Methods:Different fiberoptic bronchoscopy simulators were used for specialized training in different key techniques of fiberoptic operation. To examine the effect of key technique learning order on the teaching effect, 40 anesthesiology residents who participated in fiberscope simulation training at Ruijin Hospital, Shanghai Jiaotong University School of Medicine between November 2022 and March 2023 were selected for this study. They were randomly divided into two groups (Group S and Group M) using a numerical table method. The teaching was completed using two orders of key techniques. The operation time, operation quality score, and theoretical knowledge mastery score of the two groups were recorded to compare the effect of key technique learning order on the mastery of fiberoptic skills. SPSS 29.0 statistical software was used for data analysis. Measurement data that conformed to normal distribution were expressed as mean ± standard deviation, and the independent samples t-test or Fisher's exact test were used for comparison between groups. The chi-square test was used for comparison of enumeration data. Results:After segmented training in each key technique, both groups of trainees were able to shorten the operation time of the corresponding key technique [SM simulator operation time (132.25±14.69) s vs. (49.80±4.46) s in group S, P<0.01; M simulator operation time (82.30±11.60) s vs. (57.10±6.77) s in group S, P<0.01; SM simulator operation time (83.10±10.62) s vs. (52.10±5.20) s in group M, P<0.01; M simulator operation time (132.25±14.69) s vs. (55.40±5.91) s in group M, P<0.01)]. Moreover, both groups showed a reduced number of wall touches [SM simulator wall touches (3.35±0.93) times vs. (0.65±0.49) times in group S, P<0.01; M simulator wall touches (2.50±1.05) times vs. (0.70±0.80) times in group S, P<0.01; SM simulator wall touches (1.55±1.15) times vs. (0.40±0.50) times in group M, P<0.01; M simulator wall touches (5.90±1.29) times vs. (1.10±0.79) times in group M, P<0.01]. There were no significant differences between the two groups in the performance score of fiberoptic-guided tracheal intubation after training [(92.50±5.97) points vs. (91.75±5.45) points] and in the lung segment localization time [(23.15±4.39) s, (21.40±4.84) s, (22.85±4.42) s vs. (22.75±5.11) s, (21.00±5.40) s, (21.50±5.10) s]. Conclusions:Segmented training on key fiberoptic bronchoscopy techniques is an effective model of fiberscope training for anesthesiology residents, and the order of training key techniques does not affect the effectiveness of training.
5.Varieties systematization and standards status analysis of fermented Chinese medicine.
Ting-Ting FU ; Xing-Bin YIN ; Meng-Ru CAI ; Rong-Yue ZHU ; Hua-Ting HUANG ; Shi-Lang LIAO ; Chang-Hai QU ; Xiao-Xu DONG ; Yue-Hua ZHOU ; Jian NI
China Journal of Chinese Materia Medica 2023;48(10):2699-2712
Fermented Chinese medicine has long been used. Amid the advance for preservation of experience, the connotation of fermented Chinese medicine has been enriched and improved. However, fermented Chinese medicine prescriptions generally contain a lot of medicinals. The fermentation process is complicated and the conventional fermentation conditions fail to be strictly controlled. In addition, the judgment of the fermentation end point is highly subjective. As a result, quality of fermented Chinese medicine is of great difference among regions and unstable. At the moment, the quality standards of fermented Chinese medicine are generally outdated and different among regions, with simple quality control methods and lacking objective safe fermentation-specific evaluation indictors. It is difficult to comprehensively evaluate and control the quality of fermented medicine. These problems have aroused concern in the industry and also affected the clinical application of fermented Chinese medicine. This article summarized and analyzed the application, quality standards, and the modernization of fermentation technology and quality control methods of fermented Chinese medicine and proposed suggestions for improving the quality standards of the medicine, with a view to improving the overall quality of it.
Medicine, Chinese Traditional
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Reference Standards
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Quality Control
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Fermentation
6.Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C
Ping ZHU ; Shi-You LI ; Jin DING ; Zhou FEI ; Sheng-Nan SUN ; Zhao-Hui ZHENG ; Ding WEI ; Jun JIANG ; Jin-Lin MIAO ; San-Zhong LI ; Xing LUO ; Kui ZHANG ; Bin WANG ; Kun ZHANG ; Su PU ; Qian-Ting WANG ; Xin-Yue ZHANG ; Gao-Liu WEN ; Jun O.LIU ; Thomas-John AUGUST ; Huijie BIAN ; Zhi-Nan CHEN ; You-Wen HE
Journal of Pharmaceutical Analysis 2023;13(6):616-624
Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.
7.Cholesterol paradox in the community-living old adults: is higher better?
Sheng-Shu WANG ; Shan-Shan YANG ; Chun-Jiang PAN ; Jian-Hua WANG ; Hao-Wei LI ; Shi-Min CHEN ; Jun-Kai HAO ; Xue-Hang LI ; Rong-Rong LI ; Bo-Yan LI ; Jun-Han YANG ; Yue-Ting SHI ; Huai-Hao LI ; Ying-Hui BAO ; Wen-Chang WANG ; Sheng-Yan DU ; Yao HE ; Chun-Lin LI ; Miao LIU
Journal of Geriatric Cardiology 2023;20(12):837-844
OBJECTIVE:
To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.
METHODS:
A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators.
RESULTS:
A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death.
CONCLUSIONS
In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.
8. Artesunate inhibits development of breast cancer cells via affecting expression of Skp2 and CDKN1A
Li-Ting SUN ; Guan-Tong SHEN ; Fei ZHU ; Jing KANG ; Jing YUE ; Ru-Yi SHI ; Xiao-Ling HU ; Nan QIN ; Ke LIAN ; Jing KANG ; Jing YUE
Chinese Pharmacological Bulletin 2023;39(9):1675-1681
Aim To explore the effect of artesunate (ART) on the function of breast cancer cells during the progression of breast cancer and the possible mechanism of action. Methods MCF-7 (30 μmol • L-
9. Prevention and inhibition of nasopharyngeal carcinoma growth by attenuated salmonella SGN1
Yun-Hao LAI ; Ting-Qi HUANG ; Shi LIU ; Yue-Rong PENG ; Fang-Hong LI ; Zheng-Gang ZHAO ; Su-Jin ZHOU ; Zi-Jian ZHAO ; Qi-Ting TAN ; Jia-Luo MAI
Chinese Pharmacological Bulletin 2023;39(10):1867-1873
Aim To study the inhibitory effect of attenuated salmonella SGN1, overexpressing methioninase, on nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods The cell proliferation, cell cycle, cell apoptosis, clony formation and migration a-bility of 5-8F, HNE-2, CNE-2 cells were measured u-sing flow cytometry assay, clone formation assay, and wound assay after the methionine restriction treatment. 5-8F, HNE-2, CNE-2 cells were infected with SGN1 at the multiplicity of infection (MOI) of 1: 100 for 5 hours, followed with the measurement of cell growth. A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma. Results Compared with the control group, methionine restriction significantly inhibited the proliferation, migration ability, and clone formation of nasopharyngeal carcinoma cells and blocked the G
10.Regulatory effect of five-element music therapy of traditional Chinese medicine for suboptimal health status of liver stagnation and spleen deficiency based on the temperature changes of acupoints.
Jing-Yu ZHANG ; Bo JI ; Yi-Tian LIU ; Yang FANG ; Tian-Yu SHI ; Qian-Wei LIU ; Yun-Peng GE ; Jia-Jia WANG ; Zi-Yue ZHANG ; Na-Na HAN ; Yu-Ting LIU ; Shi-Dong ZOU
Chinese Acupuncture & Moxibustion 2022;42(11):1253-1259
OBJECTIVE:
To observe the effect of five-element music therapy of traditional Chinese medicine (TCM) on the clinical symptoms and the quality of life in the patients with suboptimal health status (SHS) of liver stagnation and spleen deficiency and explore the corresponding specificity changes in the temperature of acupoints when zangfu functions are of dysfunction and recovered to be balanced, separately.
METHODS:
Sixty patients with SHS of liver stagnation and spleen deficiency were randomized into an observation group and a control group, 30 cases in each one. In the control group, the conventional health education was provided. In the observation group, on the base of the therapeutic regimen as the control group, the patients received the five-element music therapy to pacify the liver qi and strengthen the spleen functions, once every two days, 30 min each time, 3 treatments a week. The course of treatment consisted of 4 weeks. Before and after treatment, the TCM syndrome score and the MOS 36-item short form healthy survey (SF-36) score were compared between the two groups and the clinical therapeutic effect was evaluated. Using infrared thermal imaging, the temperature at the acupoints of the affected organs (liver, spleen), the related organs (gallbladder, stomach) and the other non-related zangfu organs (pericardium, lung) was detected before and after treatment in the two groups.
RESULTS:
After treatment, the TCM syndrome scores were reduced when compared with those before treatment in the two groups (P<0.01, P<0.05); the reduction in the observation group was larger than that of the control group (P<0.01). The score of each domain for the SF-36 in the observation group and the score of role-emotional domain in the control group were all increased when compared with the scores before treatment (P<0.01, P<0.05); and the score of each domain for the SF-36 in the observation group was higher than that in the control group (P<0.01). The total effective rate was 66.7% (20/30) in the observation group, which was higher than 10.0% in the control group (3/30, P<0.05). In the observation group, the temperature of the yuan-primary point, the back-shu point and the front-mu point related to the liver, as well as those related to the gallbladder after treatment was reduced when compared with the temperature before treatment; and the changes were larger than those of the control group (P<0.01). The temperature of the yuan-primary point, the back-shu point and the front-mu point related to the spleen, as well as the back-shu point and the front-mu point related to the stomach in the observation group was increased when compared with the temperature before treatment (P<0.01); and the changes were larger than those of the control group (P<0.01). For the temperature of the non-specific points related to the liver and spleen, as well as the yuan-primary point, the back-shu point and the front-mu point related to the pericardium and the lung, there was no significant differences when compared with the temperature at the above-mentioned acupoints before and after treatment (P>0.05).
CONCLUSION
TCM five-element music therapy associated with the conventional health education may effectively relieve the clinical symptoms and improve the quality of life in the patients with suboptimal health status of liver stagnation and sleep deficiency; and the therapeutic effect is better than the simple health education. The changes in the temperature of acupoints may reflect the functional regulation of the related zangfu organs in the body.
Humans
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Acupuncture Points
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Medicine, Chinese Traditional
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Spleen
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Music Therapy
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Quality of Life
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Temperature
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Liver
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Health Status

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