1.Effect and mechanism of tetramethylpyrazine regulating ferroptosis in rats with spinal cord injury
Jingwei TAO ; Jingya ZHOU ; Yi ZHAO ; Jingpei REN ; Chuanyu HU ; Lin XU ; Xiaohong MU ; Xiao FAN
Chinese Journal of Tissue Engineering Research 2024;28(26):4158-4163
BACKGROUND:Studies have shown that there is a close association between spinal cord injury and ferroptosis,and that tetramethylpyrazine has the function of regulating redox reactions. OBJECTIVE:To investigate the regulatory effect of tetramethylpyrazine on ferroptosis in rats with spinal cord injury and its mechanism. METHODS:Thirty-six female specific pathogen-free Sprague-Dawley rats were randomly divided into sham-operated group,model group and tetramethylpyrazine group,with 12 rats in each group.Animal models of spinal cord injury were established using the modified Allen's method in the latter two groups.No treatment was given in the sham-operated group,while rats in the model and tetramethylpyrazine groups were given intraperitoneal injection of normal saline and tetramethylpyrazine solution,once a day,for 28 days. RESULTS AND CONCLUSION:The Basso,Beattie&Bresnahan Locomotor Rating Scale score in the tetramethylpyrazine group was lower than that in the sham-operated group but higher than that in the model group after 14,21,and 28 days of treatment(P<0.05).After 28 days of treatment,hematoxylin-eosin staining showed that in the model group,the spinal cord tissue of rats showed cavity formation,necrotic tissue and inflammatory infiltration with fibrous tissue formation;in the tetramethylpyrazine group,the area of spinal cord tissue defects was smaller,and inflammatory infiltration and fibrous tissue formation were less than those in the model group.After 28 days of treatment,Prussian blue staining showed that a large amount of iron deposition was seen in the spinal cord tissue of rats in the model group,and less iron deposition was seen in the spinal cord tissue of rats in the tetramethylpyrazine group than in the model group.After 28 days of treatment,the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were decreased(P<0.05)and the level of malondialdehyde was increased in the model group compared with the sham-operated group(P<0.05);the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were increased(P<0.05)and the level of malondialdehyde was decreased in the tetramethylpyrazine group compared with the model group(P<0.05).After 28 days of treatment,qRT-PCR and western blot assay showed that the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the model group were decreased compared with those in the sham-operated group(P<0.05),while the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the tetramethylpyrazine group were increased compared with those in the model group(P<0.05).Immunofluorescence staining showed that after 28 days of treatment,the neuronal nuclei positive staining in the spinal cord of rats was the most in the sham-operated group and the least in the model group.To conclude,tetramethylpyrazine can improve motor function and play a neuroprotective role in rats with spinal cord injury by regulating ferroptosis.
2.Study on the Prevalence Difference between Northwest Dryness Syndrome and Blood Stasis Syndrome of Coronary Heart Disease and the Correlation with Major Adverse Cardiovascular Events
Xintong LI ; Peng LI ; Changgeng FU ; Linzi LONG ; Jingya ZHOU ; Jiawei HU ; Yutai ZHAO
Journal of Traditional Chinese Medicine 2024;65(12):1255-1261
ObjectiveTo explore the prevalence difference between northwest dryness syndrome and blood stasis syndrome of coronary heart disease (CAD) and their correlations with major adverse cardiovascular events (MACE). MethodsThe medical records including general information and risk factors for vascular diseases (gender, age, smoking history, diabetes history, hypertension history, chronic kidney disease history and body mass index), laboratory indicators (fasting blood glucose, triglyceride, high density lipoprotein cholesterol, etc.) of 499 CAD patients in the Department of Cardiology of the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University from November 1st, 2015 to September 30th,2020 were collected, and whether they suffered from northwest dryness syndrome or blood stasis syndrome was judged. The incidence of MACE was followed up for one year. The differences of cardiovascular risk factors between the northwest dryness syndrome and blood stasis syndrome of CAD were compared, and the correlation with MACE was analyzed. ResultsAmong the 499 CAD patients, there were 128 cases (25.65%) of simple blood stasis syndrome, 33 cases (6.61%) of simple northwest dryness syndrome, 209 cases (41.88%) of northwest dryness syndrome plus blood stasis syndrome, and 129 (25.85%) cases of not blood statis syndrom either northwest dryness syndrome. Univariate regression analysis showed that smoking history, diabetes history, fasting blood glucose abnormality, triglyceride abnormality, and high density lipoprotein cholesterol abnormality were positively correlated with northwest dryness syndrome in CAD patients (OR>1, P<0.05), while smoking history, abnormal triglyceride and abnormal high density lipoprotein cholesterol were positively correlated with blood stasis syndrome in CAD patients (OR>1, P<0.05). Multivariate regression analysis showed that the history of diabetes, abnormal triglyceride and abnormal high density lipoprotein cholesterol were positively correlated with northwest dryness syndrome of CAD (P<0.05). Smoking history, abnormal triglycerides and abnormal high density lipoprotein cholesterol were positively correlated with blood stasis syndrome (P<0.05). Association rule analysis showed that the confidence of CAD patients with northwest dryness syndrome complicated with blood stasis syndrome was 86.36%, and that of patients with blood stasis syndrome complicated with northwest dryness syndrome was 62.02%. Among the 499 patients, 96 had MACE in one year, accounting for 19.24% of the total. Logistics regression analysis showed that the correlation with incidence of MACE in CAD patients within one year from strong to weak was northwest dryness syndrome plus blood stasis syndrome [OR = 5.113, 95%CI (3.118, 8.387), P<0.001)], blood stasis syndrome[OR = 4.630, 95%CI (2.394, 8.955), P<0.001], northwest dryness syndrome [OR = 4.395, 95%CI (2.642, 7.309), P<0.001]. ConclusionBlood stasis syndrome is the main syndrome type of CAD in Xinjiang Uygur Autonomous Region. CAD patients with northwest dryness syndrome are more likely to have blood stasis syndrome, and most suffer from both northwest dryness syndrome and blood stasis syndrome simultaneously. There is the strongest correlation between northwest dryness syndrome plus blood stasis syndrome and 1-year occurrence of MACE in CAD.
3.Methodology for Developing Rapid and Living Guidelines of Traditional Chinese Medicine (RALIG-TCM) (Part 3): Rapid Evidence Collection, Integration and Recommendation Formation
Ziteng HU ; Lijiao YAN ; Yujing ZHANG ; Yaxin CHEN ; Xiaoling LI ; Haili ZHANG ; Huizhen LI ; Jingya WANG ; An LI ; Zhao CHEN ; Ning LIANG ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(3):281-286
The lack of direct evidence is an important problem faced in the formation of recommendations in rapid living guidelines of traditional Chinese medicine under public health emergencies, and the supplementation of indirect evidence can be a key method to solve this problem. For the collection of evidence, the type of evidence required, including direct and indirect evidence, should be clarified, and ‘direct first’ principle for selecting evidence can be set to standardize and accelerate the guideline development. When integrating evidence, recommendations can be formed directly if there is sufficient direct evidence, while regarding insufficient direct evidence, recommendations need to be supplemented and improved by integrating indirect evidence. In addition, when the body of evidence contains evidence from multiple sources, it is suggested to rate the evidence according to “higher rather than lower” principle. Finally, when forming recommendations, the level of evidence, safety and economic efficiency should be taken into consideration to determine the strength of the recommendation.
4.Factors Influencing Inpatient Costs for Patients Undergoing Surgery for Intrauterine Lesions under DRG Payment
Yutong WANG ; Weiguo ZHU ; Xueqin SUN ; Jiali TONG ; Jingya ZHOU ; Qing ZHAO ; Bocheng LI ; Wei ZHANG ; Xiaokun LIU ; Rui DONG ; Chen XIE ; Ding HAN
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1069-1076
To analyze the factors affecting the cost of hospitalization for patients and provide insights using the intrauterine lesion surgery group (DRG code NE19) as an example. This study was a retrospective cross-sectional study, with data from the first page of medical records of patients enrolled under NE19 at a comprehensive tertiary hospital in Beijing from March 15, 2022 to November 30, 2023. Influence factor selection and multifactorial linear regression analysis were conducted with hospitalization cost as the dependent variable, and patient's basic information, treatment information and key concern factors as independent variables. The profit and loss of medical records containing key factors and differences in indicators of hospitalization cost structure were analyzed in the context of clinical practice. A total of 2213 valid medical records (all female patients) were included, with patients predominantly young and middle-aged women under 45 years of age (72.12%), and with 931 day surgery medical records (42.07%). The diagnosis records included 334(15.09%) multiple uterine leiomyomas, and 246(11.12%) pelvic adhesions. A total of 150(6.78%) medical records involved ovary- and tubal-related surgeries or manipulations, with 160(7.23%) main operations being laparoscopic hysterectomy of diseased uterine lesions and 38(1.72%) mechanical rotational excision of abnormal uterine tissue using transhysteroscopy. Linear regression analysis showed that whether or not ovarian and tubal surgical operations were involved ( The NE19 group of hospitals in the study had a high loss rate, and factors such as the severity of the patient's condition and the use of new technologies affected hospitalization costs, suggesting that there is room for further optimization of the existing grouping scheme. Tiered payment standards can be set up for different tiers of healthcare institutions, and a sound and optimized exclusion mechanism can be used to promote the development of new technologies. The internal management of hospitals should encourage the development of daytime surgery to improve the efficiency of medical services.
5.Contemporary strategies and approaches for characterizing composition and enhancing biofilm penetration targeting bacterial extracellular polymeric substances
Lu LAN ; Zhao YUTING ; Li MINGXING ; Wang XIAOBO ; Zhu JIE ; Liao LI ; Wang JINGYA
Journal of Pharmaceutical Analysis 2024;14(4):506-524
Extracellular polymeric substances(EPS)constitutes crucial elements within bacterial biofilms,facili-tating accelerated antimicrobial resistance and conferring defense against the host's immune cells.Developing precise and effective antibiofilm approaches and strategies,tailored to the specific charac-teristics of EPS composition,can offer valuable insights for the creation of novel antimicrobial drugs.This,in turn,holds the potential to mitigate the alarming issue of bacterial drug resistance.Current analysis of EPS compositions relies heavily on colorimetric approaches with a significant bias,which is likely due to the selection of a standard compound and the cross-interference of various EPS compounds.Considering the pivotal role of EPS in biofilm functionality,it is imperative for EPS research to delve deeper into the analysis of intricate compositions,moving beyond the current focus on polymeric materials.This ne-cessitates a shift from heavy reliance on colorimetric analytic methods to more comprehensive and nuanced analytical approaches.In this study,we have provided a comprehensive summary of existing analytical methods utilized in the characterization of EPS compositions.Additionally,novel strategies aimed at targeting EPS to enhance biofilm penetration were explored,with a specific focus on high-lighting the limitations associated with colorimetric methods.Furthermore,we have outlined the challenges faced in identifying additional components of EPS and propose a prospective research plan to address these challenges.This review has the potential to guide future researchers in the search for novel compounds capable of suppressing EPS,thereby inhibiting biofilm formation.This insight opens up a new avenue for exploration within this research domain.
6.Application of situational simulation combined with the debriefing-GAS method in the teaching of prenatal genetic counseling
Jingyu LIU ; Jingya ZHAO ; Xuan HUANG ; Linhuan HUANG ; Zhiming HE ; Yanmin LUO ; Haitian CHEN ; Yi ZHOU
Chinese Journal of Medical Education Research 2024;23(5):677-682
Objective:To investigate the application effect of situational simulation combined with the Debriefing-GAS method in the teaching of prenatal genetic counseling.Methods:A total of 30 medical students of the five- and eight-year programs in the classes of 2017 and 2018 who received genetic counseling training in The First Affiliated Hospital of Sun Yat-sen University from May 2021 to May 2022 were selected as research subjects, and situational simulation combined with the debriefing-GAS method was used for the teaching of prenatal genetic counseling. Assessment was performed by the teacher to evaluate the change in genetic counseling abilities during the teaching process, and a questionnaire survey was conducted to investigate the degree of satisfaction with teaching among the students. SPSS 26.0 software was used for data analysis; normally distributed continuous data were expressed as mean±standard deviation, non-normally distributed continuous data were expressed as M d(P 25,P75), and categorical data were expressed as frequency and rate; the paired samples t-test was used for comparison of assessment scores before and after teaching. Results:After teaching, there were significant increases in the assessment scores of genetic counseling [(74.5±18.6) points vs. (87.2±14.5) points, t=4.10, P<0.001] and comprehensive abilities such as clinical ability [(35.4±9.6) points vs. (41.1±6.9) points, t=3.72, P=0.001], doctor-patient communication [(17.5±4.6) points vs. (20.8±3.8) points, t=4.34, P<0.001], professional literacy [(11.0±2.5) points vs. (12.5±2.3) points, t=2.89, P=0.007], teamwork [(3.5±1.0) points vs. (4.2±0.8) points, t=3.67, P=0.001], and organizational effectiveness [(7.1±2.0) points vs. (8.3±1.7) points, t=2.94, P=0.006]. The questionnaire survey showed that the degree of satisfaction among students was rated above satisfaction for the reasonability of the implementation process and links of genetic counseling teaching [3.0 (3.0, 4.0) points], teaching quality [3.5 (3.0, 4.0) points], whether the teaching model could effectively increase the interest and initiative in learning [4.0 (3.0, 4.0) points], the improvement in theoretical knowledge [4.0 (3.0, 4.0) points], communication skills in genetic counseling [3.0 (3.0, 4.0) points], and the understanding of related techniques and application prospect [3.0 (3.0, 4.0) points]. However, two students (6.7%) thought that this teaching model could not efficiently reach teaching objectives, since the teaching process was slightly complicated. Conclusions:Situational simulation combined with the debriefing-GAS method has achieved a good effect in the teaching of prenatal genetic counseling and can help undergraduates to master the theoretical knowledge of prenatal genetic counseling and improve their comprehensive clinical abilities, with a relatively high degree of satisfaction, and therefore, it holds promise for clinical application.
7.Effects of selective feticide by radiofrequency ablation and risk factors for prognosis in 75 twins complicated by selective intrauterine growth restriction
Jingyu LIU ; Quanrui LIU ; Jingya ZHAO ; Yi ZHOU
Chinese Journal of Perinatal Medicine 2023;26(4):277-285
Objective:To analyze the effects of selective feticide by radiofrequency ablation (RFA) and the risk factors for adverse pregnancy outcomes in twins complicated by selective intrauterine growth restriction (sIUGR) and evaluate the neurodevelopment in live births during a short-term follow-up.Methods:This study retrospectively enrolled 75 twins with sIUGR who underwent RFA for selective feticide and were delivered in the First Affiliated Hospital of Sun Yat-sen University between January 1, 2017 and March 31, 2022. According to the gestational age at the procedure, they were divided into three groups including 16-19 +6 weeks of gestation (Group A, n=16), 20-23 +6 weeks of gestation (Group B, n=44) and ≥24 weeks of gestation (Group C, n=15). They were also grouped according to the presence or absence of twin-twin transfusion syndrome (TTTS): sIUGR with TTTS group ( n=36) and isolated sIUGR group ( n=39). The 39 cases in the isolated sIUGR group were further divided into three groups according to the Doppler flow in the smaller co-twin: type Ⅰ ( n=3), type Ⅱ ( n=27) and type Ⅲ ( n=9). According to pregnancy outcomes, the 75 cases were divided into adverse pregnancy outcome group ( n=49) and non-adverse pregnancy outcome group ( n=26). Statistical analysis was performed using two independent sample t-test, one-way analysis of variance and LSD test, nonparametric test and Nemenyi test, as well as Chi-square test and Fisher's exact test to compare the difference in clinical characteristics and perinatal outcomes among groups. Kaplan-Meier survival curves and Log-rank test were used to analyze the duration of pregnancy after the procedure. Univariate logistic regression analysis was used to identify the risk factors for adverse pregnancy outcomes. Results:(1) The gestational age at the time of procedure was (21.9±2.3) weeks (16.6-26.0 weeks) for all cases. The intertwin estimated fetal weight discordance (ΔEFW) was less and the duration of RFA was shorter in group A than in group B or C [(27.8±8.4)% vs (36.2±12.0)% and (39.8±15.5)%; 7 min (5-14 min) vs 10 min (5-16 min) and 12 min (8-18 min); LSD test or Nemenyi test, P<0.017]. The incidence of TTTS was higher in group A than in group B or C [12/16 vs 43% (19/44) and 5/15; Bonferroni correction, P<0.017]. There was no significant difference in the incidence of premature rupture of membrane, spontaneous abortion, fetal demise, premature delivery and gestational age at delivery between Group A, B and C (all P>0.05). (2) Compared with the isolated sIUGR group, the sIUGR with TTTS group showed less ΔEFW [(29.6±11.4)% vs (40.1±11.8)%, t=3.88, P<0.001], higher incidence of premature rupture of membrane [47% (17/36) vs 21% (8/39), χ2=6.01, P=0.014], lower rate of live births [69% (25/36) vs 95%(37/39), χ2=8.45, P=0.004] and earlier delivery [34.1 weeks (26.7-40.7 weeks) vs 38.0 weeks (29.3-40.0 weeks), Z=311.50, P=0.018]. (3) There was no significant difference in the incidence of premature rupture of membrane, live birth rate or 30-day survival rate among the sIUGR type Ⅰ, Ⅱ and Ⅲ groups (all P>0.05). (4) sIUGR complicated by TTTS was a risk factor for adverse pregnancy outcomes of the co-twin after the procedure ( OR=3.94, 95% CI: 1.40-11.10, P=0.010). (5) Thirteen co-twins presented with cardiac enlargement, myocardial hypertrophy or/and tricuspid regurgitation in routine ultrasound scans before the procedure and nine of them had TTTS. Among them, eight live births were followed up for one month to 4.5 years of age and no abnormality in cardiac function was reported. (6) There were overall 62 live births. Apart from two cases of neonatal death and four lost to follow-up, the other 56 cases were followed up to one month to 5 years of age and two premature infants showed gross motor retardation. Conclusions:The gestational age at RFA has no significant impact on pregnancy outcomes, while sIUGR complicated by TTTS may increase the risk of adverse outcomes after the procedure. After RFA, the overall survival rate of the co-twin in pregnancies with sIUGR is high and no severe neurodevelopmental abnormalities has been found during a short-term follow-up.
8.Clinical value of different genetic testing methods for detection of true fetal chromosome mosaicism
Meijiao SHANG ; Quanrui LIU ; Jianzhu WU ; Jingyu LIU ; Jingya ZHAO ; Shaobin LIN ; Yi ZHOU
Chinese Journal of Perinatal Medicine 2023;26(4):292-297
Objective:To investigate the performance of chromosome karyotype, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) in prenatal diagnosis of true fetal chromosome mosaicism. Methods:This retrospective study enrolled 40 women with true fetal chromosome mosaicism from 4 071 singleton pregnant women who were indicated for and underwent amniocentesis or/and cordocentesis in the the First Affiliated Hospital of Sun Yat-sen University from April 2018 to August 2021. The results of chromosome karyotyping, CMA and FISH, the types of chromosomal mosaicism, mosaicism ratio and pregnancy outcomes were analyzed using Chi-square test. Results:(1) The detection rate of true fetal mosaicism was 0.98% (40/4 071). (2) Sex chromosome mosaicism accounted for 42.5% (17/40). Other chromosomal mosaicism involved chromosomes 21, 22, 18, 16, 7, 12, 15, 17 and 20, as well as balanced chromosomal translocation. (3) The detection rate of true fetal mosaicism by chromosome karyotyping was 77.4% (24/31) from amniotic fluid samples and 10/19 from umbilical cord blood samples, while that data by CMA was 76.7% (23/30) and 7/11,respectively. (4) Of the 40 pregnant women with fetal chromosome mosaicism, FISH test was performed on 20 cases (14 cases were verified with both amniotic fluid and umbilical cord blood samples, five with amniotic fluid samples and one with umbilical cord blood sample), and all of the diagnosis of mosaicism were confirmed. For those with mosaicism ratio <30%, the detection rate by FISH was higher than that by CMA among amniotic fluid samples [14/19 vs 43.5% (10/23), χ2=3.88, P=0.049]. (5) Among the 40 pregnant women, five were lost to follow-up; 18 chose to terminate the pregnancy; and 17 continued the pregnancy to delivery. No abnormalities in mental or physical development were reported in the 17 neonates after birth or during on-line follow-up between 6 to 24 months old. Of the 14 pregnant women with mosaicism ratio <30% which confirmed by FISH, eight chose to continue the pregnancy, and no abnormalities in mental development or growth were found in the neonates. Conclusions:In prenatal diagnosis of true fetal choromosome mosaicism, the incidence of sex chromosome mosaicism is the highest. FISH may improve the prenatal diagnosis rate of mosaicism and is more accurate in determining the mosaicism ratio. The combination of FISH, CMA and chromosome karyotyping would significantly improve the detection rate of chromosomal mosaicism and assess the mosaicism ratio more accurately, which is of great value in clinical consultation and evaluation of fetal prognosis.
9.A hybrid bacterium with tumor-associated macrophage polarization for enhanced photothermal-immunotherapy.
Jingya ZHAO ; Huabei HUANG ; Jinyan ZHAO ; Xiang XIONG ; Sibo ZHENG ; Xiaoqing WEI ; Shaobing ZHOU
Acta Pharmaceutica Sinica B 2022;12(6):2683-2694
Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages (TAMs) and increasing the immunogenicity of tumors via immunogenic cell death (ICD) have been emerging as promising anticancer immunotherapy strategies. However, the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging. To overcome these dilemmas, a hybrid bacterium with tumor targeting and penetration, TAM polarization, and photothermal conversion capabilities is developed for improving antitumor immunotherapy in vivo. The hybrid bacteria (B.b@QDs) are prepared by loading Ag2S quantum dots (QDs) on the Bifidobacterium bifidum (B.b) through electrostatic interactions. The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues, enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment. It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photothermal effect of the QDs, resulting in an enhanced immune effect. This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.
10.Research advances in the protective effect of sulforaphane against liver injury and related mechanisms
Xinyu MA ; Tingting DUAN ; Jingya XU ; Jiahe ZHAO ; Chunlei ZHANG ; Baolong LI
Journal of Clinical Hepatology 2022;38(1):206-209
Sulforaphane is a phytochemical with a variety of biological activities that exists widely in Cruciferae plants. This article summarizes the recent experimental studies of sulforaphane in the treatment of various types of liver injury in China and globally and reviews the role and mechanism of sulforaphane in protecting against liver injury. Based on the experimental animal models of liver injury, this article summarizes the therapeutic effect of sulforaphane on the models of chemical liver injury, drug-induced liver injury, alcoholic liver injury, immunological liver injury, and ischemia/reperfusion liver injury and analyzes the mechanism of action of sulforaphane in improving experimental liver injury, so as to provide a reference for in-depth research on sulforaphane in protecting against liver injury.

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