摘要
Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".
Subject(s)
Humans , Retrospective Studies , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Drugs, Chinese Herbal/therapeutic use , Sesquiterpenes/therapeutic use摘要
Purpose To explore the diagnostic efficiency of ultrasound(US)combined with contrast-enhanced ultrasound(CEUS)in breast lesions and to analyze the related factors affecting the diagnostic accuracy.Materials and Methods From January 2022 to February 2023,the clinical data and ultrasound images of 784 patients who underwent breast US and CEUS examination with definite pathological results were retrospectively collected in the First Medical Center of the PLA General Hospital.The diagnostic efficacy of US combined with CEUS in benign and malignant breast lesions was analyzed,respectively.The independent risk factors for diagnostic errors were analyzed via Logistic regression.Results The sensitivity,specificity and accuracy of US combined with CEUS in the diagnosis of benign and malignant breast lesions were 89.2%,84.4%and 88.7%,respectively.The area under the receiver operating characteristic curve was 0.932.The results of multivariate Logistic regression analysis showed that the diagnosis error rate increased when the lesions were non-mass type(odds ratio,OR=1.927,P=0.047),complex cystic and solid(OR=3.729,P=0.000),and high-enhanced CEUS(OR=1.937,P=0.023),while the diagnosis error rate decreased when the lesions were large(OR=0.688,P=0.004)and with US-detect suspicious lymph node(OR=0.143,P=0.011).Conclusion When the breast lesions are non-mass type,complex cystic and solid lesions and hyper-enhancement,the diagnosis error rate of US combined with CEUS increased.It is necessary to further explore the enhancement patterns of different lesions.
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Purpose To explore the correlation between phosphatidylinositol 3 kinase/serine-threonine kinase(PI3K/AKT)signaling pathway and elastic characteristics of breast lesions.Materials and Methods A total of 115 breast lesions were prospectively analyzed in 114 patients who underwent surgery from May 2021 to May 2022 at Chinese PLA General Hospital.Ultrasound and shear wave elastography were performed preoperatively.Immunohistochemical staining was used to detect the expression of PI3K/AKT protein levels in the tissue specimens,and the correlation between the staining results and the elastic parameters of shear wave elastography was analyzed.Results Surgical pathology revealed benign breast lesions in 50 cases and malignant lesions in 65 cases(25 cases with axillary lymph node metastasis).The maximum modulus of elasticity(F=40.47),the average modulus of elasticity(F=45.11),the ratio of elasticity of the lesion to that of the surrounding tissue(F=48.98),the detection rate of"hard ring sign"(χ2=62.25),the expression level of PI3K/p-PI3K(F=15.19,58.95)and AKT/p-AKT(F=46.94,74.21)were found in benign and malignant lesions without axillary lymph node metastasis,malignant lesions with axillary lymph node metastasis(all P<0.05).The expression levels of PI3K/p-PI3K and AKT/p-AKT were positively correlated with the maximum elastic modulus value,the mean elastic modulus value,and the ratio of elasticity of the lesion to the surrounding tissues(r=0.475,0.475,0.451;r=0.533,0.540,0.542;r=0.371,0.402,0.445;r=0.482,0.455,0.545,all P<0.05).Conclusion The expression level of PI3K/AKT in breast lesions is correlated with elastic characteristics,suggesting that it plays an important role in the regulation of elastic characteristics of breast lesions.
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Objective To analyze the factors related to early allograft dysfunction(EAD)after liver transplantation and to construct a predictive model.Methods A total of 375 patients who underwent liver transplantation in our hospital from December 2008 to December 2021 were collected,including 90 patients with EAD and 266 patients without EAD.Thirty items of baseline data for the 2 groups were compared and analyzed.Aftergrouping in a ratio of 7∶3,univariate and multivariate logistic regression analyses were used in the training set to evaluate the factors related to EAD and construct a nomogram.Receiver operating characteristic(ROC)curve,decision curve analysis(DCA),sensitivity,specificity,positive predictive value,negative predictive value,Kappa value and other indicators were used to evaluate the model performance.Results The incidence of EAD after liver transplantation was 24%.Multivariate logistic regression analysis showed that preoperative tumor recurrence history(OR=3.15,95%CI:1.28～7.77,P=0.013)and operation time(OR=1.22,95%CI:1.04～1.42,P=0.015)were related to the occurrence of EAD after surgery.After predicting the outcome according to the cut-off point of 0.519 identified by the Youden index,the model performance in the both training set and validation set was acceptable.DCA suggested the model has good clinical applicability.Conclusion The risk factors for EAD after liver transplantation are preoperative tumor recurrence history and operation time,and the established model has predictive effect on prognosis.
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Objective To analyze the risk factors for severe illness caused by coronavirus disease 2019 in Fuzhou city.Methods The data of 4081 confirmed cases with current address in Fuzhou was collected from China Information System for Disease Control and Prevention from January 1 to June 30,2023.The epidemiological data of those cases was investigated such as the demographic characteristics,clinical manifestations and past medical history,etc.The risk factors of severe cases were analyzed by using the logistic regression.Results 4081 confirmed cases had been reported including 671 severe cases and 3410 non-severe cases.The demographic characteristics of severe cases,such as the proportion of male,age and current address in community were higher than that of non-severe cases,vaccination rate was lower than non-severe cases(59.02%vs.80.12%),the differences are statistically significant(P＜0.001).The clinical manifestations such as interval time between onset and visit(P=0.001),fever(P=0.002),difficulty in breathing/shortness of breath(P=0.001)were the factors related to severe illness.The past medical histories such as history of chronic lung disease,history of heart cerebrovascular disease of severe cases,were higher than that of non-severe cases(P＜0.001).Multivariate logistic regression showed that the male,the higher age,current address in community,no vaccination,the longer interval time between onset and visit,fever,difficulty in breathing/shortness of breath,the history of chronic lung disease,the history of heart cerebrovascular disease raised the risk of becoming severe cases.The healing time for severe cases was longer than that for non-severe cases(P＜0.001).Conclusion Sex,age,current address,vaccination,interval time between onset and visit,fever,difficulty in breathing/shortness of breath,history of chronic lung disease,and history of heart cerebrovascular disease are the influencing factors for severe illness.
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Objective·To evaluate the relationship between body mass index(BMI)and chronic metabolic diseases.Methods·The elderly(≥60 years old)who were underwent physical examination in the Physical Examination Center of Renji Hospital,Shanghai Jiao Tong University School of Medicine from 2014 to 2021 were studied.Their results of biochemical indicators were collected.Their height,body weight,and blood pressure were measured by trained nurses.The history of chronic metabolic diseases was collected by self-reported questionnaire.Systolic blood pressure≥140 mmHg(1 mmHg=0.133 kPa),diastolic blood pressure≥90 mmHg,or self-reported hypertension history was defined as hypertension.Fasting blood glucose≥7.0 mmol/L or self-reported history of diabetes was defined as diabetes.Total cholesterol≥6.2 mmol/L,triglyceride≥2.3 mmol/L,or self-reported history of dyslipidemia was defined as dyslipidemia.The relationship between BMI and hypertension,diabetes,and dyslipidemia was evaluated by using receiver operator characteristic(ROC)curve analysis and binary logistic regression.Results·Data of 59 083 subjects were collected[30 807 men and 28 276 women,average age:(67.9±6.3)years old].The prevalence of hypertension,diabetes and dyslipidemia was 76.5%(45 219/59 083),24.1%(14 225/59 083)and 50.0%(29 544/59 083),respectively.Compared to the elderly people aged 60?74 years,those aged 75 years and above had a higher proportion of hypertension and diabetes,and a lower proportion of dyslipidemia and no metabolic abnormalities.With ROC analysis,the BMI cut-off values for hypertension,diabetes,and dyslipidemia were 24.3,23.9,and 23.9 kg/m2.The BMI cut-off values for hypertension and diabetes in elderly men were similar to those in elderly women(for hypertension:24.3 kg/m2 in elderly men vs 24.2 kg/m2 in elderly women;for diabetes:24.0 kg/m2 in elderly men vs 23.7 kg/m2 in elderly women);however,BMI cut-off value for dyslipidemia was obviously higher in elderly men than that in elderly women(24.0 kg/m2 in elderly men vs 22.5 kg/m2 in elderly women).The BMI cut-off value for chronic metabolic diseases was higher in the elderly people aged 60?74 years than that in the elderly people aged 75 years and above(24.2?24.7 kg/m2 vs 22.9?23.8 kg/m2).Conclusion·Elderly people aged 60?74 years should maintain the BMI below 24.0 kg/m2,while those aged 75 years and above should aim for the BMI below 23.0 kg/m2,so as to reduce the risk of chronic metabolic diseases.
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【Objective】 To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE) intervention timing and liver injury periodization in patients with exertional heat stroke(EHS). 【Methods】 Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected, then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT, AST, TBIL and DBIL. According to propensity score matching analysis, 11 patients in the survival group and 12 patients in the death group were included in the statistical analysis, and 20 of them were treated with TPE. The changes in indicators and clinical outcomes before and after TPE were observed, in order to evaluate the impact of intervention timing on prognosis. 【Results】 Among the 23 patients, 14 had no liver injury or could progress to the repair phase, resulting in 3 deaths(with the mortality rate of 21.43%), while 9 patients failed to progress to the repair phase, resulting in 9 deaths(with the mortality rate of 100%), with significant differences(P<0.05). The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13), while that of intervention after reaching or exceeding the third stage was 85.71%(6/7), and the difference was statistically significant(P<0.05). 【Conclusion】 TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes, thereby improving prognosis and reducing mortality.
摘要
【Objective】 To review the occurrence of allergic reactions during therapeutic plasma exchange (TPE) and to explore the risk factors of TPE allergic reactions. 【Methods】 The clinical data of 929 patients treated with TPE using plasma components by the Department of Transfusion Medicine in our medical center from 2018 to 2023 were collected. The influencing factors of allergic reactions were analyzed by univariate analysis, and the independent risk factors of allergic reactions were analyzed by logistic multivariate regression analysis. 【Results】 A total of 4 071 TPEs were performed in 929 patients.Among them, 198 patients (21.31%) experienced 349 times (8.57%) of allergic reactions, with the incidence of grade Ⅰ, Ⅱ and Ⅲ allergic reactions of 16.33%, 81.38% and 2.29%, respectively, and no deaths. The univariate analysis showed that the patient′s age, allergy history, diagnosis of immune-related diseases, ICU admission, plasma consumption, total blood volume, maximum blood flow rate and combined use of albumin were related to the occurrence of allergic reactions (P<0.05). Multivariate regression analysis showed that young patients, a history of allergy, immune-related diseases and non-ICU patients were prone to allergic reactions in TPE, but the treatment options of TPE such as substitute fluid category, plasma consumption and blood flow rate were not related to the occurrence of allergic reactions. 【Conclusion】 There are significant individual differences in the occurrence of allergic reactions for TPE, and young age, history of allergies, immune-related diseases and non-ICU patients are risk factors for allergic reactions in TPE. Identifying patients with risk factors before TPE treatment and giving corresponding preventive measures can reduce the incidence of allergic reactions.
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Objective To explore the residual level of FPMs in indoor dust samples in Shenzhen from 2020 and 2021, and to analyze its temporal distribution characteristics. Methods In the present study, indoor dust samples (n=193) from residential buildings in Shenzhen. were collected to analyze the temporal variation characteristics of FPMs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to determine the concentrations of FP and its four major metabolites (fipronil-sulfone, fipronil-sulfide, fipronil-desulfinyl, and fipronil-amide; abbreviated as FP-SFO, FP-SFI, FP-DES, and FP-AM) in the samples. The sum of the concentrations of FP and its four metabolites was represented as additive mass concentration (ΣFPMs). Additionaly, Wilcoxon test was performed to determine the temporal distribution differences of FPMs’ concentrations. Results From 2020 to 2021, the concentration of ΣFPMs for the in door dust samples in Shenzhen ranged from 0.51 to 4 415 ng/g (median: 18.8ng/g). FP, FP-SFO AND FP-SFI were the major target analytes in the sample with detection rates of 90.60%，86.20% and 75.40%, respectively. The detection rates of other metabolites were low (≤ 44.3%). Analysis of the temporal variation trend of FPMs’ concentrations showed that there was no significant difference in the levels of ΣFPMs between warm season（spring and summer）and cold season（autumn and winter）in the indoor dust samples from 2020 to 2021(2.38 vs 2.84ng/g , P > 0.05). However , the concentrations of FP-SFI and ΣFPMs in the indoor dust samples collected from 2021 showed an significantly increasing trend compared with 2020（1.02 vs 1.89 , 17.80vs. 20.10 ng/g , P < 0.05). Conclusion From 2020 to 2021 , the detection level of FPMs in indoor dust in Shenzhen is relatively high and shows an upward trend , with no obvious seasonal difference. However, whether the residual level of FPMs in indoor dust poses a risk to human health needs further study.
摘要
Objective: To propose a new staging system for presacral recurrence of rectal cancer and explore the factors influencing radical resection of such recurrences based on this staging system. Methods: In this retrospective observational study, clinical data of 51 patients with presacral recurrence of rectal cancer who had undergone surgical treatment in the Department of Gastrointestinal Surgery, Peking University People's Hospital between January 2008 and September 2022 were collected. Inclusion criteria were as follows: (1) primary rectal cancer without distant metastasis that had been radically resected; (2) pre-sacral recurrence of rectal cancer confirmed by multi-disciplinary team assessment based on CT, MRI, positron emission tomography, physical examination, surgical exploration, and pathological examination of biopsy tissue in some cases; and (3) complete inpatient, outpatient and follow-up data. The patients were allocated to radical resection and non-radical resection groups according to postoperative pathological findings. The study included: (1) classification of pre-sacral recurrence of rectal cancer according to its anatomical characteristics as follows: Type I: no involvement of the sacrum; Type II: involvement of the low sacrum, but no other sites; Type III: involvement of the high sacrum, but no other sites; and Type IV: involvement of the sacrum and other sites. (2) Assessment of postoperative presacral recurrence, overall survival from surgery to recurrence, and duration of disease-free survival. (3) Analysis of factors affecting radical resection of pre-sacral recurrence of rectal cancer. Non-normally distributed measures are expressed as median (range). The Mann-Whitney U test was used for comparison between groups. Results: The median follow-up was 25 (2-96) months with a 100% follow-up rate. The rate of metachronic distant metastasis was significantly lower in the radical resection than in the non-radical resection group (24.1% [7/29] vs. 54.5% [12/22], χ2=8.333, P=0.026). Postoperative disease-free survival was longer in the radical resection group (32.7 months [3.0-63.0] vs. 16.1 [1.0-41.0], Z=8.907, P=0.005). Overall survival was longer in the radical resection group (39.2 [3.0-66.0] months vs. 28.1 [1.0-52.0] months, Z=1.042, P=0.354). According to univariate analysis, age, sex, distance between the tumor and anal verge, primary tumor pT stage, and primary tumor grading were not associated with achieving R0 resection of presacral recurrences of rectal cancer (all P>0.05), whereas primary tumor pN stage, anatomic staging of presacral recurrence, and procedure for managing presacral recurrence were associated with rate of R0 resection (all P<0.05). According to multifactorial analysis, the pathological stage of the primary tumor pN1-2 (OR=3.506, 95% CI: 1.089-11.291, P=0.035), type of procedure (transabdominal resection: OR=29.250, 95% CI: 2.789 - 306.811, P=0.005; combined abdominal perineal resection: OR=26.000, 95% CI: 2.219-304.702, P=0.009), and anatomical stage of presacral recurrence (Type III: OR=16.000, 95% CI: 1.542 - 166.305, P = 0.020; type IV: OR= 36.667, 95% CI: 3.261 - 412.258, P = 0.004) were all independent risk factors for achieving radical resection of anterior sacral recurrence after rectal cancer surgery. Conclusion: Stage of presacral recurrences of rectal cancer is an independent predictor of achieving R0 resection. It is possible to predict whether radical resection can be achieved on the basis of the patient's medical history.
Subject(s)
Humans , Neoplasm Recurrence, Local/diagnosis , Rectal Neoplasms/therapy , Retrospective Studies , Pelvis/pathology , Recurrence , Treatment Outcome摘要
Objective: In this study, we aimed to investigate the prevalence of low anterior resection syndrome (LARS) in patients who had survived for more than 5 years after sphincter-preserving surgery for rectal cancer and to analyze its relationship with postoperative time. Methods: This was a single-center, retrospective, cross-sectional study. The study cohort comprised patients who had survived for at least 5 years (60 months) after undergoing sphincter- preserving radical resection of pathologically diagnosed rectal adenocarcinoma within 15 cm of the anal verge in the Department of Gastrointestinal Surgery, Peking University People's Hospital from January 2005 to May 2016. Patients who had undergone local resection, had permanent stomas, recurrent intestinal infection, local recurrence, history of previous anorectal surgery, or long- term preoperative defecation disorders were excluded. A LARS questionnaire was administered by telephone interview, points being allocated for incontinence for flatus (0-7 points), incontinence for liquid stools (0-3 points), frequency of bowel movements (0-5 points), clustering of stools (0-11 points), and urgency (0-16 points). The patients were allocated to three groups based on these scores: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). The prevalence of LARS and major LARS in patients who had survived more than 5 years after surgery, correlation between postoperative time and LARS score, and whether postoperative time was a risk factor for major LARS and LARS symptoms were analyzed. Results: The median follow-up time of the 160 patients who completed the telephone interview was 97 (60-193) months; 81 (50.6%) of them had LARS, comprising 34 (21.3%) with minor LARS and 47 (29.4%) with major LARS. Spearman correlation analysis showed no significant correlation between LARS score and postoperative time (correlation coefficient α=-0.016, P=0.832). Multivariate analysis identified anastomotic height (RR=0.850, P=0.022) and radiotherapy (RR=5.760, P<0.001) as independent risk factors for major LARS; whereas the postoperative time was not a significant risk factor (RR=1.003, P=0.598). The postoperative time was also not associated with LARS score rank and frequency of bowel movements, clustering, or urgency (P>0.05). However, the rates of incontinence for flatus (3/31, P=0.003) and incontinence for liquid stools (8/31, P=0.005) were lower in patients who had survived more than 10 years after surgery. Conclusions: Patients with rectal cancer who have survived more than 5 years after sphincter-preserving surgery still have a high prevalence of LARS. We found no evidence of major LARS symptoms resolving over time.
Subject(s)
Humans , Rectal Neoplasms/pathology , Cross-Sectional Studies , Low Anterior Resection Syndrome , Postoperative Complications/etiology , Retrospective Studies , Flatulence/complications , Anal Canal/pathology , Diarrhea , Quality of Life摘要
The growth environment of medicinal plants plays an important role in the formation of their medicinal quality. However, there is a lack of combined analysis studying the close relationship between the growth environment, chemical components, and related biological activities of medicinal plants. Therefore, this study investigated the effect of different soil moisture treatments on the efficacy to eliminate dampness and relieve jaundice and the flavonoid content of Sedum sarmentosum, and explored their correlation. The flavonoid content in the decoction of S. sarmentosum growing under field conditions with soil moisture levels of 35%-40%(T1), 55%-60%(T2), 75%-80%(T3), and 95%-100%(T4) was compared. The effects of these treatments on liver function parameters, liver inflammation, and oxidative damage in mice with dampness-heat jaundice were evaluated, and the correlation between pharmacological indicators and flavonoid content was analyzed. The results showed that the total flavonoid and total phenolic acid content in the decoction of S. sarmentosum were highest in the T1 treatment, followed by the T3 treatment. The content of quercetin, kaempferol, and isorhamnetin was highest in the T2, T1, and T3 treatments, respectively. Among the different moisture treatments, the T3 group of S. sarmentosum effectively reduced the levels of serum ALT, AKP, TBIL, DBIL, TBA, as well as hepatic TNF-α and IL-6 in mice with jaundice, followed by T2 treatment, especially in reducing AST level. The T4 treatment had the poorest effect. Correlation analysis showed a significant negative correlation between AST, ALT, AKP levels in mice and the total content of quercetin and the three flavonoids. MDA showed a significant negative correlation with the total flavonoid content and kaempferol. TNF-α exhibited a significant negative correlation with the content of isorhamnetin. In conclusion, S. sarmentosum growing under field conditions with a soil moisture level of 75%-80% exhibited the best efficacy to eliminate dampness and relieve jaundice. This study provides insights for optimizing the cultivation mode of medicinal plants guided by pharmacological experiments.
Subject(s)
Mice , Animals , Flavonoids/chemistry , Plant Extracts/pharmacology , Quercetin , Sedum/chemistry , Kaempferols , Soil , Tumor Necrosis Factor-alpha , Plants, Medicinal/chemistry , Jaundice/drug therapy摘要
Objective: To understand the core knowledge level and influencing factors of chronic disease prevention and control in Adults in China, and to provide a scientific basis for formulating chronic disease prevention and control measures. Methods: In this study, cross-sectional survey and quota sampling were used to recruit 173 819 permanent residents aged 18 and above from 302 counties of adult chronic diseases and nutrition surveillance in China to conduct an online questionnaire survey, including basic information and core knowledge of chronic diseases. The scores of the core knowledge of chronic disease prevention and control were described by median and interquartile range, the Wilcoxon rank sum test or the Kruskal Wallis test was used for the inter-group comparison, and the correlation factors of the total score were analyzed by the multilinear regression model. Results: A total of 172 808 participants were surveyed in 302 counties and districts, of which 42.60%(73 623) were male and 57.40%(99 185) were female; The proportion of respondents aged 18-44, 45-59, and 60 years old and above was 54.74% (94 594), 30.91% (53 423) and 14.35% (24 791), respectively. The total score of the core knowledge of chronic prevention and control in the total population was 66(13), and the scores of different characteristic groups were different, and the differences were statistically significant: the eastern region had the highest score at 67(11) (H=840.66, P<0.01), the urban 66(12) was higher than the rural 65(14) (Z=-31.35, P<0.01), and the male 66(14) was lower than female 66(12) (Z=-11.66, P<0.01), 18-24 years old 64(13) was lower than other age groups(H=115.80, P<0.01), and undergraduate degree and above had the highest score compared to other academic qualifications, with 68(9) points(H=2 547.25, P<0.01). Multivariate analysis showed that eastern (t=27.42, P<0.01), central (t=17.33, P<0.01), urban (t=5.69, P<0.01), female (t=17.81, P<0.01), high age (t=46.04, P<0.01) and high education (t=57.77, P<0.01) had higher scores of core knowledge of chronic disease prevention and control than other groups, the scores of core knowledge of chronic disease prevention and control of professional and technical personnel (t=8.63, P<0.01), state enterprises and institutions (t=38.67, P<0.01), agriculture, forestry, animal husbandry, fishery and water conservancy production (t=5.30, P<0.01), production, transportation and commercial personnel (t=24.87, P<0.01), and other workers (t=8.89, P<0.01) were higher than those of non-employed people. Conclusion: There are differences in the total scores of the core knowledge of chronic disease prevention and control in different characteristics of people in China, and in the future, health education on the prevention and treatment of chronic diseases should be strengthened for specific groups to improve the knowledge level of residents.
Subject(s)
Female , Humans , Male , China/epidemiology , Chronic Disease , Cross-Sectional Studies , East Asian People , Occupations , Surveys and Questionnaires , Health Knowledge, Attitudes, Practice摘要
Objective To explore the protective mechanism of transdifferentiation of glomerular endothelial cells based on the differentiated embryonic chondrocyte gene 2 (DEC2) via the TGF-β/ROCK1 signaling pathway. Methods The 24 mice were randomly divided into sham group, UUO group, UUO combined with vector group and UUO combined with DEC2 group, with 6 mice in each group. A unilateral ureteral obstruction (UUO) model was established in each group, except for the sham group. In the UUO combined with vector group and UUO combined with DEC2 group, 10 μL (108 PFU) of vector or DEC2 was injected into each kidney on day 0 (immediately after UUO) under the guidance of the ultrasound system. The mice were sacrificed 14 days after the operation, and the kidneys were collected for histological examination and Western blot analysis: HE staining was used to observe the histological changes of kidneys, Masson staining to observe the renal fibrosis, and Western blot analysis to detect the protein expression. In vitro, normal human glomerular endothelial cells (GEnCs) was selected as the research objects. GEnCs stimulated with TGF-β were treated with ROCK1 inhibitor Y-27632 or DEC2 transfection. Western blot analysis was used to detect the expression of ROCK1, α-SMA, DEC2 and E-cadherin in GEnC exposed to transforming growth factor β (TGF-β). The localization of ROCK1 and DEC2 in GEnCs cells was detected by immunofluorescence cytochemistry. The relationship between the ROCK1 and DEC2 was confirmed by co-immunoprecipitation. Results Compared with the sham group, the UUO groups showed significant renal fibrosis and collagen accumulation on the 14th day. In the UUO groups, the expression of DEC2 and E-cadherin in the kidney tissue of the mice was significantly reduced, and the expression of α-SMA significantly increased. Compared with the UUO combined with vector group, the kidney fibrosis and collagen accumulation in the UUO combined with DEC2 group decreased, and the expression of ROCK1 and α-SMA decreased and the expression of DEC2 and E-cadherin increased in the kidney tissue. TGF-β enhanced the expression of ROCK1 and α-SMA in GEnCs cells in a time-dependent manner, and the levels of DEC2 and E-cadherin decreased. Treatment with the ROCK1 inhibitor Y-27632 partially abrogated the TGF-β-induced increase in the expression of ROCK1 and α-SMA and decrease in the expression of DEC2 and E-cadherin. In addition, transfection of GEnCs cells with DEC2 before TGF-β stimulation reduced the expression of ROCK1 and α-SMA, and increased the expression of DEC2 and E-cadherin. Immunofluorescence cytochemical staining showed that DEC2 co-localized with ROCK1 in GEnCs, and the co-immunoprecipitation showed that DEC2 and ROCK1 pulled down each other. Conclusions DEC2 is down-regulated in fibrotic renal tissue, while up-regulated DEC2 inhibits epithelial myofibroblast transdifferentiation and renal fibrosis of GEnC by blocking TGF-β/ROCK1 signaling pathway.
Subject(s)
Humans , Animals , Mice , Cell Transdifferentiation , Chondrocytes , Endothelial Cells , Cadherins , Signal Transduction , rho-Associated Kinases摘要
BACKGROUND@#The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).@*METHODS@#A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.@*RESULTS@#A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).@*CONCLUSIONS@#Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.
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AIM: To investigate the mechanism of pyrrolidine dithiocarbamate(PDTC)on transforming growth factor-beta 2(TGF-β2)-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells(LECs).METHODS: LECs were treated with various doses of PDTC chemicals following TGF-β2 caused EMT on these cells. Cell proliferation and lateral migration were discovered using the CCK-8 and cell scratch test. The markers of EMT, including E-cadherin, α-SMA and nuclear factor-κB(NF-κB)signaling pathway-related expression, were tested by Western Blot as well as the changes in the expression of the apoptosis-related proteins BAX, BCL-2, Caspase-3, and Cyclin D1.RESULTS: The proliferation and migration viability of cells in the TGF-β2 treated group was increased compared to the group without TGF-β2, and the expression of α-SMA increased whereas the E-cadherin expression decreased. With the effect of TGF-β2, NF-κB p65 and phosphorylated NF-κB p65 expression increased, the concentration of TGF-β2 that had the greatest capacity for proliferation and migration was 10 ng/mL(P<0.05). Mechanism study of PDTC-induced EMT reversal and apoptosis showed that cell viability and migratory capability were both significantly reduced after PDTC intervention; PDTC prevents IκB phosphorylation, thus inhibiting NF-κB nuclear translocation. Protein associated to the NF-κB signaling pathway, and protein expression of NF-κB/IκBα/p-IκBα/Iκκ-α/p-Iκκ-α was decreased(P<0.05), PDTC increased the expression of the pro-apoptotic protein BAX/Caspase-3, expression of the inhibitor of apoptosis protein BCL-2 and the cell cycle protein Cyclin D1 was reduced. The expression of NF-κB/IκB mRNA was reduced, expression of the apoptosis-related mRNA BAX increased, while BCL-2 reduced.CONCLUSION: The EMT in LECs cells induced by TGF-β2 can be significantly reversed by PDTC, which may be related to the decreased expression of NF-κB p65/IκB/Iκκ-α and activation of apoptosis-related protein. PDTC can reverse EMT by inhibiting NF-κB signaling pathway and induce apoptosis of abnormally proliferated cells, which will provide new potential therapeutic agents for posterior capsular opacification(PCO)treatment.
摘要
OBJECTIVE@#To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests.@*METHODS@#In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years.@*RESULTS@#In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect.@*CONCLUSION@#Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.
Subject(s)
Humans , Diabetes Mellitus, Type 2/therapy , Self Efficacy , Self-Management , Blood Glucose Self-Monitoring , Blood Glucose , Self Care摘要
OBJECTIVES@#To summarize the clinical features of neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).@*METHODS@#The medical data of 23 neonates with Omicron variant of SARS-CoV-2 infection admitted to the City North Campus of Urumqi First People's Hospital from October to December 2022 were retrospectively reviewed.@*RESULTS@#All 23 infants had a history of exposure to confirmed caregivers with SARS-CoV-2 infection after birth, and none of them was vertically transmitted. Clinical classification: 5 cases of asymptomatic infection, 18 cases of mild infection, and no cases of moderate, severe, or critically ill. The first symptoms were fever in 13 cases, cough in 3 cases, nasal congestion in 1 case, and diarrhea in 1 case. Blood white blood cell counts decreased in 2 cases, and C-reactive protein increased in 1 case. Seven infants underwent chest X-ray examination due to cough or shortness of breath, and one of which showed focal exudative changes, while the rest showed no abnormal changes. All infants were discharged after symptomatic treatment and the median hospital stay was 6 days. The duration of nucleic acid positivity of SARS-CoV-2 was negatively correlated with N gene Ct values and ORF1ab gene Ct values (rs=-0.719 and -0.699, respectively; P<0.05). One month after discharge, all infants had no symptoms or signs of nucleic acid re-positivity.@*CONCLUSIONS@#The clinical manifestations are usually mild or asymptomatic in neonates infected with SARS-CoV-2 Omicron variant. The lower the Ct values of the N and ORF1ab genes of SARS-CoV-2, the longer the duration of nucleic acid positivity. Neonates infected with SARS-CoV-2 Omicron variant can have a good prognosis after symptomatic treatment.
Subject(s)
Humans , Infant, Newborn , Cough , COVID-19 , Retrospective Studies , SARS-CoV-2摘要
OBJECTIVES@#To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis.@*METHODS@#Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase.@*RESULTS@#The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05).@*CONCLUSIONS@#Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.
Subject(s)
Animals , Mice , HMGB1 Protein , Melatonin/therapeutic use , Mice, Inbred C57BL , NF-kappa B , NLR Family, Pyrin Domain-Containing 3 Protein , Oxygen/adverse effects , Peroxidase , Receptors, Melatonin , Retinal Diseases/drug therapy摘要
Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.