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ObjectiveTo explore the influence of excessive weight gain during pregnancy in pre-pregnancy overweight and obese women on pregnancy outcomes and neonatal conditions， and to provide scientific evidence for formulating weight management strategies before and during pregnancy and prevent adverse pregnancy outcomes. MethodsClinical data of 2 172 parturients collected from a community in Huangpu District from 2017 to 2021 were retrospectively analyzed， and they were divided into pre-pregnancy overweight and obesity group （n=530）， normal pre-pregnancy weight group（n=937）， and underweight pre-pregnancy group（n=705） according to maternal precursor body mass index （BMI）. Based on their weight gain during pregnancy，the parturient were divided into moderate gestational weight gain （MGWG） group and excessive gestational weight gain （EGWG） group. Meanwhile， the pregnancy and neonatal outcomes such as postpartum hemorrhage， puerperal infection， placental abruption， premature rupture of membranes， mode of delivery， premature birth， stillbirth， fetal distress， admission to the intensive care unit （ICU）， macrosomia， and Apgar score， were recorded. Then the differences in pregnancy and neonatal outcomes between groups were compared. The effects of pre-pregnancy BMI and gestational weight gain on pregnancy outcomes and neonatal conditions was retrospectively analyzed. ResultsThe pre-pregnancy overweight and obese group had higher proportions of placental abruption， premature rupture of membranes， cesarean section， premature birth， fetal distress， and macrosomia compared to the normal pre-pregnancy weight group and the underweight pre-pregnancy group， with Apgar scores lower than the normal pre-pregnancy weight group and the underweight pre-pregnancy group （all P<0.05）. The EGWG group had higher proportions of postpartum hemorrhage， placental abruption， premature rupture of membranes， cesarean section， premature birth， fetal distress， admission to the ICU， and macrosomia than the MGWG group （all P<0.05）. In the pre-pregnancy overweight and obese group， the EGWG group had higher proportions of placental abruption， premature rupture of membranes， premature birth， fetal distress， admission to the ICU， and macrosomia than the MGWG group， with lower Apgar scores than the MGWG group （all P<0.05）. In the normal pre-pregnancy weight group， the EGWG group had higher proportions of placental abruption， premature rupture of membranes， premature birth， fetal distress， admission to the ICU， and macrosomia than the MGWG group （all P<0.05）. In the pre-pregnancy overweight and obese group， the EGWG group had higher proportions of premature rupture of membranes， cesarean section， premature birth， fetal distress， and macrosomia than the EGWG group in the normal pre-pregnancy weight group（all P<0.05）. Logistic regression analysis showed that EGWG in pre-pregnancy overweight and obese women was a risk factor for placental abruption （OR=2.971， 95%CI： 1.098‒8.042）， premature rupture of membranes （OR=4.662， 95%CI： 2.798‒7.770）， cesarean delivery （OR=1.375，95%CI： 1.260‒2.541）， premature birth （OR=4.249， 95%CI： 2.384‒7.573）， fetal distress （OR=3.238， 95%CI： 1.589‒6.598）， admission to the ICU （OR=3.010， 95%CI： 1.265‒7.164）， and macrosomia （OR=5.437， 95%CI： 3.392‒8.716） （all P<0.05）. ConclusionExcessive gestational weight gain in pre-pregnancy overweight and obese women is a risk factors for placental abruption， premature rupture of membranes， cesarean section， premature birth， fetal distress， admission to the ICU， and macrosomia.
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Objective To observe the clinical efficacy of thumb-tack needling for subcutaeous embedding combined with joint mobilization in the treatment of post-stroke shoulder-hand syndrome.Methods A total of 80 patients with post-stroke shoulder-hand syndrome were randomly divided into a treatment group and a control group,with 40 patients in each group.Both groups were given arthrocentesis,the control group was given ordinary acupuncture on the basis of arthrocentesis,and the treatment group was combined with thumb-tack needling for subcutaeous embedding.One course of treatment was 4 weeks and a total of 4 weeks of treatment was given.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes of Visual Analogue Scale(VAS)of pain scores and simplified Fugl-Meyer Assessment(FMA)scores,as well as the pain-free passive forward flexion and abduction of the shoulder joint of the affected limb were observed before and after treatment.The Simple Quality of Life Scale(SF-36)scores of the patients in the two groups were compared after treatment.The safety and the occurrence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate was 95.00%(38/40)in the treatment group and 80.00%(32/40)in the control group.The efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the VAS scores and upper extremity FMA scores of the patients in the two groups were significantly improved(P＜0.05),and the treatment group was significantly superior to the control group in improving the VAS scores and upper extremity FMA scores,and the differences were statistically significant(P＜0.05).(3)After treatment,the joint mobility of patients in the two groups were significantly improved(P＜0.05),and the improvement of shoulder joint movement in the treatment group was superior to that in the control group,and the difference was statistically significant(P＜0.05).(4)After treatment,the SF-36 Quality of Life Scale scores of the treatment group were significantly superior to those of the control group in terms of physical function,psychological function,emotional health,and social function levels,and the difference was statistically significant(P＜0.05).(5)There was no significant difference in the incidence of adverse reactions between the treatment group and the control group(P＞0.05).Conclusion Thumb-tack needling for subcutaeous embedding combined with joint mobilization exert certain effect in the treatment of post-stroke shoulder-hand syndrome.It can significantly improve the pain symptoms of patients,thus improving their quality of life,and the clinical effect is remarkable.
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Objective To investigate the clinical effect of LUO's Nephropathy Recipe Ⅲ(composed of Sargassum,Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Rehmanniae Radix Praeparata,calcined Ostreae Concha,Houttuyniae Herba,Schizonepetae Spica,etc.)combined with conventional western medicine in treating stage 3-5 non-dialysis chronic kidney disease(CKD)of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type.Methods A total of 180 patients with stage 3-5 non-dialysis CKD of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type were randomly divided into observation group and control group,with 90 cases in each group.The control group was given conventional western medicine for symptomatic treatment,and the observation group was treated with LUO's Nephropathy RecipeⅢon the basis of treatment for the control group.The course of treatment for the two groups covered one month.Before and after treatment,the levels of serum inflammatory factors,renal function indicators and urine protein parameters in the two groups were observed.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After one month of treatment,the total effective rate in the observation group was 95.56%(86/90)and that in the control group was 81.11%(73/90).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the serum levels of inflammatory factors of transforming growth factor β1(TGF-β1),monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the levels of renal function indicators of blood urea nitrogen(BUN),serum creatinine(Scr),blood uric acid(UA),and cystatin C(Cys-C)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of 24-hour urine protein quantification and urine microalbumin in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(5)The incidence of adverse reactions in the observation group was 4.44%(4/90),which was significantly lower than that of 15.56%(14/90)in the control group,and the difference was statistically significant between the two groups(P＜0.05).Conclusion LUO's Nephropathy Recipe Ⅲ combined with conventional western medicine exerts satisfactory efficacy in treating stage 3-5 non-dialysis CKD patients with spleen-kidney deficiency with turbidity-toxin-stasis obstruction syndrome type,and the therapy can significantly alleviate the inflammatory response,improve the renal function,decrease the urinary protein excretion of the patients,with high safety profile.
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Objective To construct quality evaluation indicators for perioperative nursing in heart transplantation,and to provide standard and professional quantitative bases for monitoring and management of perioperative nursing quality.Methods This study was conducted based on the frame work of the three-dimensional"structure-process-outcome"quality model,using literature review,Delphi method and analytic hierarchy to determine the content of the indicators,and the weight of each index.Results A total of 22 experts from 14 qualified heart transplantation hospitals were included,and a total of 2 rounds of consultations were conducted.The effective recovery rates of 2 rounds of expert consultation questionnaires were 100％.The authority coefficients were 0.817.The variation coefficients of each item ranged from 0.025～0.169 and 0.039～0.157.The Kendall harmony coefficients were 0.126 and 0.225(P＜0.001).The final evaluation indicators for perioperative nursing quality in heart transplantation included 3 first-level indicators,12 second-lever indicators and 59 third-level indicators.Conclusion The evaluation indicators of perioperative nursing quality in heart transplantation was scientific,comprehensive and specialized,which can provide references for the evaluation of perioperative nursing quality in heart transplantation.
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OBJECTIVE To evaluate the cost-effectiveness of apatinib combined with adriamycin in the second-line chemotherapy of platinum-resistant recurrent ovarian cancer （OC） from the perspective of the health system in China. METHODS A three-state partitioned survival model was constructed based on the APPROVE clinical trial and related literature data， with a model simulation time frame of 10 years and a 4-week cycle， and both cost and utility values were discounted using a 5% discount rate. Cost and quality-adjusted life years （QALYs） were used as a model output indicator and the incremental cost-effectiveness ratio （ICER） was calculated to evaluate the cost-effectiveness of apatinib combined with adriamycin versus adriamycin chemotherapy in the second-line treatment of platinum-resistant recurrent OC. One-way sensitivity analysis， probability sensitivity analysis and scenario analysis were used to verify the robustness of the base-case analysis results. RESULTS The results of base-case analysis indicated that compared with chemotherapy alone， ICER of patients receiving apatinib combined with adriamycin was 124 678.25 yuan/QALY， which was less than willingness-to-pay （WTP） threshold set in this study [3 times per capita gross domestic product （GDP） of China in 2022 （257 094 yuan）]. The results of scenario analysis showed that， with the extension of the simulation time limit， the ICER of apatinib combined with adriamycin was gradually reduced， and the decline was gradually reduced， but both were less than WTP threshold. The results of single factor sensitivity analysis showed that the factors that had the greatest impact on ICER were the utility value of progression， body surface area， discount rate，and the cost of best supportive treatment， etc. The results of probability sensitivity analysis showed that under WTP threshold set in this study， the economic probability of apatinib combined with adriamycin was about 99%. CONCLUSIONS From the perspective of China’s health system， using three times the per capita GDP in 2022 as the WTP threshold， the combination of apatinib and adriamycin is more cost-effective than adriamycin alone in second-line chemotherapy for platinum-resistant recurrent OC.
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Objective To evaluate the cost-effectiveness of edaravone dexborneol versus edaravone alone combined with conventional therapy in patients with acute ischemic stroke(AIS).Methods From the perspective of the healthcare systems,a decision tree model was constructed using the data from the randomized double-blind comparative trial of edaravone dexborneol in the treatment of acute ischemic stroke(TASTE trial).Cost-utility analysis was used to evaluate the health benefits of edaravone dexborneol at 1 month and 5 years.The robustness of the results was tested by single factor sensitivity analysis and probability sensitivity analysis.Results For AIS patients,the 1-month incremental cost-utility ratio was 53 212.89 yuan/quality-adjusted life-year(QALY),and the 5-year incremental cost-utility ratio was 49 631.25 yuan/QALY,both of which were smaller than China's per capita GDP in 2022(85 698 yuan).Univariate sensitivity analysis showed that the change of NIHSS score in 2 groups of improved patients,the probability of improvement in 2 groups and the probability of deterioration in edaravone group were the most influential factors on the outcome of incremental cost effectiveness.The results of probabilistic sensitivity analysis showed that edaravone dexcborneol was more economical when WTP was 1 times China's per capita GDP in 2022.Conclusion Edaravon dexborneol is a more effective and economical treatment for acute ischemic stroke patients than edaravone alone.
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Objective:To explore the application effect of the modified sandwich teaching method based on constructivism theory in clinical teaching of neurology nursing interns.Methods:A total of 29 nursing interns who practiced in the Department of Neurology of the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from June 2020 to May 2021 were selected as the control group, using the conventional clinical nursing teaching method, and 28 nursing interns who practiced from June 2021 to May 2022 were selected as the observation group, using the modified sandwich teaching method based on constructivism theory. Before graduating from the Department of Neurology, nursing interns in the two groups were compared in terms of the teaching effects, such as the score of learning initiative, theoretical examination, operation examination, and nursing round report. SPSS 25.0 was used for t test and chi-square test. Results:The score for each dimension (learning driving force, learning objectives, in-depth learning, controlled learning, and solid learning) and total score in the observation group were significantly higher than those in the control group ( P<0.05). There was no significant difference between the two groups in the scores of theoretical examination and operation examination (89.11±3.58 vs. 88.97±2.74, 93.79±2.48 vs. 93.86±2.20; P>0.05); the scores of nursing rounds in the observation group were significantly higher than those in the control group (88.61±2.60 vs. 83.38±3.97, P<0.05). Conclusions:The modified sandwich teaching method based on constructivism theory can enhance the learning initiative and comprehensive analysis ability of nursing interns in the Department of Neurology. It is suitable for clinical nursing teaching in the Department of Neurology and is worth popularizing.
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OBJECTIVE To investigate the effect of icariin(ICA)on the ubiquitination modification of β-amy-loid precursor protein(APP)in Alzheimer's disease mice.METHODS In vitro,① HEK 293 cells stably overex-pressing human APP695(OE-hAPP)were treated with different concentrations of ICA(10-100 μmol·L-1)for 24 h and the cell viability was detected by MTT assay.②CHX(50 mg·L-1)was used to block protein synthesis and MG132(20 μmol·L-1)inhibits proteasome activity,then the level of APP in different time(0,0.5,1,2,3 and 4 h)and the ubiquitination were tested by Western blotting.③ E3 ubiquitin ligases HMG-CoA reductase degradation pro-tein 1(HRD1)protein expression in OE-hAPP was tested by Western blotting,as well as the level and ubiquitination of APP were tested under HRD1 silent condition by Co-IP and Western blotting.In vivo,① male APP/PS1 mice and wild type(WT)mice were randomly divided into 5 groups:WT,WT+ICA,APP/PS1,APP/PS1+ICA,and APP/PS1+donepezil(DPZ)groups.ICA(60 mg·kg-1·d-1)and DPZ(1 mg·kg-1·d-1)were treated for 3 months by gavage from 6 months of age,and WT mice were given equal volume of distilled water.②Morris water maze and Y-maze experiments were used to detect the alteration of spatial learning memory function.③ After then,the brain tissues were collected,total proteins were extracted,APP antibodies were subjected to Co-IP,and total ubiqui-tination(Ub),K48-linked polyubiquitination(UbK48)and K63-linked polyubiquitination of APP level,APP and HRD1 proteins were detected by Western blotting.RESULTS In vitro results showed that ICA significantly enhanced APP degradation(vs control,P＜0.01),up-reg-ulated HRD1 expression(vs control,P＜0.05;vs OE-hAPP,P＜0.05),elevated the level Ub and UbK48 of APP,as well as increased APP degradation.Moreover,silenced HRD1 gene abolished abovementioned effects of ICA(vs control-siRNA,P＜0.05;vs HRD1-siRNA,P＜0.05).In vivo results showed that ICA improved the spa-tial learning and memory function APP/PS1 mice by Mor-ris water maze and Y-maze tests,increased HRD1 expres-sion(vs APP/PS1 + vehicle,P＜0.05),enhanced APP ubiquitination and reduced APP protein level(vs APP/PS1 + vehicle,P＜0.01).CONCLUSION ICA promotes the ubiquitination and proteasome-dependent degrada-tion of APP by up-regulating HRD1,thereby improving the spatial learning and memory function of Alzheimer disease mice.
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Objective To investigate the expression and role of the Sonic Hedgehog (Shh) signaling pathway in intestinal mucosal barrier injury in rats with severe acute pancreatitis (SAP). Methods A total of 48 Sprague-Dawley rats were divided into sham-operation group (Sham group), SAP model group (SAP group), SAP+Shh signaling pathway-specific agonist purmorphamine group (PUR+SAP group), and SAP+Shh signaling pathway-specific antagonist cyclopamine group (CYC+SAP group) using a random number table, with 12 rats in each group, and each group was further divided into 12-hour and 24-hour subgroups, with 6 rats in each subgroup. Rats were given retrograde injection of 5% sodium taurocholate into the pancreatic and bile ducts to establish a model of SAP, and rats in the intervention groups were given intraperitoneal injection of 0.69 mg/kg purmorphamine and 0.69 mg/kg cyclopamine before modeling. Related samples were collected at 12 and 24 hours after modeling. HE staining was used to observe the pathological changes of the pancreas and the ileum; ELISA was used to measure the serum levels of amylase, lipase, diamine oxidase (DAO), and endotoxin-core antibody (EndoCAb); the TUNEL method was used to observe the apoptosis of intestinal epithelial cells; Western blot was used to measure the expression levels of Shh, Ptch1, and Gli1 in ileal tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. Results Compared with the Sham group, the SAP group had significant increases in the pathological scores of pancreatic and ileum tissue, the serum levels of lipase, amylase, DAO, and EndoCAb, the apoptosis of intestinal epithelial cells, and the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Compared with the SAP group, the PUR+SAP group had significantly alleviated pathological injury and dysfunction of the pancreas and intestine, a significant reduction in the apoptosis of intestinal epithelial cells, and significant increases in the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Compared with the SAP group, the CYC+SAP group had significant aggravation of the pathological injury and dysfunction of the pancreas and intestine, a significant increase in the apoptosis of intestinal epithelial cells, and significant reductions in the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Conclusion The Shh signaling pathway may be involved in intestinal mucosal barrier injury in SAP and exerts a protective effect.
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Objective To analyze the epidemiological characteristics of initial acute cerebral infarction (ACI) and its correlation with meteorological factors, and to provide theoretical basis for the prevention and treatment of ACI. Methods Atotal of 308 ACI patients admitted to our hospital from 2019 to 2020 were retrospectively analyzed, and the age, gender, height, weight, complications, onset season and initial symptoms of all patients were systematically analyzed from the hospital case system. Collected during the same period of meteorological data, including: monthly average temperature (℃), monthly mean minimum temperature (℃), monthly average highest temperature (℃), monthly average diurnal range (℃), the average daily air pressure (kPa), etc., by using circular distribution analysis the season of incipient ACI onset regularity, the linear correlation analysis and multiple stepwise regression analysis of the relationship between meteorological factors and the incipient ACI onset. Results The male to female ratio of 308 patients was 1.15:1. A among of 55.84% of the patients were 65 years old or older and mainly lived in urban areas (77.27%). The main risk factors were hypertension (24.03%), followed by hyperlipidemia (24.03%). The incidence was mainly in winter (30.84%) and spring (26.62%). The first symptoms are headache, dizziness, unclear speech, followed by malignant, tinnitus, vomiting, hemiplegia, dysphagia, etc. The number of ACI cases was highest in January and December, and lowest in May and June.Linear correlation analysis showed that the number of ACI cases was negatively correlated with monthly mean air temperature, monthly mean minimum air temperature and monthly mean daily range ( r=-0.362 , -0.429, -0.374, P<0.05), and positively correlated with monthly mean air pressure ( r=0.317, P<0.05). The meteorological factors that affected the incidence of ACI were monthly mean minimum temperature, followed by monthly mean daily range (P<0.05). Conclusion Meteorological factors are the influencing factors of the incidence of initial ACI. The incidence of initial ACI is high under low temperature and high atmospheric pressure. Active intervention should be given to reduce the incidence.
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OBJECTIVE To promote the standardization and integrity of the informed consent form for clinical trials of registered anti-tumor drugs， and to protect the legitimate rights and interests of the subjects. METHODS The ethical review resolutions of clinical trial projects of registered anti-tumor drugs that were initially reviewed by the Ethics Committee of our hospital from July 1st， 2020 to July 1st， 2022 were summarized to statistically analyze the problematic items according to the “Quality Analysis Form of Informed Consent” prepared by our hospital. RESULTS Of the 316 clinical trials of registered anti- tumor drugs that were initially reviewed， 257 （81.3%） had problems with the contents of informed consent form， mainly domestic multi-center trials and phase Ⅲ trials. The main problems included the vague notification of the test fee bearer （68.5%）， the incomplete notification of the test content （59.1%）， the insufficient notification of rights and interests and risks （58.4%）， the insufficient notification of personal information protection （56.0%）， and the nonstandard expression of the informed consent form （52.5%）. CONCLUSIONS There is still a gap between the informed consent form of the clinical trials of registered anti-tumor drugs in our hospital and the requirements of the new version of Good Clinical Practice for Drugs （GCP）. The parties involved in the test can take a number of measures to improve the standardization and integrity of the informed consent form， and the research team should design the informed consent form in strict accordance with the requirements of the new GCP and pay attention to the comprehensive notification about the test. The Ethics Committee can provide the sponsor and researcher with the template of informed consent form and the key points of writing， continue to strengthen the examination ability， improve the examination quality， and effectively protect the safety and interests of the subjects.
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In recent years, with the continuous improvement of high-dose combined chemotherapy and deeper understanding of risk factors, the remission rate of childhood acute lymphoblastic leukemia has been gradually improved, but the prognosis of relapsed/refractory acute lymphoblastic leukemia(r/r ALL)is still not optimistic.Hematopoietic stem cell transplantation has become an alternative treatment for these children.With the development of cellular immunotherapy, the prognosis of children with r/r ALL is expected to be improved.Blinatumomab, as a bispecific antibody, is the first cloned antibody to be tested in clinical trials and approved by FDA for Philadelphia chromosome negative(Ph-) r/r ALL.Blinatumomab as a new generation of monoclonal antibody can significantly improve the survival of children with r/r ALL.This article focuses on the mechanism of action, drug resistance, clinical research progress and adverse reactions of Blinatumomab.
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Objective:To investigate the efficacy and adverse reactions of ticagrelor combined with atorvastatin in the treatment of acute cerebral infarction (ACI).Methods:A total of 80 patients with ACI who were diagnosed and treated in Anhui Suixi County Hospital from October 2021 to October 2022 were selected retrospectively and randomly divided into the control group and observation group, each group with 40 cases. The patients in the control group were treated with routine basic treatment and atorvastatin for ACI. The patients in the observation group was treated with ticagrelor on the basis of the control group. The clinical efficacy, neurological function, daily living ability, platelet function (platelet count, platelet inhibition rate), inflammatory factors including high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and adverse reactions of the two groups were compared.Results:The total effective rate of the observation group was higher than that of the control group: 92.50%(37/40) vs. 72.50% (29/40), there was statistical differences ( P<0.05). After treatment, the score of National Institute of Health Stroke Scale of the observation group was lower than that of the control group: (9.37 ± 2.91) points vs. (14.20 ± 3.39) points, and the score of Barthel index scale (BI) was higher than that of the control group: (72.26 ± 13.27) points vs. (58.93 ± 9.43) points, there were statistical differences ( P<0.05). After treatment, the platelet count and platelet adenosine diphosphate (ADP) inhibition rate of the observation group were higher than those of the control group: (284.65 ± 41.58) × 10 9/L vs. (210.46 ± 36.12) × 10 9/L, (79.43 ± 16.42)% vs. (62.40 ± 13.95)%, there were statistical differences ( P<0.05). After treatment, the serum hs-CRP and IL-6 levels of the observation group were lower than those of the control group: (11.64 ± 2.96) mg/L vs. (19.75 ± 4.57) mg/L, (4.26 ± 0.93) ng/L vs. (8.95 ± 1.83) ng/L, there were statistical differences ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups after treatment ( P>0.05). Conclusions:Ticagrelor combined with atorvastatin has a better therapeutic effect on ACI, which can effectively improve the neurological deficit and the ability of self-care.
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Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.
الموضوعات
Humans , Pregnancy , Female , Hypertension, Pregnancy-Induced/diagnosis , Retrospective Studies , Pre-Eclampsia/epidemiology , Risk Factors , Incidenceالملخص
Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.
الموضوعات
Adolescent , Child , Female , Humans , Male , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chromosomal Proteins, Non-Histone/genetics , Cladribine/therapeutic use , Cytarabine/therapeutic use , Daunorubicin/therapeutic use , Etoposide/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Homoharringtonine/therapeutic use , Idarubicin/therapeutic use , Leukemia, Myeloid, Acute/genetics , Oncogene Proteins/genetics , Poly-ADP-Ribose Binding Proteins/genetics , Remission Induction , Retrospective Studiesالملخص
Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.
الموضوعات
Humans , Pyroptosis , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Gasdermins , Chemoradiotherapy/adverse effects , Rectal Neoplasms/surgery , Caspases/metabolism , Diarrhea/chemically induced , Leukopenia/genetics , Genetic Variation , Dermatitisالملخص
This study aims to explore the chemical composition of Rehmanniae Radix braised with mild fire and compare the effect of processing method on the chemical composition of Rehmanniae Radix. To be specific, ultra-high performance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to screen the chemical constituents of Rehmanniae Radix. The chemical constituents were identified based on the relative molecular weight and fragment ions, literature information, and Human Metabolome Database(HMDB). The ion peak area ratio of each component before and after processing was used as the index for the variation. SIMCA was employed to establish principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) models of different processed products. According to the PCA plot, OPLS-DA plot, and VIP value, the differential components before and after the processing were screened out. The changes of the content of differential components with the processing method were analyzed. A total of 66 chemical components were identified: 57 of raw Rehmanniae Radix, 55 of steamed Rehmanniae Radix, 55 of wine-stewed Rehmanniae Radix, 51 of repeatedly steamed and sundried Rehmanniae Radix Praeparata, 62 of traditional bran-braised Rehmanniae Radix, and 63 of electric pot-braised Rehmanniae Radix. Among them, the 9 flavonoids of braised Rehmanniae Radix were from Citri Reticulatae Pericarpium. PCA suggested significant differences in the chemical composition of Rehmanniae Radix Praeparata prepared with different processing methods. OPLS-DA screened out 32 chemical components with VIP value >1 as the main differential components. Among the differential components, 9 were unique to braised Rehmanniae Radix(traditional bran-braised, electric pot-braised) and the degradation rate of the rest in braised(traditional bran-braised, electric pot-braised) or repeatedly steamed and sundried Rehmanniae Radix was higher than that in the steamed or wine-stewed products. The results indicated the chemical species and component content of Rehmanniae Radix changed significantly after the processing. The 32 components, such as rehmapicrogenin, martynoside, jionoside D, aeginetic acid, hesperidin, and naringin, were the most important compounds to distinguish different processed products of Rehmanniae Radix. The flavonoids introduced by Citri Reticulatae Pericarpium as excipient may be the important material basis for the effectiveness of braised Rehmanniae Radix compared with other processed products.
الموضوعات
Humans , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Plant Extracts/chemistry , Rehmannia/chemistry , Flavonoids/analysisالملخص
It is a basic prerequisite for the successful completion of endodontic treatment to thoroughly understand the root canal space anatomy. With the development of dental devices in dentistry, the root canal morphology of the mandibular first premolars can be presented in more detail. Before conducting root canal therapy on the mandibular first premolar with complex root canal morphology, it should be necessary to evaluate the potential difficulties and risks for making an appropriate treatment plan. The present paper reviews the research progress on the diversities of root canal morphology in mandibular first premolars in recent years, and then makes technologic recommendations based on the morphology diversities.
الموضوعات
Humans , Dental Pulp Cavity/diagnostic imaging , Bicuspid/anatomy & histology , Mandible , Tooth Root/anatomy & histology , Root Canal Therapyالملخص
Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.
الملخص
Objective: To investigate the effects and mechanism of interleukin-4-modified gold nanoparticle (IL-4-AuNP) on the wound healing of full-thickness skin defects in diabetic mice. Methods: Experimental research methods were adopted. Gold nanoparticle (AuNP) and IL-4-AuNP were synthesized by improving the methods described in published literature. The morphology of those two particles were photographed by transmission electron microscopy, and their particle sizes were calculated. The surface potential and hydration particle size of the two particles were detected by nanoparticle potentiometer and particle size analyzer, respectively. The clearance rate of IL-4-AuNP to hydrogen peroxide and superoxide anion was measured by hydrogen peroxide and superoxide anion kits, respectively. Mouse fibroblast line 3T3 cells were used and divided into the following groups by the random number table (the same below): blank control group, hydrogen peroxide alone group treated with hydrogen peroxide only, hydrogen peroxide+IL-4-AuNP group treated with IL-4-AuNP for 0.5 h and then treated with hydrogen peroxide. After 24 h of culture, the reactive oxygen species (ROS) levels of cells were detected by immunofluorescence method; cell count kit 8 was used to detect relative cell survival rate. The macrophage Raw264.7 mouse cells were then used and divided into blank control group and IL-4-AuNP group that treated with IL-4-AuNP. After 24 h of culture, the expression of arginase 1 (Arg-1) in cells was observed by immunofluorescence method. Twelve male BALB/c mice (mouse age, sex, and strain, the same below) aged 8 to 10 weeks were divided into IL-4-AuNP group and blank control group, treated accordingly. On the 16th day of treatment, whole blood samples were collected from mice for analysis of white blood cell count (WBC), red blood cell count (RBC), hemoglobin level, or platelet count and the level of aspartate aminotransferase (AST), alanine transaminase (ALT), urea, or creatinine. The inflammation, bleeding, or necrosis in the heart, liver, spleen, lung, and kidney tissue of mice were detected by hematoxylin-eosin (HE). Another 36 mice were selected to make diabetic model, and the full-thickness skin defect wounds were made on the back of these mice. The wounds were divided into blank control group, AuNP alone group, and IL-4-AuNP group, with 12 mice in each group, and treated accordingly. On the 0 (immediately), 4th, 9th, and 15th day of treatment, the wound condition was observed and the wound area was calculated. On the 9th day of treatment, HE staining was used to detect the length of neonatal epithelium and the thickness of granulation tissue in the wound. On the 15th day of treatment, immunofluorescence method was used to detect ROS level and the number of Arg-1 positive cells in the wound tissue. The number of samples was 6 in all cases. Data were statistically analyzed with independent sample t test, corrected t test, Tukey test, or Dunnett T3 test. Results: The size of prepared AuNP and IL-4-AuNP were uniform. The particle size, surface potential, and hydration particle size of AuNP and IL-4-AuNP were (13.0±2.1) and (13.9±2.5) nm, (-45.8±3.2) and (-20.3±2.2) mV, (14±3) and (16±4) nm, respectively. For IL-4-AuNP, the clearance rate to hydrogen peroxide and superoxide anion were (69±4)% and (52±5)%, respectively. After 24 h of culture, the ROS level of 3T3 in hydrogen peroxide alone group was significantly higher than that in blank control group (q=26.12, P<0.05); the ROS level of hydrogen peroxide+IL-4-AuNP group was significantly lower than that in hydrogen peroxide alone group (q=25.12, P<0.05) and close to that in blank control group (P>0.05). After 24 h of culture, the relative survival rate of 3T3 cells in hydrogen peroxide+IL-4-AuNP group was significantly higher than that in hydrogen peroxide alone group (t=51.44, P<0.05). After 24 h of culture, Arg-1 expression of Raw264.7 cells in IL-4-AuNP group was significantly higher than that in blank control group (t'=8.83, P<0.05).On the 16th day of treatment, there were no significant statistically differences in WBC, RBC, hemoglobin level, or platelet count and the level of AST, ALT, urea, or creatinine of mice between blank control group and IL-4-AuNP group (P>0.05). No obvious inflammation, bleeding or necrosis was observed in the heart, liver, spleen, lung, and kidney of important organs in IL-4-AuNP group, and no significant changes were observed compared with blank control group. On the 0 and 4th day of treatment, the wound area of diabetic mice in blank control group, AuNP alone group, and IL-4-AuNP group had no significant difference (P>0.05). On the 9th day of treatment, the wound areas both in AuNP alone group and IL-4-AuNP group were significantly smaller than that in blank control group (with q values of 9.45 and 14.87, respectively, P<0.05), the wound area in IL-4-AuNP group was significantly smaller than that in AuNP alone group (q=5.42, P<0.05). On the 15th day of treatment, the wound areas both in AuNP alone group and IL-4-AuNP group were significantly smaller than that in blank control group (with q values of 4.84 and 20.64, respectively, P<0.05), the wound area in IL-4-AuNP group was significantly smaller than that in AuNP alone group (q=15.80, P<0.05); moreover, inflammations such as redness and swelling were significantly reduced in IL-4-AuNP group compared with the other two groups. On the 9th day of treatment, compared with blank control group and AuNP alone group, the length of neonatal epithelium in the wound of diabetic mice in IL-4-AuNP group was significantly longer (all P<0.05), and the thickness of the granulation tissue in the wound was significantly increased (with q values of 11.33 and 9.65, respectively, all P<0.05). On the 15th day of treatment, compared with blank control group, ROS levels in wound tissue of diabetic mice in AuNP alone group and IL-4-AuNP group were significantly decreased (P<0.05). On the 15th day of treatment, the number of Arg-1 positive cells in the wounds of diabetic mice in IL-4-AuNP group was significantly more than that in blank control group and AuNP alone group, respectively (all P<0.05). Conclusions: IL-4-AuNP is safe in vivo, and can improve the oxidative microenvironment by removing ROS and induce macrophage polarization towards M2 phenotype, thus promote efficient diabetic wound healing and regeneration of full-thickness skin defects in diabetic mice.