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AIM:To investigate the clinical efficacy of minimally invasive foldable capsular buckle(FCB)scleral buckling in treating rhegmatogenous retinal detachment(RRD).METHOD: This retrospective study enrolled 11 patients(11 eyes)with RRD treated with minimally invasive FCB scleral buckling at the Hainan Traditional Chinese Medicine Hospital from May to July 2023. The surgeries were performed without subconjunctival anesthesia, extraocular muscle pulling, intraocular positioning, retinal cryotherapy or drainage of subretinal fluid, or FCB suture fixation. Furthermore, the best corrected visual acuity(BCVA), intraocular pressure and complications were observed.RESULTS: Minimally invasive FCB scleral buckling was performed on 11 eyes, with successful retinal reattachment in 10 eyes(91%), and the remaining 1 eye(9%)had postoperative retinal re-detachment and underwent vitrectomy with silicone oil filling for multiple retinal tears. One-time successful surgery was in 4 eyes(40%), gas injection in vitreous body after the surgery was performed in 1 eye(10%), FCB position adjustment after the surgery was performed in 3 eyes(30%), gas injection in vitreous body and FCB position adjustment after the surgery were performed in 2 eyes(20%); and FCB was removed 4-12 wk after the surgery in 5 eyes(50%), without retinal redetachment. The average BCVA(LogMAR)of the 10 eyes improved from 1.30±1.10 before surgery to 0.37±0.39 at 4 wk after surgery(P<0.01); the average preoperative intraocular pressure was 11.51±3.37 mmHg and 13.72±2.57 mmHg at 4wk after surgery(P>0.05). No serious complications occurred.CONCLUSION:Minimally invasive FCB scleral buckling effectively treats RRD with minimal injury, simple operation, time-saving, and fewer complications.
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Objective:To explore the value of fetal lung volume and mediastinal shift angle (MSA) based on fetal MRI in predicting the prognosis of congenital diaphragmatic hernia (CDH).Methods:Fetuses with left CDH that did fetal MRI in Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine from September 2016 to January 2022 were retrospectively collected. There were 65 patients, and their gestational age was 29 (26, 35) weeks when they were diagnosed with left CDH by MRI. Observed fetal lung volume and MSA were measured based on fetal MRI, and observed/expected lung volume (o/eFLV) based on gestational age was calculated. The clinical data were collected from birth to discharge, and patients were divided into survival group and death group in case of prognosis at discharge, with 54 cases in the survival group and 11 cases in the death group. The student′s t test was used to compare the difference of o/eFLV and MSA between the survival group and the death group, and the receiver operating characteristic (ROC) curve was used to evaluate the value of o/eFLV and MSA in predicting the prognosis of left CDH. Results:The o/eFLV of the survival group was 51.5%±18.3%, higher than that of the death group (27.8%±4.4%), and the difference was significant ( t=8.29, P<0.001). The MSA of the survival group was 33.1°±1.2°, lower than that of the death group (41.8°±2.7°), and the difference was significant ( t=-11.15, P<0.001). The area under the ROC curve (AUC) of o/eFLV to predict the fetal survival or death was 0.939 (95%CI 0.851-0.983), the cutoff value was 33.8%, the sensitivity was 100%, the specificity was 88.9%. The AUC of MSA was 0.998 (95%CI 0.941-1.000), the cutoff value was 37.2°, the sensitivity was 100%, the specificity was 98.2%. Conclusions:The o/eFLV and MSA that were measured based on fetal MRI can effectively predict the fetus′s prognosis with left CDH.
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Restricted and repetitive behaviors is the characteristic clinical manifestation of many neuropsychiatric diseases, which seriously affects the work, study and daily communication of patients, and brings huge mental and economic burden to the family and society.Its causes are complex and its manifestations are diverse.Current studies have shown that microglia is closely related to the occurrence of restricted and repetitive behaviors, and the in-depth study of microglia has become a research hotspot to explore the mechanism of restricted and repetitive behaviors.In recent years, studies have found that restricted and repetitive behaviors of various neuropsychiatric diseases (such as frontotemporal dementia, obsessive-compulsive disorder, autism spectrum disorder) are related to microglia.However, reliable evidence for the exact mechanism of microglia involved in restricted and repetitive behaviors remains lacking.This article reviews the recent research progress of microglia involved in restricted and repetitive behaviors.It is expected to provide a new theoretical basis and therapeutic targeting cell for the development and treatment of neuropsychiatric diseases related to restricted and repetitive behaviors in the future.
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Objective:To assess the association of appendicular skeletal muscle mass(ASM) to fat mass(FM) ratio in early pregnancy with the risk of gestational diabetes mellitus (GDM).Methods:A total of 468 pregnant women who visited the Nutritional Department of Peking Union Medical College Hospital or Shunyi Maternal and Child Care Service Center in 2018 and 2019 were recruited. Detailed information and clinical data were collected. The body components were measured using the bioelectrical impedance analysis (BIA) method during early pregnancy (< 14 weeks) and the ASM to FM ratio was calculated. The patients were divided into the GDM group and normal glucose tolerance (NGT) group according to the results of the oral glucose tolerance test (OGTT) performed during 24-28 weeks. Binary logistics regression was used to explore the correlation between the ASM/FM ratio and the risk of GDM. The receiver operator characteristic (ROC) curve of subjects was used to evaluate the predictive value of ASM/FM ratio for GDM and the cut-off value was reported.Results:Compared to the NGT group, the ASM and FM in early pregnancy in the GDM group were significantly higher, while the ASM/FM ratio was significantly lower. A lower ASM/FM ratio in early pregnancy was one of the risk factors of developing GDM. The cut-off value of the ASM/FM ratio was 0.809. The area under the ROC curve for predicting GDM increased from 68.1% to 72.3% when ASM/FM ratio was incorporated, with a significant difference by Delong test ( P = 0.006). Conclusion:Inadequate muscle mass would increase the risk of GDM and the ASM/FM ratio could serve as a predictor of GDM.
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Objective:To investigate the application effect of case-based learning (CBL) combined with flipped classroom in the teaching of experimental diagnostics in the integrated course of Diagnosis and Treatment Fundamentals. Methods:The cluster random sampling method was used to select the class of 2019 in the eight-year program and the class of 2020 in the five-year program, with the major of stomatology in Air Force Medical University. The 24 students in the observation group received CBL combined flipped classroom, and the 37 students in the control group received traditional teaching. The two groups were compared in terms of theoretical assessment score, classroom assessment score, comprehensive ability, self-learning ability, and degree of satisfaction with teaching. SPSS 22.0 was used for the t-test. Results:The observation group had a significantly higher theoretical assessment score than the control group [(74.88±3.46) vs. (71.89±4.45), P<0.05]. The observation group had significantly better scores of practical skill assessment than the control group ( P<0.05). Compared with the control group, the observation group had significantly better scores of comprehensive ability and self-learning ability ( P<0.05). The observation group had significantly better scores of satisfaction with teaching than the control group ( P<0.05). Conclusion:The application of CBL combined with flipped classroom in the teaching of experimental diagnostics in the integrated course of Diagnosis and Treatment Fundamentals can improve theoretical knowledge, practical skills, comprehensive quality, and satisfaction with teaching among students, and therefore, it holds promise for application in teaching.
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Practice teaching is an important link in the training of public health talents in colleges and universities. At present, there are still some problems in the education of public health and preventive medicine in the colleges and universities in China, such as attaching greater importance to theory than to practice and weak training of practical skills among students. In view of this situation, a public health practice teaching model of "internal-external interactions" has been constructed in Dalian Medical University with focuses on the following aspects: ①experiments in the university are optimized based on social needs; ②the practice base outside the university is expanded based on the teaching in the university; ③"internal-external interactions" are adopted to enhance practice training and improve post competence. The teaching practice shows that the implementation of the teaching model of "internal-external interactions" can help to improve practice teaching ability, promote the improvement in the training quality of public health talents, and meet the social demand for application-oriented professionals.
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Objective:To investigate the effect of rumination on learning burnout of nursing undergraduate students and the mediating role of psychological capital between rumination and learning burnout of nursing undergraduate students.Methods:A total of 296 undergraduate nursing students from three medical colleges were assessed by using ruminative responses scale, learning burnout questionnaire and psychological capital scale. SPSS 20.0 was used for t-test. Pearson correlation was to analyze the relationship among psychological capital, learning burnout and ruminative thinking. AMOS 20.0 was used to construct and analyze the mediating model of psychological capital and its mediating effect was tested by Bootstrap method. Results:The average score of rumination of nursing undergraduate students was 46.60±11.40, learning burnout score was 56.18±11.25, and psychological capital scale score was 99.93±15.27. There was a significant difference among the rumination, psychological capital, and learning burnout scores in whether there was curriculum failure ( P < 0.05). The total score of rumination was positively related to the total score of learning burnout ( r = 0.39, P < 0.01), and was negatively related to the total score of psychological capital ( r = -0.53, P < 0.01). The total score of rumination was negatively related to the total score of psychological capital ( r = -0.46, P < 0.01). The psychological capital played a partial mediating role between rumination and learning burnout. The mediating effect value was 0.216, accounting for 61.521% of the total variation. Conclusion:The rumination can both directly affect the learning burnout of nursing undergraduate students and indirectly affect the learning burnout through psychological capital. Psychological capital plays a bridge role in improving rumination related to learning burnout.
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ObjectiveTo compare the short-term effectiveness of the three different manipulations for atlantoaxial joint disorders and their effects on surface electromyography of sternocleidomastoid muscle. MethodsNinty patients with atlantoaxial joint disorders were randomly divided into the tendon relaxing manipulation group， the tendon relaxing plus rehabilitation manipulation group， and the conventional manipulation group， with 30 cases in each group， and each group of patients received the corresponding manipulation treatment for 2 weeks. The changes of visual analogue score （VAS） of occipital neck pain， evaluation scale for cervical vertigo （ESCV）， and averaged electromyography （AEMG） of surface electromyography of bilateral sternocleidomastoid muscles before and after the treatment were observed， and the clinical effectiveness and safety of the patients were compared among groups. ResultsThe VAS scores of patients in each group decreased， and the ESCV scores increased after treatment （P＜0.01）， and the tendon relaxing manipulation group and the tendon relaxing plus rehabilitation manipulation group were significantly better than the conventional manipulation group （P＜0.01）. The AEMG of the bilateral sternocleidomastoid muscles of the three groups increased after treatment （P＜0.01）； when compared among the three groups， the AEMG of the bilateral sternocleidomastoid muscles of the tendon relaxing plus rehabilitation manipulation group was higher than that of the tendon relaxing manipulation group， and the tendon relaxing manipulation group was higher than that of the conventional manipulation group （P＜0.05 or P＜0.01）. The cure and markedly effective rates of the tendon relaxing manipulation group， the tendon relaxing plus rehabilitation manipulation group， and the conventional manipulation group were 56.67%， 86.67%， and 36.67% respectively， showing statistically difference （K=10.21， P＜0.01）. ConclusionThe tendon relaxing manipulation and tendon relaxing plus rehabilitation manipulation can effectively improve the symptoms of vertigo， headache， and neck pain for patients with atlantoaxial joint disorders， and can improve the contraction function of sternocleidomastoid muscle， whose effectiveness are better than that of conventional manipulation.
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Background@#and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. @*Methods@#This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. @*Results@#Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). @*Conclusion@#In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.
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AIM: To revise the referral criteria for the SPOT Vision Screener in children under 6 years old and assessed its accuracy based on the American Association for Pediatric Ophthalmology and Strabismus(AAPOS)uniform guidelines for instrument-based pediatric vision screen validation 2021.METHODS: Children who visited the Maternal and Child Health Center of Yuhuatai District in Nanjing city from January 2022 to April 2023 were included in the study and underwent SPOT refractive screening, cycloplegic retinoscopy, and other examinations. Abnormal children were defined according to AAPOS guidelines with amblyopia risk factors(ARFs)and visually significant refractive error(VSRE). Receiver operating characteristic(ROC)curve was used to calculate the optimal referral criteria and compared with manufacturer criteria, Wu's criteria, and Peterseim's criteria.RESULTS: A total of 959 children were examined, with 342 in the <4-year-old group and 617 in the ≥4-year-old group. The optimal referral criteria for the <4-year-old group were myopia ≤-2.75 D, hyperopia ≥+2.25 D, astigmatism ≤-2.75 D, and anisometropia ≥1.00 D. For the ≥4-year-old group, the criteria were myopia ≤-1.75 D, hyperopia ≥+2.00 D, astigmatism ≤-2.25 D, and anisometropia ≥1.00 D. The Youden index was 0.38 and 0.52, respectively, which were higher than other criteria.CONCLUSION: The use of new referral criteria for refractive screening in children under 6 years old demonstrates higher accuracy compared to previous criteria. It provides valuable guidance for pediatric eye care and vision health in children.
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Thyroid-associated ophthalmopathy(TAO)is an autoimmune disease associated with thyroid dysfunction that can significantly impact quality of life, result in visual impairment and facial disfigurement. Traditional treatments are often unsatisfactory. Studies have shown that teprotumumab, a human monoclonal antibody that can inhibit insulin-like growth factor 1 receptor(IGF-1R), has become an emerging targeted drug for TAO. Although the drug has proven to be effective and relatively safe in the treatment of TAO, adverse reactions are worthy of attention of ophthalmologists with the continuous promotion of clinical application, including hearing impairment, hyperglycemia, diarrhea, muscle spasms, infusion reactions, cognitive decline, thyroid suppression, alopecia, nausea and fatigue. Teprotumumab was generally well tolerated, with most adverse events being mild or moderate in severity. This paper aims to review the adverse reactions and precautions of teprotumumab in the treatment of TAO.
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ObjectiveTo observe the clinical efficacy and safety of treating mediate-risk pure ground glass pulmonary nodules （pGGNs） based on the state theory. MethodsA prospective clinical randomized controlled trial was used. Totally 141 cases of mediate-risk pGGNs were divided into treatment group （92 cases） and control group （49 cases） according to the random table method. The treatment group was given the basic Sanjie Formula （基础散结方） orally with modification according to the identification of traditional Chinese medicine （TCM） state， 1 dose per day， 3 months as a course of treatment.Three months after the treatment patients were checked by CT. Patients who were clinically judged as cure， moderate to low risk， and turned to surgical resection do not carry out a second course of treatment，and the rest of the patients continued to complete the second courses. Patients in the control group did not receive any treatment and were only followed up periodically. Patients in both groups received a CT review 3 months and 6 months after enrolled. Comprehensive curative effect was evaluated according to the reduction rate of the area of pulmonary nodules shown in chest CT， to further explore the clinical effective difference for patients at different TCM state； the risk of malignancy index （Mayo score） was calculated by Mayo model at enrollment and 3 months and 6 months after enrolled. Adverse events were monitored continuously during the study. ResultsDuring the follow-up， 8 cases in the treatment group and 7 cases in the control group were lost. A total of 126 cases completed the whole process， including 84 cases in the treatment group and 42 cases in the control group. The total effective rates at 3 months and 6 months of the treatment group were 46.15% （30/65） and 45.71% （32/70） in the treatment group， while the total effective rates at 3 months and 6 months in the control group were 12.5% （4/32） and 10.00% （4/40）. Compared with the control group， the comprehensive curative effect of 3 months and 6 months of enrollment in treatment group was significantly better than that in corresponding control group （P＜0.01）. The pulmonary nodule area and Mayo score in the treatment group decreased after 3 and 6 months of enrollment （P＜0.01）. In contrast， there was no statistically significant difference in nodule area between pre- and post-enrollment time points in the control group （P＞0.05）， and probability of Mayo risk increased in the control group after 6 months of enrollment compared to pre-enrollment （P＜0.05）. Among the 84 patients in the treatment group， there were 15 cases of qi deficiency state， 7 cases of yin deficiency state， 5 cases of yang deficiency state， 20 cases of qi depression state， 32 cases of damp-heat state， and 5 cases of harmonious state； the difference in the distribution of the total clinical effective rate of the patients with different TCM states after treatment was statistically significant （P＜0.05）， and the total effective rate of two-by-two comparison of qi depression state was higher （13/20，65.00%） than that of the total effective rate of damp-heat state （8/32，25.00%， P＜0.00833）. There were no significant changes in blood routine， urine routine， liver function and kidney function in both groups， and no adverse events occurred. ConclusionTreating mediate-risk pGGNs based on the state theory can effectively reduce the area of pulmonary nodules and inhibit the growth of malignant risk of pulmonary nodules.
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Objective:To investigate the relationship between the expression patterns of SMG family members and aortic dissection by comparing the expression levels of SMGs in aortic wall of patients with Stanford type A aortic dissection(AD) and normal controls.Methods:The aortic wall samples were collected from 31 normal controls and 65 patients with Stanford type A aortic dissection. The mRNA levels of SMGs in the aortic wall were quantified by RT-PCR, and the correlations between SMGs and aortic diameters of patients with aortic dissection were analyzed.Results:The results of RT-PCR showed that compared with normal aortic wall, the mRNA levels of SMG3(0.642±0.529 vs. 1.126±0.858, P=0.023), SMG6(0.737±0.652 vs. 1.877±1.902, P=0.005), and SMG7(0.624±0.449 vs. 1.339±0.866, P=0.00067) were obviously increased in aortic wall of patients with aortic dissection, while comparable mRNA levels of SMG1, SMG2, SMG4, SMG5, SMG8 and SMG9 were detected between these two groups. In addition, there was no significant correlation between the expression levels of SMG3, SMG6, SMG7 and aortic diameters. Conclusion:The expression levels of SMG3, SMG6 and SMG7mRNA were significantly increased in patients with aortic dissection, suggesting that they may promote the occurrence of aortic dissection, and targeting SMG family members expected to a novel strategy for the prevention and treatment of aortic dissection.
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Objective:To explore anti-seizure medication (ASM) treatment patterns, seizures, maternal and fetal outcomes and offspring outcomes of pregnant women with epilepsy (PWWE) who withdraw ASM in the first trimester of pregnancy.Methods:A retrospective analysis was performed on the PWWE database registered in West China Hospital, Sichuan University from January 2009 to October 2022. Patients who withdrew ASM therapy in the first trimester and those who maintained ASM therapy throughout pregnancy were included. Withdrawal in the first trimester was defined as discontinuation of ASM between 0 and 3 months of pregnancy. Sixty-five PWWE (withdrawal group) who withdraw ASM in the first trimester were included, and 130 PWWE (maintained-therapy group) who took ASM throughout pregnancy in West China Hospital during the same period were matched 1∶2. Demographic characteristics, ASM, seizures, maternal and fetal outcomes within 1 year were compared between the 2 groups. In the subgroup analysis, the withdrawal group was divided into a full withdrawal group ( n=53) and a resumption group ( n=12) according to whether the ASM was resumed in the second and third trimesters of pregnancy, and the 2 groups were stratified and compared. Results:In the withdrawal group, the proportion of patients with bachelor degree below [72.3% (47/65) vs 54.6% (71/130), χ 2=5.68, P=0.017], family income less than 5 000 yuan per capita [44.6% (29/65) vs 18.5% (24/130), χ 2=14.98, P<0.001], a family history of epilepsy [12.3% (8/65) vs 3.1% (4/130), χ 2=4.90, P=0.027], and a second pregnancy [43.1% (28/65) vs 26.2% (34/130), χ 2=5.72, P=0.017] was higher than in the maintained-therapy group. The proportion of patients who received multiple ASM was lower in the withdrawal group than in the maintained-therapy group [16.9% (11/65) vs 38.5% (50/130), χ 2=9.35, P=0.002]. In the withdrawal group, the rate of seizures with tonic-clonic seizures during pregnancy [50.8% (33/65) vs 31.5% (41/130), χ 2=6.81, P=0.009] and seizure exacerbation during pregnancy [32.3% (21/65) vs 9.2% (12/130), χ 2=16.41, P<0.001] was higher. The preterm birth rate in the withdrawal group was lower than that in the maintained-therapy group [4.6% (3/65) vs 19.2% (25/130), χ 2=101.70, P<0.001]. The rate of seizure exacerbation during pregnancy was higher in the resumption group than in the full withdrawal group [7/12 vs 26.4% (14/53), χ 2=3.22, P=0.073]. Conclusions:PWWE with a family history of epilepsy and a second pregnancy were more likely to withdraw ASM during pregnancy. After withdrawal, the seizures during pregnancy were significantly worse, but the preterm birth rate of offspring was relatively reduced.
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Objective:To explore the association between the preoperative nocturnal blood pressure pattern and postoperative complications in elderly patients undergoing laparoscopic gastrointestinal surgery.Methods:A prospective observational cohort study was conducted in 131 elderly patients undergoing elective laparoscopic gastrointestinal surgery under general anesthesia between September 2018 and September 2021.All subjects underwent 24 h ambulatory blood pressure monitoring 1 day before surgery and, based on the nocturnal blood pressure pattern, patients were divided into two groups.Those with the nocturnal blood pressure reduction rate ≥0% entered the nocturnal blood pressure reduction group(Group D, n=80), and those with the reduction rate <0% entered the nocturnal blood pressure increase group(Group R, n=51). Differences in postoperative complication rates between the two groups were compared, and multivariate Logistic regression was used to analyze the influencing factors of postoperative complications.Results:(1)Compared with Group D, the prevalence of diabetes and left ventricular mass index were significantly increased and the mean nighttime SBP and DBP were significantly increased in Group R( P<0.05); (2)Compared with Group D, the incidence of acute kidney injury and acute heart failure in Group R was significantly higher( P<0.05), with the relative risk( RR)values at 2.941(95% CI: 1.344-6.435)and 3.660(95% CI: 0.991-13.512), respectively; (3)Multivariate Logistic regression analysis showed that elevated blood pressure at night was an independent risk factor for acute kidney injury after surgery( OR=3.700, 95% CI: 1.286-10.648, P=0.015); (4)Kaplan-Meier curves for acute kidney injury and acute heart failure showed that the cumulative incidence of events in Group R was significantly higher than that in Group D(Log rank test: P<0.05). Conclusions:For elderly patients undergoing selective laparoscopic gastrointestinal surgery, preoperative nocturnal blood pressure patterns were associated with postoperative complications.Elevated preoperative nocturnal blood pressure increases the incidence of postoperative acute kidney injury and heart failure, and elevated nocturnal blood pressure is an independent risk factor for acute kidney injury.
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Pancreatic cancer has an insidious onset and lacks effective treatment methods, which is one of the tumors with the worst prognosis, so it is urgent to explore new treatment directions. Metabolic reprogramming is one of the important hallmarks of tumors. Pancreatic cancer cells in the harsh tumor microenvironment have comprehensively increased cholesterol metabolism in order to maintain strong metabolic needs, and cancer associated fibroblasts also provide cancer cells with a large amount of lipids. Cholesterol metabolism reprogramming involves the changes in the synthesis, uptake, esterification and metabolites of cholesterol, which are closely related to the proliferation, invasion, metastasis, drug resistance, and immunosuppression of pancreatic cancer. Inhibition of cholesterol metabolism has obvious anti-tumor effect. In this paper, the important effects and complexity of cholesterol metabolism in pancreatic cancer were comprehensively reviewed from perspectives of risk factors for pancreatic cancer, energy interaction between tumor-related cells, key targets of cholesterol metabolism and its targeted drugs. Cholesterol metabolism has a strict regulation and feedback mechanism, and the effect of single-target drugs in clinical application is not clear. Therefore, multi-target therapy of cholesterol metabolism is a new direction for pancreatic cancer treatment.
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Humanos , Neoplasias Pancreáticas/patología , Colesterol/metabolismo , Microambiente TumoralRESUMEN
BACKGROUND@#Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism.@*METHODS@#GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis.@*RESULTS@#B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02).@*CONCLUSIONS@#B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
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Humanos , Línea Celular Tumoral , Recurrencia Local de Neoplasia , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Neoplasias GástricasRESUMEN
The prevalence of obesity has increased worldwide in recent decades. Genetic factors are now known to play a substantial role in the predisposition to obesity and may contribute up to 70% of the risk for obesity. Technological advancements during the last decades have allowed the identification of many hundreds of genetic markers associated with obesity. However, the transformation of current genetic variant-obesity associations into biological knowledge has been proven challenging. Genomics and proteomics are complementary fields, as proteomics extends functional analyses. Integrating genomic and proteomic data can help to bridge a gap in knowledge regarding genetic variant-obesity associations and to identify new drug targets for the treatment of obesity. We provide an overview of the published papers on the integrated analysis of proteomic and genomic data in obesity and summarize four mainstream strategies: overlap, colocalization, Mendelian randomization, and proteome-wide association studies. The integrated analyses identified many obesity-associated proteins, such as leptin, follistatin, and adenylate cyclase 3. Despite great progress, integrative studies focusing on obesity are still limited. There is an increased demand for large prospective cohort studies to identify and validate findings, and further apply these findings to the prevention, intervention, and treatment of obesity. In addition, we also discuss several other potential integration methods.
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Humanos , Proteoma/metabolismo , Proteómica , Estudios Prospectivos , Obesidad/genética , Genómica , Estudio de Asociación del Genoma CompletoRESUMEN
OBJECTIVE@#To observe the effect of electroacupuncture (EA) on liver protein kinase B (Akt)/forkhead box transcription factor 1 (FoxO1) signaling pathway in Zucker diabetic fatty (ZDF) rats, and to explore the possible mechanism of EA on improving liver insulin resistance of type 2 diabetes mellitus.@*METHODS@#Twelve male 2-month-old ZDF rats were fed with high-fat diet for 4 weeks to establish diabetes model. After modeling, the rats were randomly divided into a model group and an EA group, with 6 rats in each group. In addition, six male Zucker lean (ZL) rats were used as the blank group. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20). The ipsilateral "Zusanli" (ST 36) and "Weiwanxiashu" (EX-B 3) were connected to EA device, continuous wave, frequency of 15 Hz, 20 min each time, once a day, six times a week, for a total of 4 weeks. The fasting blood glucose (FBG) in each group was compared before modeling, before intervention and after intervention; the serum levels of insulin (INS) and C-peptide were measured by radioimmunoassay method, and the insulin resistance index (HOMA-IR) was calculated; HE staining method was used to observe the liver tissue morphology; Western blot method was used to detect the protein expression of Akt, FoxO1 and phosphoenolpyruvate carboxykinase (PEPCK) in the liver.@*RESULTS@#Before intervention, compared with the blank group, FBG was increased in the model group and the EA group (P<0.01); after intervention, compared with the model group, FBG in the EA group was decreased (P<0.01). Compared with the blank group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were increased (P<0.01), while the protein expression of hepatic Akt was decreased (P<0.01) in the model group. Compared with the model group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were decreased (P<0.01), while the protein expression of hepatic Akt was increased (P<0.01) in the EA group. In the model group, the hepatocytes were structurally disordered and randomly arranged, with a large number of lipid vacuoles in the cytoplasm. In the EA group, the morphology of hepatocytes tended to be normal and lipid vacuoles were decreased.@*CONCLUSION@#EA could reduce FBG and HOMA-IR in ZDF rats, improve liver insulin resistance, which may be related to regulating Akt/FoxO1 signaling pathway.
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Masculino , Animales , Ratas , Ratas Zucker , Proteínas Proto-Oncogénicas c-akt/genética , Diabetes Mellitus Tipo 2/terapia , Resistencia a la Insulina , Péptido C , Electroacupuntura , Hígado , Transducción de Señal , Insulina , LípidosRESUMEN
OBJECTIVE@#To observe the clinical effect of bloodletting at auricular dorsal vein combined with auricular point sticking on menstrual migraine (MM) of qi stagnation and blood stasis, and explore its possible mechanism.@*METHODS@#A total of 102 cases of MM with qi stagnation and blood stasis were randomly divided into an observation group (51 cases, 3 cases dropped off) and a control group (51 cases, 2 cases dropped off). The patients in the observation group were treated with bloodletting at auricular dorsal vein combined with auricular point sticking. The bloodletting was performed at vein at upper 1/3 of the dorsalis near the ear helix; the auricular point sticking was performed at Pizhixia (AT4), Neifenmi (CO18), Jiaogan (AH6a), Nie (AT2), Zhen (AT3), Shenmen (TF4) and Yidan (CO11). The auricular points of both ears were alternate used. From 7 days before the onset of menstruation, bloodletting at auricular dorsal vein was given once every 7 days, 3 times were taken as a course of treatment, and 1 course of treatment was given; the auricular point sticking was given once every 3 days, and 6 times of treatment were given. The patients in the control group were treated with oral administration of flunarizine hydrochloride capsules. From 7 days before the onset of menstruation, flunarizine hydrochloride was given 2 capsules per time, once a day for 3 weeks. The menstrual headache index and visual analogue scale (VAS) score of the two groups were observed before treatment, one menstrual cycle into treatment and the first and the second menstrual cycle after treatment; the migraine-specific quality of life questionnaire (MSQ) score and the serum levels of estradiol (E2) and 5-hydroxytryptamine (5-HT) were compared before treatment and one menstrual cycle into treatment; the clinical efficacy was evaluated at one menstrual cycle into treatment.@*RESULTS@#Compared before treatment, the menstrual headache index and VAS scores were reduced at one menstrual cycle into treatment and the first and second menstrual cycle after treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Compared before treatment, the MSQ scores and the serum levels of E2 and 5-HT in the two groups were increased at one menstrual cycle into treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The total effective rate was 95.8% (46/48) in the observation group, which was higher than 73.5% (36/49) in the control group (P<0.05).@*CONCLUSION@#Bloodletting at auricular dorsal vein combined with auricular point sticking could relieve headache intensity, improve the quality of life in patients with MM of qi stagnation and blood stasis, which may be achieved by raising the serum levels of E2 and 5-HT to improve the level of hormone in the body.