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OBJECTIVE To systematically evaluate the efficacy and safety of olaparib in adjuvant therapy of breast cancer susceptibility gene （BRCA） 1/2 mutated human epidermal growth factor receptor 2 （HER2）-negative breast cancer， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from CNKI， VIP， Wanfang data， PubMed， ScienceDirect， the Cochrane Library and Embase databases， randomized controlled trials about adjuvant therapy of olaparib （trial group） versus adjuvant therapy of other drugs （control group） were collected. After literature screening and data extraction， meta-analysis， publication bias analysis and sensitivity analysis were performed by using RevMan5.4 software. RESULTS A total of 5 randomized controlled trials were included， with a total of 2 633 patients， including 1 495 cases in trial group and 1 174 cases in control group. Meta-analysis showed that in terms of efficacy， compared with control group， overall survival [HR＝1.02， 95%CI （1.01，1.03）， P＝0.000 8] and progression-free survival [HR＝1.78， 95%CI（1.46，2.17）， P＜0.000 01] were longer significantly in the trial group. In terms of safety， compared with the control group， the incidence of adverse drug reactions at any level in the trial group was higher [RR＝1.41， 95%CI （1.12， 1.78）， P＝0.004]， while there was no statistically significant difference in the incidence of adverse drug reactions above level 3 between the two groups [RR＝1.75， 95%CI （0.82， 3.74）， P＝0.15]. The results of publication bias indicated that the possibility of publication bias in this study was relatively low. The results of sensitivity analysis showed that the results obtained in this study were robust. CONCLUSIONS Compared with patients without adjuvant therapy of olaparib， adjuvant therapy of olaparib can prolong overall survival and progression-free survival of patients with BRCA1/2 mutated HER2-negative breast cancer，but the risk of adverse drug reactions is relatively high.
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Virtue ethics and normative ethics are corresponding ethical concepts, and their collision and integration promote the development of ethical system. On the issue of doctor-patient relationship, from virtue to norm is the objective requirement of social transformation and development, and is also the inevitable choice to resolve doctor-patient conflicts and reshape doctor-patient relationships. In the new era, the construction of doctor-patient relationship faces ethical dilemma such as one-sided emphasis on doctors’ virtue cultivation, unclear ethical responsibilities between doctors and patients, and lack of trust and tolerance between doctors and patients. Therefore, it is necessary to strengthen the institutionalization of doctor ethics, clarify the ethical responsibilities of both doctors and patients, optimize the social ethical ecological environment, so as to realize the ethical reconstruction of doctor-patient relationship from virtue to norm.
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The modern concept of lacunar infarct is largely based on the meticulous postmortem work of Fisher from the 1950s to 1970s, which forms the basis of the"lacunar hypothesis". Along with the application of CT or MRI techniques and classification of ischemic stroke subtypes, the lacunar infarct was endowed with the profile of imaging diagnosis and stroke subtypes. Thus, the concept of lacunar infarct has far expanded the initial pathological meanings and the terminology and definitions for lacunar infarct vary widely. In this review, the historical pathological findings and the term evolution of lacunar infarct were systemically reviewed, with a focus toward future directions in the complex entity of lacunar infarct.
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Survivors of intracerebral hemorrhage (ICH) have significantly higher risks of both arterial ischemic events and recurrent ICH after the first event. This uncertainty leaves clinicians with dilemmas about the therapy strategies for the secondary prevention of major vascular events after ICH. Clinicians mainly focus on the prevention of hemorrhage recurrence but overlook the increased risk of ischemic disease after ICH in routine clinical practice. Secondary stroke prevention measures after ICH including antithrombotic and statin treatments remain challenging due to the lack of dedicated studies with strong evidence. Decision-making on stroke prevention requires algorithmic approaches based on the hemorrhagic and ischemic risk stratification. This article systematically reviews the current evidence for the prevention and management of subsequent arterial ischemic events after ICH, aiming to promote further attention and research to address the current controversies and knowledge gap on this topic.
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In recent years, the "Room Escape" industry in China is booming, and this real live game has become popular. However, health threatening events such as fire, trauma, coma, and lung infection in the game venues have been reported at home and abroad. If these venues are not supervised in time, there will be great potential public safety and health hazards. In this review, we summarized the hidden dangers of public safety and health in such venues, including fire and safety hazards, persistent stress state, indoor ventilation problems, risk of contagious infection, non-player characters’ health risk, special film effects of 4D cinemas, mosquito problems, light pollution and noise, and food safety. Meanwhile, health management recommendations for the game venues were proposed from the aspects of formulating health management standards, improving health security measures, and strengthening related health education to players, so as to improve the hygiene levels of such venues and protect players and staff from injuries or diseases.
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Ossification of the spinal ligaments (OSL) is characterized by the appearance of pathologic bone tissue within the spinal ligamentous tissue. OSL tends to occur in the cervical and thoracic segments with important cause of spinal stenosis. Compression of the spinal cord or nerve roots by ossified masses can lead to severe neurological dysfunction, which has a tremendous impact on the quality of life of patients. However, the exact etiology and pathogenesis of OSL are still unclear. Epigenetic regulation is widespread in organisms and refers to the appearance of heritable changes in gene expression without alteration in genomic DNA sequence. As an important form of biodiversity regulation, epigenetic regulation plays an important role in development of several diseases. Epigenetic regulation has multiple manifestations in OSL, including DNA methylation, histone modifications, and non-coding RNA regulation. Sequencing tools, such as gene microarrays, have revealed significant differences in DNA methylation profiles and non-coding RNA expression between ossified and normal spinal ligaments. These differences can cause abnormal expression of osteogenesis-related target genes through direct or indirect pathways, thus affecting the ossification process of spinal ligaments. In addition, interactions between these epigenetic regulatory mechanisms constitute a large and complex regulatory network. Consequently, an in-depth understanding of the role of different epigenetic regulatory mechanisms and the linkages between them in the initiation and progression stages of OSL is expected to provide a valuable reference for the clinical diagnosis and treatment of OSL-related diseases.
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Objective:To explore the predictive value of vertebral trabecular and endplate HU values on cage subsidence after posterior lumbar interbody fusion (PLIF), hope to provide reference for surgical planning.Methods:All of 72 patients with lumbar disc herniation that underwent PLIF were retrospectively reviewed, who were divided into two groups according to the occurrence of cage subsidence at one-year follow up. Cage subsidence was defined as more than 4 mm subsidence into the vertebrae valuated by CT at one-year follow up. There were 18 patients enrolled into Subsidence group and 54 patients enrolled into N-Subsidence group. The lumbar lordosis, segmental lordosis, intervertebral height, off-bed time, hospital stay, complications, the trabecular and endplate HU values of upper instrumented vertebrae (UIV) and lower instrumented vertebrae (LIV) were compared between the two groups. ROC was used to explore the thresholds of HU values.Results:There were 14 patients presented cage subsidence into the L4, 4 patients presented cage subsidence into the L5. There was no significant difference in lumbar lordosis, segmental lordosis, intervertebral height, off-bed time, hospital stay, or complications between the two groups. Both UIV and LIV trabecular and endplate showed a lower HU value in Subsidence group than those in N-Subsidence group. The most appropriate thresholds of HU value were 146, 172, 307, 254 for trabecular of UIV, trabecular of LIV, lower endplate of UIV, and upper endplate of LIV, respectively.Conclusion:Vertebral trabecular and endplate HU values could effectively predict the cage subsidence after PLIF, patients should be completely informed the risk of cage subsidence and larger cage should be recommended if they presented HU values under the certain threshold.
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Objective:To analyze the actual and expected incentives and key issues of telemedicine providers in China and to provide important references for optimizing telemedicine incentive policies.Methods:The sample data came from a questionnaire survey of 1 084 providers in 7 provinces of Fujian, Hainan, Henan, Hunan, Guizhou, Sichuan and Qinghai in October and November 2019 and a semi-structured interview data at 6 hospitals in Henan province in January 2020. Descriptive analysis was used to sort such data into text data for classified summation.Results:The greatest gaps were found between actual incentives and expected ones in expense subsidies, title promotion and excellence awards, with such gaps as high as 18.65, 28.26, 29.28 percentages among providers of junior, deputy senior and senior academic titles respectively. Hospitals fall short in providing adequate incentives for telemedicine providers, not to mention lack of differentiation and diversification in personnel incentives, and poor implementation of incentive policies.Conclusions:It is suggested to strengthen incentive demand analysis, break the homogenization bottleneck of incentive policies, and consolidate internal publicity and implementation of incentive policies.
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Objective:To analyze the usage intention and key issues of medical staff to use telemedicine, for improving telemedicine service system in China.Methods:From October to November 2019, medical workers of both the inviting party and invited party who experienced telemedicine in seven provinces of Fujian, Hainan, Henan, Hunan, Guizhou, Sichuan and Qinghai were selected for an online questionnaire survey. Areas covered included their usage intention, satisfaction and cognitive appraisal of telemedicine. Descriptive statistical analysis and non-parametric test were used to discuss the intention of further use, satisfaction and challenges of medical workers in various provinces and regions.Results:1 084 valid questionnaires were recovered. The data found the overall satisfaction was 98.62%, and the proportion of their intention of further use was 98.25%, and those from the eastern and western provinces presented higher intention of usage. The top challenges as reflected by these medical workers were named as follows: timeliness of consultation progress and information feedback; long latency time; low Internet speed, poor and interrupted Internet signal; inadequate system equipments and inconvenient operation; difficulties in remote physical checkup and overall understanding of patient conditions; as well as substandard, incomplete and poor medical records.Conclusions:These medical workers are satisfied with the telemedicine services and willing to continue to use telemedicine.For those existing problems, it is suggested to strengthen the infrastructure and optimize the process of telemedicine services, so as to encourage them in greater use of telemedicine.
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Objective:To investigate the effects of hydrogen rich-saline (HRS) on intestinal mucosal barrier in rat with intestinal ischemia/reperfusion injury (IIRI).Methods:Twenty-four healthy male Sprague-Dawley rats, aged 8 weeks, were randomly divided into 3 groups (8 in each group) by random number table method: sham group, model group and HRS group.Rats in HRS group were intraperitoneally injected with HRS (10 mL/kg) at 30 min of ischemia, and the same amount of normal saline was intraperitoneally injected in model group.After 45 min of ischemia and 6 h of reperfusion, rats were sacrificed.Serum and ileum were collected for further detection.Tumor necrosis factor alpha (TNF-α), interleukin (IL)- 1β and IL-17A expression levels in serum were detected by conducting enzyme-linked immunosorbent assay (ELISA). The localization expressions of tight junction protein Occludin was detected by immunohistochemical staining (IHC), while the localization expression of tight junction protein zonula occluden-1 (ZO-1) were detected by immunofluorescence staining (IF). The protein expression of Occludin, ZO-1, and Lysozyme were detected by performing Western blot.The mRNA expression of Lysozyme and α-defensin were detected by real-time PCR (qPCR).Results:ELISA results proved that the levels of serum TNF-α and IL-1β in HRS group rats were significantly lower than those in model group [(62.02±29.97) ng/L vs.(113.40±44.58) ng/L, (21.68±0.35) ng/L vs.(28.29±3.49) ng/L], while the level of IL-17A increased [(28.18±5.28) ng/L vs. (15.10±3.60) ng/L] (all P<0.05). IHC staining: compared with model group, the expression of Occludin in HRS group was uniform and continuous, and the staining was darker.IF results: compared with model group, the fluorescence signal intensity of ZO-1 in HRS group rats significantly increased, and the distribution was clear and continuous.Wes-tern blot results: compared with model group, the expression levels of Occludin and ZO-1 proteins in HRS group rats remarkably increased (0.79±0.06 vs. 0.54±0.04, 0.91±0.11 vs. 0.51±0.13), while Lysozyme protein decreased (1.50±0.40 vs. 2.99±0.80) (all P<0.05). qPCR results revealed that the expression level of Lysozyme mRNA in HRS group rats was lower than that in model group (1.64±0.33 vs. 2.20±0.40), while α-defensin mRNA obviously increased (0.82±0.19 vs. 0.47±0.13) (all P<0.01). Conclusions:HRS protects intestinal mucosal barrier by inhibiting the expression of tight junctions and the secretion of antimicrobial peptides in rat suffering from IIRI.
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Kunitz-type serine protease inhibitors are a class of ubiquitous protease inhibitors, which play important roles in various life activities. The structures of such inhibitors are generally stable, and are usually characterized by the presence of one or several Kunitz domains in tandem, which are able to bind to serine proteases in a manner similar to substrate binding, thereby inhibiting enzyme activity. In terms of function, Kunitz-type serine protease inhibitors are involved in processes such as blood coagulation and fibrinolysis, tumor immunity, inflammation regulation, and resistance to bacterial and fungal infections. This article summarizes the advances of Kunitz-type serine protease inhibitors and provides new ideas for the development of novel Kunitz-type serine protease inhibitors.
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Protease Inhibitors , Serine Proteases , Serine Proteinase InhibitorsABSTRACT
BACKGROUND@#Single subcortical infarction (SSI) is caused by two main etiological subtypes, which are branch atheromatous disease (BAD) and cerebral small vessel disease (CSVD)-related SSI. We applied the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ), the Shape Trail Test (STT), and the Stroop Color and Word Test (SCWT) to investigate the differences in cognitive performance between these two subtypes of SSI.@*METHODS@#Patients with acute SSIs were prospectively enrolled. The differences of MoCA-BJ, STT, and SCWT between the BAD group and CSVD-related SSI group were analyzed. A generalized linear model was used to analyze the associations between SSI patients with different etiological mechanisms and cognitive function. We investigated the correlations between MoCA-BJ, STT, and SCWT using Spearman's correlation analysis and established cut-off scores for Shape Trail Test A (STT-A) and STT-B to identify cognitive impairment in patients with SSI.@*RESULTS@#This study enrolled a total of 106 patients, including 49 and 57 patients with BAD and CSVD-related SSI, respectively. The BAD group performances were worse than those of the CSVD-related SSI group for STT-A (83 [60.5-120.0] vs. 68 [49.0-86.5], P = 0.01), STT-B (204 [151.5-294.5] vs. 153 [126.5-212.5], P = 0.015), and the number of correct answers on Stroop-C (46 [41-49] vs. 49 [45-50], P = 0.035). After adjusting for age, years of education, National Institutes of Health Stroke Scale and lesion location, the performance of SSI patients with different etiological mechanisms still differed significantly for STT-A and STT-B.@*CONCLUSIONS@#BAD patients were more likely to perform worse than CSVD-related SSI patients in the domains of language, attention, executive function, and memory. The mechanism of cognitive impairment after BAD remains unclear.
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Humans , Cerebral Infarction , Cerebral Small Vessel Diseases , Cognitive Dysfunction/etiology , Executive Function , Mental Status and Dementia TestsABSTRACT
Objective:To study the effect of adapted rhythmic gymnastics based on International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY) on the fundamental motor skill development for children with low function autism spectrum disorder (ASD). Methods:Three boys aged 7.2 to 8 years with low function ASD (IQ 47 to 53) participated in the exercise since September, 2019. Their activities and motor function were analyzed with ICF-CY to develop a 12-week rehabilitation exercise, including physical fitness, gymnastics skills content and game. They were assessed with ICF-CY based Questionnaire and gross motor of Peabody Developmental Motor Scales (PDMS-2) before and after training. Results:The qualifiers of body structure, body function, activity and participation improved somehow after training. The scores of gross motor skills of PDMS-2 improved. Conclusion:The adapted rhythmic gymnastics training based on ICF-CY may improve the functioning, especially motor function, for children with low function ASD, which can be a kind of rehabilitation exercise.
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Selenium is an essential trace element in many living organisms. Selenium deficiency inhibits cell differentiation and cell cycle progression, induces apoptosis and increases the virulence of certain viruses. In addition, selenium deficiency is an important etiology of Keshan disease and a risk factor for cardiovascular disease. Low selenium studies based on in vitro cell experiments are widely used. However, there is currently no clear and unified way to establish in vitro low-selenium conditions. In this paper, we have reviewed the progress on establishment of low-selenium conditions in vitro and its applications, so as to provide reference for subsequent study.
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Objective@#To observe the dynamic impacts of shock waves on the severity of lung injury in rats with different injury distances.@*Methods@#Simulate open-field shock waves; detect the biomechanical effects of explosion sources at distances of 40, 44, and 48 cm from rats; and examine the changes in the gross anatomy of the lungs, lung wet/dry weight ratio, hemoglobin concentration, blood gas analysis, and pathology.@*Results@#Biomechanical parameters such as the overpressure peak and impulse were gradually attenuated with an increase in the injury distance. The lung tissue hemorrhage, edema, oxygenation index, and pathology changed more significantly for the 40 cm group than for the 44 and 48 cm groups. The overpressure peak and impulse were significantly higher for the 40 cm group than for the 44 and 48 cm groups ( < 0.05 or < 0.01). The animal mortality was significantly higher for the 40 cm group than for the other two groups (41.2% . 17.8% and 10.0%, < 0.05). The healing time of injured lung tissues for the 40 cm group was longer than those for the 44 and 48 cm groups.@*Conclusions@#The effects of simulated open-field shock waves on the severity of lung injuries in rats were correlated with the injury distances, the peak overpressure, and the overpressure impulse.
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Animals , Male , Rats , Biomechanical Phenomena , Blast Injuries , Pathology , Disease Models, Animal , Explosions , Lung Injury , Pathology , Random Allocation , Rats, Sprague-DawleyABSTRACT
Objective:To explore the influencing factors of telemedicine system operation and identify the relationship among them, so as to provide policy suggestions for promoting the healthy operation of telemedicine service system.Methods:The published literatures from January 2009 to December 2019 were searched, and the factors influencing the operation of telemedicine service system were preliminarily screened out. The influencing factors were evaluated and scored by expert consultation method(0-5 points). Then the influencing factors and their relationship were analyzed by decision-making trial and evaluation laboratory method.Results:A total of 16 influencing factors, including 6 cause factors and 10 result factors, were selected. In the cause factors, leadership support, supervision mechanism and incentive compatibility mechanism were in the top three; among the outcome factors, disease information communication, patient participation and medical service quality were more susceptible to other factors.Conclusions:It is helpful to promote the healthy and sustainable operation of telemedicine service system by enhancing the attention of the leaders of medical institutions, building a perfect regulatory mechanism and incentive compatible mechanism, ensuring the effective communication of disease information by doctors of upper and lower medical institutions, and improving the participation of patients and the quality of medical services.
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Objective:To explore the risk factors of acute kidney injury(AKI) in patients after radical nephrectomy.Methods:We retrospectively collected clinical information of 920 patients with renal cell carcinoma who underwent radical nephrectomy at Zhongshan Hospital, Fudan University from February 2013 to September 2017. There were 612 male and 308 female patients included in this study, with a median age of 60 (range from 20-75 years). 313 patients (34.0%) had hypertension, 132 patients (14.3%) had diabetes, and 111 patients (12.1%) had smoking history. 829 cases (90.1%) were in stage 1-2 for preoperative renal function staging, and 91 cases (9.9%) were in stage 3-5. Preoperative hemoglobin was lower than the lower limit of normal in 391 cases (42.5%), white blood cell count increased in 66 cases (7.2%), and platelet increased in 72 cases (7.8%). Albumin was lower than the lower limit of normal in 65 cases (7.1%), lactate dehydrogenase increased in 73 cases (7.9%). blood urea nitrogen increased in 48 cases (5.2%), uric acid increased in 123 cases (13.4%), and urinary protein was positive in 88 cases (9.7%). 496 cases (53.9%) underwent open surgery and 424 (46.1%) underwent laparoscopic surgery. The changes in serum creatinine were followed up within 48 hours after surgery. AKI was defined according to the KDIGO standard. Logistic regression was used to analyze the risk factors for postoperative stage 2-3 AKI in patients.Results:Stage 1-3 AKI occurred on 627, 42 and 10 patients during hospitalization, respectively. Univariate analysis showed that diabetes ( OR=2.34, P=0.01), positive urine protein ( OR=2.22, P=0.04), and elevated white blood cell count ( OR=2.54, P=0.02) were significantly associated with postoperative stage 2-3 AKI. Multivariate logistic regression analysis showed that diabetes ( OR=2.51, P=0.01) and elevated white blood cell count ( OR=2.69, P=0.02) were independent risk factors for postoperative stage 2-3 AKI. Conclusion:Renal cell carcinoma patients with diabetes or preoperative elevated white blood cell count are more likely to develop stage 2-3 AKI after radical nephrectomy.
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Cerebral microblecds (CMBs) are one of the imaging phenotypes of cerebral small vessel disease.With the continuous development of imaging technology,the detection rate of CMBs is getting higher and higher,and its close relationship with cognitive impairment is receiving more and more attention.This article review s the risk factors,epidemiology,and the correlation between the location and number of CMBs and the functional impairment of different cognitive domains.
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Cerebral microbleeds (CMBs) are one of the imaging phenotypes of cerebral small vessel disease. With the continuous development of imaging technology, the detection rate of CMBs is getting higher and higher, and its close relationship with cognitive impairment is receiving more and more attention. This article reviews the risk factors, epidemiology, and the correlation between the location and number of CMBs and the functional impairment of different cognitive domains.
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Silent information regulator 1(SIRT1)belongs to nicotinamide adenine dinucleotide(a classic coenzyme) dependent class Ⅲ histone deacetylases.SIRT1 regulates gene expression through altering the acetylation level of nuclear histone and participates in the regulation of a range of important life activities,such as cardiomyocyte autophagy,nucleocytoplasmic shuttling,cell aging,inflammatory responses,etc.It has been showed that SIRT1 plays an important role in myocardial ischemia by mitigating cardiomyocyte apoptosis and enhancing cellular resistance to oxidative stress under ischemic conditions.This article gives an overview of the mechanisms and research progress of SIRT1 in myocardial ischemia,aiming to serve as a reference for myocardial ischemia therapy.