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The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.
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Objective To understand the epidemiological characteristics and genotype distribution of enterovirus (EV) in influenza-negative influenza-like illness (ILI) cases in Chongqing, and to provide a scientific basis for EV prevention and control. Methods Throat swab samples of influenza-negative ILI cases were collected from surveillance sites. The samples were detected for EV using real-time RT-PCR. The VP4 regions of positive samples were amplified and sequenced for genotyping. Results A total of 3 960 influenza-negative ILI samples were collected from January to December 2021, and 316 (7.98%) of them were EV-positive. EV could be detected in influenza-negative ILI cases in Chongqing all year round. The months with high EV-positive rates were January (11.60%), April (10.56%), May (11.79%), June (12.62%), and July (10.33%). There was a statistically significant difference in the detection rate of EV in ILI cases in different regions, gender, and age groups (χ2=29.647，χ2=4.192，χ2=69.176，P<0.05). A total of 213 EV-positive cases were successfully genotyped, including 17 genotypes of EV-A, EV-B, and EV-C and 5 genotypes of HRV-B. The dominant genotypes were CV-A4 (32.86%), CV-A2 (23.00%), CA-6 (12.21%), and CA-10 (11.74%). EV-D and novel EV were not identified in this study. Conclusion EV is an important pathogen in ILI cases in Chongqing. The prevalence of EV in ILI cases in Chongqing has typical regional, seasonal and population characteristics. Prevention and control should be carried out in Chongqing according to the epidemic characteristics of EV.
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Objective To evaluate the noise hazard level of a coal mining enterprise, and identify high-risk operation types and people, and to provide a basis for preventing and controlling the health damage caused by noise. Methods A large coal mining enterprise in Shaanxi Province was selected as the research object. The noise monitoring data of the coal mine over the years was used to calculate the noise exposure matrix of each post in the enterprise, and the classification of occupational hazards at workplaces (GBZ/T 229.4-2012) was used to assess the occupational health risk levels. Results Among the 22 noise-exposed positions in the enterprise, the 8-hour working day equivalent sound level in positions of shearer driver, horseshoe driver, crusher driver, shuttle driver, relaxation screen driver, and grading screen driver were all higher than the occupational exposure limit of noise. In 2021, the noise exposure levels of shearer drivers, crusher drivers, and coal-selecting workers were all higher than 90 dB (A), and the occupational hazard level was moderate hazard level. In addition, the noise exposure levels of most other jobs also exceeded the occupational exposure limit. Conclusion The noise hazards in the coal mine industry are mainly concentrated in the posts of the coal mining system, tunneling system, and screening workshop. Among them, the shearer driver, the crusher driver, and the coal preparation workers have higher noise exposure levels. It is recommended to take corresponding noise reduction measures and strengthen the protection level to reduce the noise exposure risk of workers.
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Objective:To determine the accuracy of injury severity score(ISS)in the assessment of patients with severe trauma by the consistency analysis of the patients'ISS with severe trauma scored by three clinicians,and to guide the allocation of medical resource.Methods:Through retrospective analysis of 100 patients with serious or severe trauma admitted to Peking University People's Hospital since Sep-tember 2020 to December 2021(ISS ≥ 16 points),we conducted a consistency analysis of ISS within dif-ferent evaluators.The general information(gender,age),vital signs,physical examination,imaging,laboratory examination and other associated data of the patients after admission were retrospectively diag-nosed by 3 clinicians specializing in trauma surgery and ISS was determined.SPSS 22.0 software was used for statistical analysis,descriptive reports were made on the observed values of each set of data,and Fleiss kappa test was used for consistency analysis of the credibility of the ISS within three clinicians.Results:Through the consistency analysis of the ISS in 100 patients with severe trauma scored by 3 eva-luators,the total Fleiss kappa value was 0.581,and the overall consistency was medium.Consistency analysis of the different scores was conducted according to the calculation rules of ISS.Among the patients with single-site severe trauma,abbreviated injury scale(AIS)was 4 or 5 points,ISS was 16 or 25 points,and Fleiss kappa value was 0.756 and 0.712 within the three evaluators,showing a relatively high consistency.AIS of each part was more than 4 points,and total ISS was more than 41 points in the severe trauma patients,Fleiss kappa values are higher than 0.8 within the 3 evaluators,showing a high consistency.Conclusion:According to the consistency analysis of severe trauma patients ISS within the three evaluators,when the severe trauma patients with ISS≥16 points are treated or transported,there is a certain accuracy error when the score is used for inter-department communication or inter-hospital trans-portation,and the consistency of different evaluators for the same injury is moderate.It may lead to mis-judgment of the severity of trauma and misallocation of medical resources.However,for trauma patients with single or multiple site AIS ≥ 4 points,ISS is highly consistent among different evaluators,which can accurately indicate the severity of the patient's condition.
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Objective:To analyze the clinical characteristics of hemodialysis patients with corona virus disease 2019(COVID-19)in a single-center from Beijing.Methods:Patients with COVID-19 who re-ceived regular hemodialysis at Peking University Third Hospital from November 30,2022 to January 4,2023 were selected as the study objects.Clinical symptoms,severity and duration of symptoms during the period of virus positive were investigated in the form of questionnaires,and the basic information of the patients,as well as the results of blood tests(routine blood and blood biochemistry,etc.)before and af-ter infection,dialysis treatment and the outcome of the disease were collected by consulting medical re-cords.Results:A total of 203 subjects were included in this study,including 148 mild cases(72.91％),23 medium cases(11.33％),32 severe and critical cases(15.76％),and 16(7.88％)deaths occured during the follow-up.Clinical symptoms mainly included respiratory symptoms(among which 81.77％had cough,68.97％had expectoration),fever(81.28％)and fatigue(65.52％),and fatigue and weakness had the longest duration[9(5,15)days]among all symptoms.Twenty-six patients(12.8％)reduced the dialysis sessions[1(1,2)times],25 patients(12.32％)had the behavior of early finishing dialysis(27 times),reducing the dialysis time by 30.0(20.0,30.5)minutes.Univa-riate analysis showed that the hemoglobin,creatinine,urea nitrogen and ultrafiltration decreased signi-ficantly after infection(P＜0.05).There were significant differences in age,albumin,hemoglobin,creatinine levels and vascular access types among the patients with different clinical subtypes,and the changes of dialysis sessions,fever,expectoration and fatigue degree were also different among the patients with different clinical subtypes(P＜0.05).Multivariate Logistic regression analysis showed that age(OR=1.051,95％CI:1.017-1.086,P=0.003)and albumin levels(OR=0.905,95％CI:0.803-1.019,P=0.098)corrected by fever,expectoration and fatigue levels were still associated with the oc-currence of pneumonia.Conclusion:The morbidity of pneumonia and the proportion of deaths in hemo-dialysis patients with COVID-19 were higher,and some clinical symptoms lasted for a longer time than the general population.During the infection period,the incidence of dialysis-related complications in-creased,hemoglobin and nutritional status decreased.Elderly patients and patients with low albumin level had a higher risk of developing pneumonia after infection.
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Objective:To explore the application process, efficacy and safety of MR-guided radiotherapy based on MR-linac in esophageal cancer.Methods:The clinical data of patients with esophageal cancer treated with MR-linac at Shandong Cancer Hospital and Institute from September 2021 to July 2022 were retrospectively analyzed, to investigate the treatment process of esophageal cancer with MR-linac, and to analyze the efficacy and safety of patients. All patients received MR-guided radiotherapy, underwent CT and MR localization, target area delineation, and design of the Monaco treatment planning system plan. Adaptation-to-position adjustment was conducted during the pre-treatment evaluation. The median number of fractions was 25, the median single dose of planning target volume was 1.8 Gy, and the median total dose was 50.2 Gy. Median follow-up was 16 months.Results:Among the 12 patients in the whole group, there were 1 case of cervical esophageal cancer, 3 cases of upper thoracic esophageal cancer, 4 cases of middle thoracic esophageal cancer and 4 cases of lower thoracic esophageal cancer, including 3 cases of neoadjuvant radiotherapy and 9 cases of radical radiotherapy. All patients had a smooth treatment process. The median treatment time was 33 min, and the patients had good compliance. For patients with radical radiotherapy, one month after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 9; six months after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 6. All patients treated with neoadjuvant radiotherapy underwent surgery within 2 months, and one patient achieved pathological complete remission. The most common acute adverse reactions were radiation esophagitis (7 cases) and leukopenia in bone marrow suppression (8 cases), with late-stage adverse reactions being radiation pneumonia (1 case). The adverse reactions to radiotherapy were slight, and no grade 4 or above adverse reactions were observed.Conclusion:The clinical treatment process for esophageal cancer under MR-guided radiotherapy based on MR-linac is feasible, with good curative effects and mild adverse reactions.
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Objective To observe the clinical efficacy of FANG's scalp acupuncture combined with timing auricular point pressing therapy in the treatment of insomnia patients with maintenance hemodialysis(MHD).Methods A total of 70 patients with insomnia on MHD were randomly divided into observation group and control group,with 35 patients in each group.Both groups were given conventional treatment,the control group was given oral use of Estazolam Tablets on the basis of conventional treatment,and the observation group was given FANG's scalp acupuncture combined with timing auricular point pressing therapy.Both groups were treated for a total of 4 weeks of treatment.After 1 month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Pittsburgh Sleep Quality Index(PSQI)score and the Kidney Disease Quality of Life Short Form(KDQOL-SF)score,as well as the scores of the Hamilton Depression Scale(HAMD)and the Hamilton Anxiety Scale(HAMA),were observed in the patients of the two groups before and after treatment.The changes in hemoglobin(Hb),serum creatinine(Scr),and blood urea nitrogen(BUN)levels were compared before and after treatment between the two groups,and the safety of the two groups was evaluated.Results(1)After treatment,the PSQI and KDQOL-SF scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI and KDQOL-SF scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the HAMD and HAMA scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving HAMD and HAMA scores,and the differences were statistically significant(P＜0.05).(3)After treatment,the Hb,Scr,BUN levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving Hb,Scr,BUN levels,and the differences were all statistically significant(P＜0.05).(4)The total effective rate was 77.14%(27/35)in the observation group and 62.86%(22/35)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(5)Comparison of the incidence of adverse reactions in the two groups of patients,the difference was not statistically significant(P＞0.05).Conclusion FANG's scalp acupuncture combined with timing auricular point pressing therapy in the treatment of insomnia patients with MHD can effectively improve the sleep quality of patients and alleviate anxiety and depression,so as to improve the quality of life of patients,with remarkable efficacy.
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Objective To evaluate the value of magnetic resonance imaging(MRI)in prenatal diagnosis of fetal Chiari malformation.Methods The prenatal MRI findings of 27 cases of Chiari malformation confirmed by follow-up in Obstetrics and Gynecology Hospital,Fudan University from Feb 2010 to Feb 2022 were retrospectively analyzed and compared with ultrasound findings.Results Twenty-seven pregnant women,aged from 16-36 years(average 28.0 years)and 27 fetuses with gestation from 15.3-38.4 weeks(average 24.3 weeks)were studied.There were 18 cases of Chiari Ⅱ(Chiari malformation type Ⅱ,CMⅡ),3 cases of Chiari Ⅲ(CMⅢ),6 cases of Chiari Ⅳ(CMⅣ).CMⅡ and CMⅢ images showed brain herniation,descending pons,narrowing or disappearance of the posterior fossa cistern and the fourth ventricle,the subarachnoid space disappears.There were 17 cases of hydrocephalus,2 cases of cerebrospinal fluid loss,17 cases of"lemon head"and"banana cerebellar"signs,4 cases of encephalocele,15 cases of spinal bifida,3 cases of lower spinal cord and 2 cases of spinal cavity,4 cases of spinal angular deformity and 6 cases of other malformations.In CMⅣ,there were 2 cases of undeveloped cerebellum and 4 cases of cerebellum and brainstem dysplasia,hydrocephalus in 5 cases,posterior fossa cistern widening in 4 cases,and other malformations in 4 cases.MRI showed the posterior fossa structure and spinal cord more clearly than ultrasound,and could find lesions not detected by ultrasound.Conclusion Prenatal MRI can be used as a complementary examination of ultrasound,which can improve the accuracy of diagnosis of Chiari malformation,reduce the rate of missed diagnosis,and clarify the classification of Chiari malformation.
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Objective To explore the role of endothelial cells in angiogenesis and myocardial remodeling in heart failure based on MAPKs pathway mediated by tumor endothelial marker 1(TEM1).Methods Sixty-four mice were equally randomized into four groups:sham operation,myocardial infarction(MI),MI+sh-NC and MI+ sh-TEM1.On the 7th day after MI,the changes of EndMT in the infarct border area were detected by immunofluo-rescence staining,and the cardiac function of mice was evaluated by echocardiography on the 28th day.Mouse aortic endothelial cells(MAECs)were divided into three groups:control,Vector and rTEM1.In addition,MAECs were pretreated with MAPK inhibitor SB203580,and the cells were treated with rTEM1 for 48 h.The changes of EndMT and MAPKs signaling pathways in endothelial cells were evaluated by Western blot.Results In the myocardium at the border of infarction,the level of TEM1-1 increased slightly on the 1st day after MI,reached the peak on the 7th day,and then decreased on the 28th day.Compared with Vector group,the expression of VE-Cadherin protein in the rTEM1 group decreased significantly(P<0.05),and the levels of α-SMA and vimentin,relative migration distance,the number of invading cells,and the number of branching formation increased signifi-cantly(P<0.05).SB203580 reversed these changes of MAECs induced by rTEM1.Compared with the MI group,the co-staining level of CD31+Vimentin+ in the MI+sh-TEM1 group decreased significantly(P<0.01).On the 28th day,the LVEF and LVFS in the MI+sh-TEM1 group were significantly higher than those in MI group(P<0.05).Compared with the MI group,the expressions of p-P38/P38 and p-JNK/JNK in the endothelial cells of the MI+sh-TEM1 group decreased.Conclusion EndMT and angiogenesis induced by TEM1 participate in the pathogenesis of cardiac fibroblasts induced by MI,which may be mechanically related to the activation of MAPKs signaling pathway.
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Immunotherapy has entered the clinical treatment for various tumors, among which the blockade therapy of PD-1/PD-L1 immune checkpoint is currently the most important tumor immunotherapy method. At present, immunohistochemical method are used in clinical practice to detect PD-L1 expression in tumor patients and screen for indications. However, this method is constrained by factors such as heterogeneity, dynamic changes in PD-L1 expression, and limited sample collection. PD-(L)1 PET imaging utilizes radiolabeled molecules to non-invasively assess PD-(L)1 expression in space and time, and complementary use with IHC has theoretically incomparable advantages. This article reviews the latest progress in the PD-(L)1 probe molecular imaging principles, clinical research and existing problems.
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Objective:To analyze the expression and prognosis of B-cell lymphoma 7 protein family member A (BCL7A) in hepatocellular carcinoma, as well as the effect and mechanism of BCL7A expression on the invasion and migration of hepatocellular carcinoma cells.Methods:The cancer tissues and adjacent tissues of 40 patients with hepatocellular carcinoma who underwent radical hepatobiliary resection in the Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University from November 2017 to March 2018 were prospectively collected for protein extraction, including 29 males and 11 females, aged (58.5±10.4) years. The information of 374 cases of hepatocellular carcinoma and 50 cases of adjacent tissues were downloaded from The Cancer Genome Atlas (TCGA) database, and the hepatocellular carcinoma cell lines Hep3B and SMMC-7721 were transfected with overexpressing BCL7A plasmid and empty vector plasmid (negative control), respectively. Western blotting and immunohistochemistry were used to detect the expression of BCL7A, and Western blotting was also used to detect the expression of proteins related to epithelial-mesenchymal transition (N-cadherin, E-cadherin, snail). Transwell and cell scratch assays were used to detect cell invasion and migration.Results:Compared with adjacent tissues, the mRNA expression of BCL7A in 50 patients with hepatocellular carcinoma in TCGA was significantly increased ( t=13.38, P<0.001). According to the median mRNA expression level of BCL7A, 374 patients were divided into BCL7A high expression group ( n=187) and low expression group ( n=187), and the cumulative survival rate of BCL7A high expression patients was lower than that of low expression group, and the difference was statistically significant ( χ2=6.95, P=0.009). Western blot was used to detect the relative expression of BCL7A protein in cancer tissues, and found it was higher compared to adjacent tissues. Compared with the negative control group, the number of cells invaded by the BCL7A overexpression group of hepatoma cells Hep3B and SMMC-7721 was more than the negative control group respectively, (153.7±1.3) vs (63.7±4.7) and (307.7±25.14) vs (72.3±12.5), and the differences were statistically significant ( t=7.97, 8.38, both P=0.001) .The results of the cell scratch assay were consistent with the results of the Transwell invasion assay. The expressions of N-cadherin and snail in the BCL7A overexpression group were higher than those in the negative control group, and the E-cadherin was lower, and the difference was statistically significant (all P<0.05). Conclusions:The expression of BCL7A in cancer tissues of patients with hepatocellular carcinoma is elevated and is associated with poor prognosis. BCL7A may promote hepatocellular carcinoma cell metastasis and invasion by promoting epithelial-mesenchymal transition.
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Objective:To construct a column-line diagram diagnostic model based on serum and joint fluid inflammatory markers for the diagnosis of periprosthetic joint infections (PJI) after joint arthroplasty and to validate its predictive ability.Methods:The clinical data of 181 patients diagnosed with PJI or aseptic loosening in the Department of Orthopedics of the First Affiliated Hospital of Chongqing Medical University from January 2015 to June 2020 were retrospectively collected as a modeling group. The best indicators for diagnosing PJI were screened by lasso regression, single-factor and multifactor analysis. By comprehensively considering the weights and intrinsic connections of the indicators, a column-line diagram diagnostic model was constructed and used to develop a clinical decision support system (CDSS). Prospectively, the clinical data of patients diagnosed with PJI or aseptic loosening in the Department of Orthopedics of the First Hospital of Chongqing Medical University from July 2020 to December 2022 were collected as a validation group, and the diagnostic performance of the column-line diagram model was externally validated by methods such as receiver operating characteristic curve (ROC).Results:There were 85 cases of PJI in the 181 cases modeling group and 23 cases of PJI in the 49 cases validation group. Among the 27 potential factors analyzed by lasso regression analysis, body mass index (BMI), blood tests including platelet (PLT), absolute lymphocyte value, interferon γ (IFN-γ), ESR, IL-6, C-reactive protein, D-dimer, and joint fluid tests including C-reactive protein, IL-1, IL-4, IL-6, percentage of multinucleated neutrophils (PMN%), and CD64 may be potential indicators for the diagnosis of PJI. Univariate found significant differences between hematologic tests including sedimentation, C-reactive protein, IL-6, D-dimer and joint fluid tests including C-reactive protein, joint fluid CD64 index, C-reactive protein, IL-1, IL-4, IL-6, PMN%( P<0.05). Further multifactorial regression analysis screened serum IL-6, D-dimer, joint fluid CD64 index, C-reactive protein, IL-1, IL-4, IL-6, and percentage of multinucleated neutrophils, and based on that, the column-line graph model and CDSS system were constructed. The area under the ROC in the validation group was 0.978, and the AUC in the internal validation was 0.995; the C-index of the calibration curve was 99.50%, and the C-index of the internal validation was 99.53%, suggesting that the column-line diagram model has a good predictive ability. Conclusions:The column-line diagram for diagnosing PJI based on multiple diagnostic indicators showed good diagnostic performance. The CDSS system constructed by column-line diagrams could assist clinicians in diagnosing PJI and making reasonable strategies in time.
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Immunoassays are widely used in medicine, food, environment and other fields due to having the advantages of simpleness, rapidness and accuracy. Combining immunoassays with nanomaterials can improve the performance of immunoassays. Compared with traditional nanomaterials, upconversion nanoparticles (UCNPs) have excellent optical properties such as good photostability, long luminescence lifetime and narrow and tunable emission bands, which can significantly reduce background noise and improve analytical sensitivity when combined with immunoassay. This paper briefly introduces the luminescence mechanism of UCNPs, summarizes the synthesis and surface modification methods of UCNPs. And then 5 UCNPs-based immunoassay techniques, namely, fluorescence resonance energy transfer, inner filter effect, magnetic separation technique, upconversion-linked immunosorbent assay and upconversion immunochromatography, are discussed in detail. These sensing protocols of UCNPs-based immunoassays have been successfully utilized to detect various targets, including small molecules, macromolecules, and pathogens, all of which closely related to food safety, human health, and environmental pollution. Finally, the challenges and prospects of this technique are summarized and prospected. Although the UCNPs immunoassays based on antibodies and antigens have made great progress, most of the research is still in the stage of laboratory, and there is a long way to go to realize its social applications. There is a series of challenges need to be overcome. (1) Designing excellent water soluble and dispersive upconversion nanomaterials is needed. Hydrophilic ligands are bound to smaller upconversion nanoparticles and removing hydrophobic surface ligands are the most widely used methods to improve solubility and dispersity. (2) Multi-detection technology platforms and multi-mode simultaneous detection platforms have great potential, which will improve the efficiency of point of care detection. (3) The researchers also need to focus on some important problems. For examples, the upconversion luminescence efficiency of UCNPs is difficult to maintain, the synthesis method is complex, and the surface modification degree and functionalization are difficult to control.
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Background/Aims@#Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. @*Methods@#We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. @*Results@#The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. @*Conclusions@#Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.
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Objective To assess the causal relationship between coffee intake and prostate cancer risk by using the two-sample Mendel randomization (MR) method. Methods The genome-wide association study (GWAS) data on coffee intake (exposure) and prostate cancer (outcome) were obtained from two independent data sets in UK Biobank. The inverse variance weighted method (IVW), weighted median estimator method (WME), and MR-Egger method were used for MR analyses. The OR value and 95%CI were used to represent the association between coffee intake and prostate cancer. In addition, the MR-Egger method was performed for pleiotropic and heterogeneity tests, and the leave-one-out method was used for sensitivity analysis. Results A total of 38 SNP were selected as instrumental variables. The IVW method showed that coffee intake might reduce the risk of prostate cancer (OR=0.994; 95%CI: 0.990-0.999; P=0.009). The WME method obtained the same conclusions (OR=0.991; 95%CI: 0.985-0.999; P=0.018), but MR-Egger regression did not find a causal relationship between coffee intake and prostate cancer (OR=0.992; 95%CI: 0.983-1.000; P=0.084). The MR-Egger method showed no pleiotropy (intercept=4.2E-5; P=0.581) or heterogeneity (Q=27.20; P=0.854) among the instrumental variables. The sensitivity analysis indicated that the conclusion was robust. Conclusion Two-sample Mendel randomization analysis reveals that coffee consumption might reduce the risk of prostate cancer.
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BACKGROUND@#There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden.@*METHODS@#Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status.@*RESULTS@#A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status.@*CONCLUSIONS@#Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
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Femenino , Humanos , Persona de Mediana Edad , Masculino , China/epidemiología , Ciudades , Frío , Calor , Mortalidad , Temperatura , Factores de TiempoRESUMEN
At present, the major public health challenges caused by novel coronavirus infection have gradually subside. However, a large number of people are still suffering from long-novel coronavirus syndrome or post-novel coronavirus syndrome. The clinical manifestations of long coronavirus syndrome are related to multiple systems, such as respiratory, circulatory, nervous, digestive and musculoskeletal systems, with various long-term persistent symptoms after novel coronavirus infection. At the same time, the infection of the novel coronavirus is an important cause of frailty and sarcopenia in the elderly population. However, at present, the scholars have not paid enough attention to the skeletal muscle weakness caused by the novel coronavirus. Therefore, this paper focuses on the long-novel coronavirus syndrome and sarcopenia to explore the pathological mechanism of skeletal muscle attenuation caused by the SARS-CoV-2 mediated "cytokine storm", mitochondrial damage, hypoxia state and other links, so as to raise the attention of clinical and academic researchers and improve the clinical strategy of frailty and sarcopenia after novel coronavirus infection.
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The main clinical research advances of critical care in 2023 includes: new trials of Chinese herbal medicine, hydroxocobalamin (vitamin B12), methylene blue as well glucocorticoids have shown the potential to improve outcomes of patients with sepsis and septic shock; international committees launched new global definition and managing recommendations for acute respiratory distress syndrome (ARDS). Besides, a cluster of new evidences has emerged in many aspects as following: fluid control strategy in sepsis (restrictive/liberative), antibiotic infusion strategy (continuous/intermittent), oxygen-saturation targets for mechanical ventilation (conservative/liberative), blood pressure targets after resuscitation from out-of-hospital cardiac arrest (hypotension/hypertension), blood pressure targets after successful stroke thrombectomy (intensive/conventional), and nutritional support strategies (low protein-calories/conventional protein-calories, fasting/persistent feeding before extubation). Thus, given above progress, carrying out high -quality domestic multi-center clinical registration researches, constructing shareable standardized databases, as well raising public awareness of sepsis, should be the essential steps to improve our level of intensive care medicine.
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ObjectiveTo analyze the correlation between 11 small molecule active components and 1 protein component of characteristic processed products with porcine cardiac blood and other products of Salviae Miltiorrhizae Radix et Rhizoma（SMRR） from Menghe medical school and anti-cerebral ischemic oxidative damage， and to identify its key component markers of characteristic processed products with porcine cardiac blood for anti-cerebral ischemic oxidative damage. MethodHigh performance liquid chromatography（HPLC） was established to simultaneously determine the contents of 11 active ingredients in SMRR and its processed products［processed with porcine cardiac blood， porcine blood， wine and transferrin（Tf） in porcine cardiac blood］， and the content of Tf in different processed products of SMRR was detected by enzyme-linked immunosorbent assay（ELISA）. Furthermore， A zebrafish ischemic stroke model was constructed to evaluate the effects of different processed products of SMRR on the behavioral trajectory of cerebral ischemic zebrafish， the neuronal damage of transgenic zebrafish Tg（elavl3：eGFP） brain， as well as the levels of malondialdehyde（MDA） and superoxide dismutase（SOD） in the brain tissues. The hippocampal neurons oxygen-glucose deprivation/reoxygenation（OGD/R）-induced ischemia-hypoxia model was constructed to evaluate the effects of different processed products of SMRR on oxidative damage of neuronal cells by taking lactate dehydrogenase（LDH）， reactive oxygen species（ROS）， MDA and SOD as indexes. Finally， principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and Spearman correlation analysis were used to analyze the 11 small molecule active components and 1 protein component with efficacy indicators， in order to screen the key components of the characteristic processed products with porcine cardiac blood for cerebral ischemic oxidative damage. ResultCompared with the raw products， the contents of water-soluble and fat-soluble components in processed products of SMRR increased to different degrees， while the content of salvianolic acid A decreased. Compared with the wine-processed products， the contents of salvianolic acid B， danshensu， rosmarinic acid and other components in the porcine cardiac blood-processed products， porcine blood-processed products， Tf-processed products were increased， while the content of salvianolic acid A was decreased. ELISA results showed that there was no significant difference in Tf content between the porcine cardiac blood-processed products， porcine blood-processed products， Tf-processed products. Pharmacological results showed that different processed products of SMRR could improve the behavioral deficits， brain neuronal injury and oxidative stress after ischemic stroke in zebrafish， and the effect of the porcine cardiac blood-processed products was most pronounced. PCA results showed that salvianolic acid B， salvianolic acid A， rosmarinic acid， lithospermic acid， danshensu， tanshinone ⅡA， caffeic acid， cryptotanshinone and tanshinone Ⅰ were the main contributing components of SMRR and its processed products. And the results of correlation analysis showed that the contents of cryptotanshinone， rosmarinic acid， caffeic acid， dihydrotanshinone Ⅰ， salvianolic acid B， tanshinone ⅡA and tanshinone Ⅰ were negatively correlated with MDA level in zebrafish brain tissue， while the contents of lithospermic acid， protocatechuic aldehyde， rosmarinic acid， dihydrotanshinone Ⅰ， salvianolic acid B and Tf were positively correlated with SOD level， and the contents of rosmarinic acid， caffeic acid， dihydrotanshinone Ⅰ， salvianolic acid B， tanshinone ⅡA， tanshinone Ⅰ， danshensu， Tf were positively correlated with neuronal fluorescence intensity in the zebrafish brain. And the contents of lithospermic acid， protocatechuic aldehyde， rosmarinic acid， dihydrotanshinone Ⅰ， salvianolic acid B， tanshinone ⅡA and Tf were negatively correlated with LDH， ROS and MDA levels and positively correlated with SOD level. ConclusionThere are differences in the anti-ischemic oxidative damage effects of SMRR and its different processed products， among which the porcine cardiac blood-processed products has the strongest effect on improving oxidative damage， which may be related to the content changes of salvianolic acid B， danshensu， rosmarinic acid and other components. This study can provide a basis for clarifying the quality markers of SMRR processed with porcine cardiac blood for cerebral ischemia and elucidating its processing mechanism.
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@#Objective To investigate the expression of centromere protein U(CENPU)in the intestinal tissues of patients with colon cancer,and to analyze the effect of CENPU expression level on the prognosis of patients with colon cancer combined with bioinformatics.Methods Firstly,the expression of CENPU in cancer tissues and normal tissues of colon cancer patients was analyzed by the expression of CENPU in tissues was further verified by real-time quantitative real time polymerase chain reaction(qRT-PCR),Western blot(WB)and immunohistochemistry(IHC).Combined with clinical data,univariate and multivariate Cox regression are used to analyze the correlation between CENPU expression and clinical case parameters of colon cancer patients.Then,the predictive effect of CENPU expression on the prognosis of colon cancer patients are explored by drawing receiver operating characteristic(ROC)curve and Kaplan-Meier survival curve.Finally,the possible molecular mechanism of the effect of CENPU expression on the progression of colon cancer are analyzed by bioinformatics.Results By qRT-PCR,WB and IHC experiments,we find that compared with normal tissues,the expression of CENPU in cancer tissues of colon cancer patients is significantly increased.Cox regression analysis show that the expression of CENPU is significantly correlated with the age and TNM stage of patients,and is a risk factor affecting the prognosis of patients.Kaplan-Meier survival curve analysis show that colon cancer patients with high CENPU expression has significantly lower survival rates.ROC curve show that the model based on CENPU expression has a high predictive power for the prognosis of colon cancer patients area under the curve(AUC=0.832).Bioinformatics analysis show that CENPI,CENPN,CENPD,CENPK,CENPP,CENPM,CENPQ,CENPH,NDC80 and ITGB3BP have significant interaction with CENPU gene.CENPU is involved in DNA repair,MYC/TARGETS/V1 and PI3K/AKT/MTOR signaling pathways.Conclusion High expression of CENPU in cancer tissues of patients with colon cancer is significantly associated with poor prognosis of patients,suggesting that CENPU is expected to be a potential target for early diagnosis and prognosis prediction of patients with colon cancer.