Network meta-analysis of combination strategies in metastatic hormone-sensitive prostate cancer.

ABSTRACT: This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer (mHSPC). PubMed, EMBASE, and the Cochrane Library were comprehensively searched for eligible randomized controlled trials (RCTs) published from inception to October 2023. Interventions included abiraterone, apalutamide, enzalutamide, docetaxel, darolutamide, and androgen deprivation therapy (ADT), either as doublet or triplet therapies. The outcomes examined were overall survival (OS), progression-free survival (PFS), castration-resistant prostate cancer (CRPC)-free survival, time to symptomatic skeletal event (SSE), and toxicity. The surface under the cumulative ranking curve (SUCRA) was determined to identify the preferred treatments. Ten RCTs were included. The combination of darolutamide, docetaxel, and ADT had the highest SUCRA of 84.3 for OS, followed by combined abiraterone, docetaxel, and ADT (SUCRA = 71.6). The highest SUCRAs for PFS were observed for triplet therapies (abiraterone, docetaxel, and ADT [SUCRA = 74.9], followed by enzalutamide, docetaxel, and ADT [SUCRA = 74.3]) and other androgen receptor axis-targeted therapy-based doublet therapies (SUCRAs: 26.5-59.3). Darolutamide, docetaxel, and ADT had the highest SUCRAs, i.e., 80.8 and 84.0 regarding CRPC-free survival and time to SSE, respectively. Regarding Grade >3 adverse events (AEs), the SUCRAs of triplet therapies (SUCRAs: 14.8-31.5) were similar to that of docetaxel and ADT (SUCRA = 39.5). Three studies had a low risk of bias in all categories; the remaining studies had at least an unclear risk of bias in at least one category. Triplet therapy demonstrated potentially enhanced effectiveness than doublet therapy in mHSPC, with acceptable safety concerns. Darolutamide might be the optimal option for triplet therapy in combination with docetaxel and ADT.

Effects of chronic restraint stress on the expression of N6-methyladenosine and related enzymes in the hippocampus of mice / 解剖学报

Objective To investigate the effect of chronic restraint stress on the expression of N6-methyladenosine (m6A)and related enzymes in the hippocampus of mice. Methods Twenty C57BL/6J male mice were randomly divided into control group and chronic restraint stress (CRS) group, the model group was given for 3 weeks chronic restraint stress to establish a mouse anxiety model. Open field test and elevated plus maze test were used to detect anxiety-like behavior; Immunohistochemistry and m6A RNA methylation assay were used to detect the expression changes of mouse hippocampal m6A; Western blotting and Real-time PCR were used to analyze hippocampal m6A related enzymes expression. Results 1.The behavioral results showed that, compared with the control group, the CRS group showed significantly reduced time spent in the center of the open field(P<0.01), the CRS group showed significantly reduced exploration time in the open arm of elevated plus maze (P<0.0001); 2. Immunohistochemical results showed that, compared with the control group, the hippocampal m6A content in the CRS group reduced significantly (P < 0.001); The results of the m6A RNA methylation assay showed that, compared with the control group, the CRS group showed significantly reduced amount of hippocampal m6A(P<0.05); 3. Real-time PCR results showed that the expression of hippocampal demethylase anaplastic lymphoma kinase B(AlkB) homolog 5(ALKBH5) (P<0.001) and fat mass and obestity associated protein(FTO) (P< 0.05) in the CRS group significantly up-regulated, the expression of methylase Wilms' tumour 1-associating protein (WTAP) (P<0.05) was significantly down-regulated compared with the control group; The expression of m6A methylation binding protein YTH domaincontaining family protein 3 (YTHDF3) (P < 0.05) and YTH domaincontaining protein 2 (YTHDC2) (P < 0.01) was significantly up-regulated. Western blotting result showed that, compared with the control group, the mouse hippocampal demethylase ALKBH5 (P < 0.05) and FTO (P < 0.05) expression in the CRS group significantly up-regulated, the expression of WTAP (P<0.01) was significantly down-regulated; m6A methylation binding protein YTHDF3 (P<0.01) and YTHDC2 (P<0.05) were significantly up-regulated. Conclusion In the anxiety model induced by chronic restraint stress, the expression of m6A in the hippocampus of mice is down-regulated. The mechanism may be related to the up-regulation of the m6A demethylase ALKBH5 and FTO or the down-regulation of the methylase WTAP.

The efficacy and safety of bamlanivimab treatment against COVID-19: A meta-analysis

BackgroundBamlanivimab is routinely used in the treatment of coronavirus disease 2019 (COVID-19) in worldwide. We performed a meta-analysis to investigate the efficacy and safety of bamlanivimab treatment in patients with COVID-19. MethodsWe searched articles from Web of Science, PubMed, Embase, the Cochrane Library and MedRxiv between 30 January 2020 and August 5, 2021. We selected randomized clinical trials (RCTs) and observational studies with a control group to assess the efficiency of bamlanivimab in treating patients with COVID-19. ResultsOur meta-analysis retrieved 3 RCTs and 7 cohort studies including 14461 patients. Bmlanivimab may help outpatients to prevent hospitalization or emergency department visit (RR 0.41 95%CI 0.29 to 0.58), reduce ICU admission (RR 0.47 95%CI 0.23 to 0.92) and mortality (RR 0.32 95%CI 0.13 to 0.77) from the disease. The combination of bamlanivimab and etesevimab may had a greater potential for positive treatment outcome. ConclusionBamlanivimab has demonstrated clinical efficacy on mild or moderate ill patients with COVID-19 to prevent hospitalization, reduce severity and mortality from the disease. Combinations of two or more monoclonal antibody increase the effect. Well-designed clinical trials to identify the clinical and biochemical characteristics in COVID-19 patients population that could benefit from bamlanivimab are warranted in the future. Key pointsO_ST_ABSQuestionC_ST_ABSCan bamlanivimab treat COVID-19 patients? What are the factors that have great impact on the treatment outcome? FindingsIn this meta-analysis that retrieved 3 RCTs and 7 cohort studies and included 14461 adults, Bmlanivimab may help outpatients to prevent hospitalization or emergency department visit (RR 0.41 95%CI 0.29 to 0.58), reduce ICU admission (RR 0.47 95%CI 0.23 to 0.92) and mortality (RR 0.32 95%CI 0.13 to 0.77) from the disease. MeaningIn COVID-19 pandemic, the use of bamlanivimab may be warranted. Combinations of two or more monoclonal antibody increase the effect.

Spontaneous remission of follicular bronchiolitis with nonspecific interstitial pneumonia: A case report and literature review / 北京大学学报(医学版)

A 41-year-old female patient was admitted in Department of Respiratory and Critical Care Medicine, Peking University Third Hospital because of having cough for a year. Multiple subpleural ground grass and solid nodules could be seen on her CT scan. Four months before admission, she began to experience dry mouth and eyes, blurred vision, finger joints pain, muscle pain and weakness in both lower limbs and weight loss. At the time of admission, the patient's vital signs were normal, no skin rash was seen, breath sounds in both lungs were clear, no rales or wheeze, no deformities in her hands, no redness, swelling, or tenderness in the joints. There was no edema in both lower limbs. Some lab examinations were performed. Tumor markers including squamous cell carcinoma (SCC) antigen, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), Cyfra21-1, pro-gastrin-releasing peptide (proGRP), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) were all normal. The antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, anti-dsDNA antibody, anti-Sm antibody, anti-SSA/SSB antibody, anti-ribonucleoprotein (RNP) antibody, anti-Jo-1 antibody, anti-SCL-70 antibody and anti-ribosomal antibody were all negative. The blood IgG level was normal. The blood fungal β-1.3-D glucose, aspergillus galactomannan antigen, sputum bacterial and fungal culture, and sputum smear test for acid-fast staining were all negative. Lung function was normal. Bronchoscopy showed the airways and mucosa were normal. To clarify the diagnosis, she underwent thoracoscopic lung biopsy, the histopathology revealed follicular bronchiolitis (FB) with nonspecific interstitial pneumonia (NSIP). She did not receive any treatment and after 7 months, the lung opacities were spontaneously resolved. After 7 years of follow-up, the opacities in her lung did not relapse. To improve the understanding of FB, a literature research was performed with "follicular bronchiolitis" as the key word in Wanfang, PubMed and Ovid Database. The time interval was from January 2000 to December 2018. Relative articles were retrieved and clinical treatments and prognosis of FB were analyzed. Eighteen articles concerning FB with complete records were included in the literature review. A total of 51 adult patients with FB were reported, including 18 primary FB and 33 secondary FB, and autoimmune disease was the most common underlying cause. Forty-one (80.4%) patients were prescribed with corticosteroids and/or immunosuppressive agents, 6 (11.8%) patients were treated with anti-infective, 5 (9.8%) patients did not receive any treatment. The longest follow-up period was 107 months. Among the 5 patients without any treatment, 1 patients died of metastatic melanoma, the lung opacities were unchanged in 1 patient and getting severe in 3 patients. In conclusion, FB is a rare disease, the treatment and prognosis are controversial. Corticosteroid and immunosuppressive agents could be effective. This case report suggests the possibility of spontaneous remission of FB.

Experimental study on the correlation between microcirculation and contrast-enhanced ultrasonography after crush injury of limbs / 中华超声影像学杂志

Objective:To explore the microcirculation formation mechanism of contrast-enhanced ultrasonography imaging performance in rabbits with limb muscle crush injury.Methods:Seventy-two New Zealand white rabbits were randomly divided into two groups. A limb muscle crush injury model was created by airing a balloon cuff device with a force of 40 kPa. Contrast-enhanced ultrasonography parameters were detected in the first group.In vivo microcirculation parameters were detected in the second group. Fine blood vessel diameter and blood flow velocity were calculated before extrusion and 0.5 h, 2 h, 6 h, 24 h, and 3 days after decompression.Results:Totally six animals died before the end of the experiment (3 rabbits in ultrasonic imaging and microcirculation detection groups, respectively). Compared with the uninjured muscle, the reperfusion of the injured muscle showed early and high enhancement in contrast-enhanced ultrasonography images. The peak intensity and area under the curve were significantly higher than those of the control subgroup at each time point after decompression(all P<0.05), and reached the peak at 24 h after decompression. The time-intensity curve showed a trend of rapid elevation and gradual drop. In the microcirculation group, compared with the control group, fine artery and vein diameters in the experimental group were wider and the blood flow velocity was slower, especially in the fine veins(all P<0.05). At each time point after decompression, there was a statistical difference between the control subgroup and the control subgroup, and the change reached the peak at 24 h after decompression. The blood flow state showed that the arterioles were dominated by linear flow and linear grain flow at each time point after decompression, and linear grain flow, grain flow and grain pendulum flow were observed in the fine veins. Blood flow stagnation and adhesion of white blood cells and white microthrombus were also observed in the fine veins. Correlation analysis showed that the peak intensity and area under the curve were positively correlated with the inner diameter of arterioles and veins( r=0.84, 0.94; r=0.85, 0.94; all P<0.05), and negatively correlated with the flow velocity of arterioles and veins( r=-0.94, -0.96; r=-0.93, -0.96; all P<0.05). Conclusions:In vivo microcirculation detection can reflect changes in muscle microvascular diameter and blood flow velocity, which have a correlation with quantitative ultrasound imaging parameters.

Prognostic value of primary tumor surgery in seminoma patients with distant metastasis at diagnosis: a population-based study.

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

A multicenter research on validation and improvement of the intelligent verification criteria for routine urinalysis / 中华检验医学杂志

Objective:A multi-center and large sample volume study was conducted on the verification and improvement of the early established criteria for intelligent routine urinalysis validation (including the microscopic review rules and manual validation rules, referred to as intelligent criteria for short), in order to improve the clinical application of this intelligent criteria.Methods:A total of 31 456 urine specimens were collected from the inpatients and outpatients in six hospitals in China, from March to September 2019. Firstly, 3105 specimens were analyzed for preliminary verification and improvement of the intelligent criteria based on the results of the microscopic examination and manual validation. Secondly, 28 351 specimens were used to verify the clinical application of the improved intelligent criteria. All samples were manually validated as reference.Results:The approval inconsistency rate of the manual validation rules in the original intelligent criteria was 8.59% (202/2 352), and the interception inconsistency rate was 8.84% (208/2 352). The false negative rate and the microscopic review rate of the microscopic review rules were similar to the previous results. Based on an in-depth analysis of big data and the discussions by senior technicians from eight hospitals, one microscopic review rules and four manual validation rules were added, meanwhile two manual validation rule was deleted. The manual validation standards were unified. Finally, the intelligent criteria was improved. Based on the improved intelligent criteria, for microscopic review rules, the false positive rate, false negative rate (misdiagnosis rate), and microscopic review rate did not change significantly, which were 14.72% (457/3 105), 4.06% (126/3 105), and 24.73% (768/3 105), respectively. The approval inconsistency rate and the interception inconsistency rate of manual validation rules were both reduced to 0; the total manual validation rate of the intelligent criteria was 50.89% (1 580/3 105), and the auto-validation rate was 49.11% (1 525/3 105). The large sample volume verification results were consistent with the preliminary verification results of the improved intelligent criteria.Conclusion:This multi-center and large sample volume study had shown that the improved intelligent criteria had better clinical performance.

Contribution of NOD2 signal pathway to Chlamydia pneumonia Cpn0423-induced inflammatory response / 中华微生物学和免疫学杂志

Objective:To understand and determine the biological properties of Chlamydia pneumonia (Cpn) hypothetical protein Cpn0423 and the mechanisms of which involved in Cpn0423-induced inflammatory response. Methods:The biological properties of Cpn0423 gene were analyzed using bioinformatic software. The subcellular localization of nucleotide-binding oligomerization domain-like receptor 2 (NOD2) in bone marrow-derived macrophages (BMDMs) was detected by confocal microscope. NOD2-siRNA was used to inhibit the expression of NOD2 at mRNA level. Cpn0423-induced macrophage inflammatory protein 2 (MIP-2) and IL-6 production in BMDMs were detected by ELISA. PCR was performed to detect Cpn0423 DNA in bronchoalveolar lavage fluid (BALF) of Cpn-positive patients.Results:The homology between Cpn0423 and other type Ⅲ secretion system effector proteins of Chlamydia ranged from 85% to 93%. NOD2-siRNA could effectively inhibit the expression of NOD2 at mRNA level in BMDMs ( P<0.001). Moreover, Cpn0423-induced production of MIP-2 [(920.5±99.1) pg/ml vs (130.1±11.5) pg/ml, P<0.001] and IL-6 [(266.2±58.4) pg/ml vs (165.7±21.5) pg/ml, P<0.001] in BMDMs were decreased following NOD2-siRNA pre-treatment. Cpn0423 DNA was detected in the BAlF of 83.3% (10/12) of Cpn-positive cases, but not in Cpn-negative cases. Conclusions:Cpn0423 induced inflammatory response in host cells through NOD2 pathway, which was closely related to the chronic inflammatory injury caused by Cpn.

Prognostic value of primary tumor surgery in seminoma patients with distant metastasis at diagnosis: a population-based study / 亚洲男科学杂志(英文版)

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

Performance and comparison of assessment models to predict 30-day mortality in patients with hospital-acquired pneumonia / 中华医学杂志(英文版)

BACKGROUND@#Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection in China with substantial morbidity and mortality. But no specific risk assessment model has been well validated in patients with HAP. The aim of this study was to investigate the published risk assessment models that could potentially be used to predict 30-day mortality in HAP patients in non-surgical departments.@*METHODS@#This study was a single-center, retrospective study. In total, 223 patients diagnosed with HAP from 2012 to 2017 were included in this study. Clinical and laboratory data during the initial 24 hours after HAP diagnosis were collected to calculate the pneumonia severity index (PSI); consciousness, urea nitrogen, respiratory rate, blood pressure, and age ≥65 years (CURB-65); Acute Physiology and Chronic Health Evaluation II (APACHE II); Sequential Organ Failure Assessment (SOFA); and Quick Sequential Organ Failure Assessment (qSOFA) scores. The discriminatory power was tested by constructing receiver operating characteristic (ROC) curves, and the areas under the curve (AUCs) were calculated.@*RESULTS@#The all-cause 30-day mortality rate was 18.4% (41/223). The PSI, CURB-65, SOFA, APACHE II, and qSOFA scores were significantly higher in non-survivors than in survivors (all P < 0.001). The discriminatory abilities of the APACHE II and SOFA scores were better than those of the CURB-65 and qSOFA scores (ROC AUC: APACHE II vs. CURB-65, 0.863 vs. 0.744, Z = 3.055, P = 0.002; APACHE II vs. qSOFA, 0.863 vs. 0.767, Z = 3.017, P = 0.003; SOFA vs. CURB-65, 0.856 vs. 0.744, Z = 2.589, P = 0.010; SOFA vs. qSOFA, 0.856 vs. 0.767, Z = 2.170, P = 0.030). The cut-off values we defined for the SOFA, APACHE II, and qSOFA scores were 4, 14, and 1.@*CONCLUSIONS@#These results suggest that the APACHE II and SOFA scores determined during the initial 24 h after HAP diagnosis may be useful for the prediction of 30-day mortality in HAP patients in non-surgical departments. The qSOFA score may be a simple tool that can be used to quickly identify severe infections.

Important Therapeutic Considerations in T1b Penile Cancer: Prognostic Significance and Adherence to Treatment Guidelines.

BACKGROUND: The clinical implications and contemporary management of T1b penile cancer are unknown. National treatment guidelines advocate surgical lymph node examination (SLNE) for T1b disease. OBJECTIVE: The aim of this study was to evaluate the prognosis of T1b disease and adherence to corresponding treatment guidelines. METHODS: We analyzed 296 patients from two academic centers, and 1263 patients from the Surveillance, Epidemiology, and End Results (SEER) registry (median follow-up 48.3 and 21 months, respectively). Multivariate Cox and Fine-Gray regressions were applied for penile cancer-specific survival (PCSS) analyses. RESULTS: In the academic center cohort, 28.3% of T1 patients had T1b disease, all of whom underwent SLNE. Nodal metastases were detected in 86.7% of T1b patients and 13.2% of T1a patients (p < 0.001). Using T1a as a reference, PCSS was significantly poorer in the T1b patients, with an adjusted hazard ratio (aHR) of 4.10 (p = 0.03). In the SEER cohort, 16.8% of T1 patients were classified as T1b. SLNE was performed in 21.7% of the T1b patients versus 38.2% of the T2 patients (p = 0.002). The probability of nodal metastases was 2.23-fold higher in T1b patients than in T1a patients (p < 0.001). In clinical N0M0 patients without SLNE, compared with T1a disease, T1b was associated with an aHR of 4.40 and a subdistribution HR of 4.53 for PCSS (both p = 0.003). CONCLUSIONS: T1b penile cancer is strongly associated with nodal metastases and adverse PCSS, and is poorly managed according to guidelines recommended in the nationwide registry.

Mechanism underlying the anti-apoptotic activity of pORF5 plasmid protein in Chlamydia trachomatis via high-mobility group box 1 protein: a preliminary study / 中华皮肤科杂志

Objective To explore the molecular mechanism underlying the anti-apoptotic activity of pORF5 plasmid protein of Chlamydia trachomatis,so as to provide an experimental basis for further clarifying the pathogenesis of Chlamydia trachomatis.Methods HeLa cells were divided into two groups:carbonyl cyanide m-chlorophenyl hydrazone (CCCP,an apoptosis inducer) group was stimulated by CCCP for 30 minutes,and pORF5 + CCCP group was pretreated with pORF5 plasmid protein for 18 hours followed by CCCP for 30 minutes.Then,Western blot analysis was performed to determine the expression of apoptosisrelated proteins Bcl-2,Bax and caspase-3,JC-1 fluorescent probe was used to detect changes in the mitochondrial membrane potential in HeLa cells,and cytochrome c release from mitochondria was analyzed by indirect immunofluorescence assay.To analyze whether high-mobility group box 1 (HMGB1) protein participated in the anti-apoptotic role of pORF5 plasmid protein,HMGB 1 shRNA and control RNA were separately transfected into the HeLa cells,which were then stimulated by pORF5 plasmid protein and CCCP.Then,the protein expression of Bcl-2,Bax,activated caspase-3 was determined,and cytochrome c release was analyzed.Data were compared between two groups by using paired t test.Results pORF5 plasmid protein could antagonize the CCCP-induced decrease of mitochondrial membrane potential,and the red/green fluorescence intensity ratio was significantly lower in the CCCP group (0.4 ± 0.1) than in the pORF5 + CCCP group (1.7 ± 0.3;t =6.95,P ＜ 0.01).The protein expression of Bcl-2 in the HeLa cells in the pORF5 + CCCP group was 5.3 ± 0.6 times more than that in the CCCP group (t =8.62,P ＜ 0.01),while the protein expression of Bax and activated caspase-3 in the pORF5 + CCCP group significantly decreased by 79％ ± 10％ (t =9.23,P ＜ 0.01) and 75％ ± 8％ (t =4.26,P ＜ 0.05) respectively compared with the CCCP group.Compared with the control RNA transfection group,the HMGB1 shRNA transfection group showed significantly decreased mitochondrial membrane potential in the HeLa cells (t =11.23,P ＜ 0.01),increased cytochrome c release,decreased Bcl-2 expresson (t =7.19,P ＜ 0.05) and increased Bax expression (t =13.06,P ＜ 0.01) after stimulation with pORF5 and CCCP.Conclusion Chlamydia trachomatis plasmid protein pORF5 plays an anti-apoptosis role by blocking the mitochondrial apoptotic pathway through HMGB1 protein.

Cardiovascular benefits of short-term indoor air filtration intervention in elderly living in Beijing: An extended analysis of BIAPSY study.

BACKGROUND: Adverse cardiovascular effects associated with air pollution exposure have been widely demonstrated. However, inconsistent cardiovascular responses were observed from reducing indoor air pollution exposure. We aimed to assess whether short-term air filtration intervention could benefit cardiovascular health in elderly living in high pollution area. METHODS: A randomized crossover intervention study of short-term indoor air filtration intervention on cardiovascular health was conducted among 35 non-smoking elderly participants living in Beijing in the winter of 2013, as part of Beijing Indoor Air Purifier StudY (BIAPSY). Portable air filtration units were randomly allocated to active filtration for 2 weeks and sham filtration for 2 weeks in the households. Twelve-hour daytime ambulatory heart rate variability (HRV) and blood pressure (ABP) were measured during active and sham filtration. Concurrently, real-time indoor and outdoor particulate matter with diameter less than 2.5 µm (PM2.5) and indoor black carbon (BC) concentrations were measured. We applied generalized additive mixed models to evaluate the associations of 1- to 10-h moving average (MA) exposures of indoor PM2.5 and BC with HRV and ABP indices, and to explore whether these associations could be modified by air filtration. RESULTS: We observed decreases of 34.8% in indoor PM2.5 and 35.3% in indoor BC concentrations during active filtration. Indoor PM2.5 and BC exposures were significantly associated with reduced HRV and increased ABP indices, and greater changes were observed during sham filtration. In specific, each 10 µg/m3 increase in indoor PM2.5 at MA8-h was associated with a significant reduction of 1.34% (95% CI: -2.42, -0.26) in SDNN during sham filtration, compared with a non-significant reduction of 0.81% (95% CI: -6.00, 4.68) during active filtration (Pinter< 0.001). Each 1 µg/m3 increase in indoor BC at MA8-h was associated with a significant increase of 2.41% (95% CI: 0.38, 4.47) in SBP during sham filtration, compared with a non-significant increase of -1.09% (95% CI: -4.06, 1.96) during active filtration (Pinter = 0.135). Nonlinear inverse exposure-response relationships of indoor air pollution exposures with predicted HRV and ABP indices also confirmed some cardiovascular benefits of short-term air filtration intervention. CONCLUSIONS: Our results suggested that short-term indoor air filtration intervention can be of some cardiovascular benefits in elderly living with high pollution episodes.

Nebulized Corticosteroids in the Treatment of COPD Exacerbations: Systematic Review, Meta-Analysis, and Clinical Perspective.

BACKGROUND: COPD guidelines report that systemic corticosteroids are preferred over inhaled corticosteroids in the treatment of exacerbations, but the inhaled route is considered to be an option. OBJECTIVES: To conduct a systematic review and meta-analysis regarding the efficacy and safety of inhaled corticosteroids for COPD exacerbations. The second objective was to provide pharmacologic and clinical perspectives of inhaled corticosteroids for COPD exacerbations. METHODS: The primary outcome was a change in FEV1 baseline versus the last measured value. Secondary outcomes were a change in (PaO2 ) and (PaCO2 ) baselines versus the last measured values; FEV1, PaO2 , and PaCO2 at 24 or 72 h; and hyperglycemia. RESULTS: Each of the 9 studies included in the meta-analysis was conducted in subjects who were hospitalized and not critically ill. Our meta-analysis indicated that high-dose nebulized budesonide 4-8 mg/d was noninferior to systemic corticosteroids on the change in FEV1 between baseline and the last measured value (mean difference of 0.05, 95% CI -0.01 to 0.12, P = .13) and PaCO2 (mean difference of -1.14, 95% CI -2.56 to 0.27, P = .11) but of inferior efficacy for PaO2 changes (mean difference of -1.46, 95% -2.75 to -0.16, P = .03). Hyperglycemia was less frequent with high-dose nebulized budesonide (risk ratio, 0.13; 95% CI 0.03-0.46; P = .002). CONCLUSIONS: Based on our meta-analysis with a change in FEV1 as the primary end point, high-dose nebulized budesonide was an acceptable alternative to systemic corticosteroids in hospitalized subjects with COPD exacerbations who were not critically ill. Additional well-designed prospective studies are needed in both the acute care and ambulatory settings. We provide perspective on how this evidence might be applied in clinical practice.

Clinical analysis of candidemia in immunocompetent patients / 北京大学学报(医学版)

OBJECTIVE@#To investigate the etiological and clinical characteristics of immunocompetent patients with candidemia.@*METHODS@#The clinical and microbiological data of patients diagnosed as candidemia admitted in Peking University Third Hospital from January 2010 to June 2016 were retrospectively analyzed. Underlying diseases, Candida spp. colonization, clinical manifestations, microbiological data, treatment and the outcome were compared between the HIV-negative immunocompromised (IC) and nonimmunocompromised (NIC) patients.@*RESULTS@#A total of 62 cases diagnosed as candidemia were analyzed including 36 men and 26 women, with 16 to 100 years of age [(66.02±17.65) years]. There were 30 NIC and 32 HIV-negative IC patients respectively. In the NIC patients, there were 19 cases (19/30, 63.33%) with admission in intensive care unit (ICU), 21 (21/30, 70.00%) associated diabetes mellitus or uncontrolled hyperglycemia and 22 (22/30,73.33%) receiving invasive mechanical ventilation, while in the HIV-negative IC patients, there were 8 (8/32, 25.00%), 13 (13/32, 40.63%) and 7 (7/32, 21.88%) respectively (P<0.05). The NIC patients had higher acute physiology and chronic health evaluation (APACHE II) scores and sequential organ failure assessment (SOFA) scores both at admission (19.98±5.81, 6.04±6.14) and candidemia onset (25.61±6.52, 12.75±8.42) than the HIV-negative IC patients (APACHEII 15.09±5.82, 22.15±5.98) and SOFA 2.87±2.73, 7.66±5.64 respectively (P<0.05). In the NIC patients, twenty-one cases (21/30, 70.00%) died in hospital, while 14 cases (14/32, 43.75%) in HIV-negative IC. The crude mortality was significantly different between the two groups (P<0.05). By blood culture, Canidia albicans remained the the most prevalent isolates in all the patients. Clinical manifestation, Candida spp. colonization, etiology and drug susceptibility were also similar between NIC and HIV-negative IC patients (P>0.05).@*CONCLUSION@#Candidemia in NIC patients tends to occur in those who are much more critically ill, more often admitted in ICU, and more frequently have diabetes mellitus or uncontrolled hyperglycemia and receive invasive mechanical ventilation than HIV-negative IC patients. NIC patients also have poorer prognosis than HIV-negative IC patients. Clinical manifestations, and microbiological characteristics are similar between HIV-negative IC and NIC patients.

Airway inflammation and small airway wall remodeling in neutrophilic asthma / 北京大学学报(医学版)

OBJECTIVE@#To investigate the distribution of airway inflammation phenotype in patients with bronchial asthma (asthma), and to analyze clinical characteristics, inflammatory cytokines, pulmonary small vessels remodeling and small airway wall remodeling in patients with neutrophilic asthma.@*METHODS@#Sixty-three patients with asthma were enrolled from January 2015 to December 2015 in Peking University Third Hospital. Clinical data including gender, age, body mass index (BMI), pulmonary function tests (PFTs), asthma control test (ACT) were recorded. All the patients underwent sputum induction. The cellular composition of the sputum was evaluatedand the concentration of active MMP-9 in the sputum tested. Blood routine tests were done and the concentration of IgE, periostin, and TGF-beta1 levels were measured in serum by enzyme-linked immunosorbent assay (ELISA). Small airway wall remodeling was measured in computed tomography (CT) scans, as the luminal diameter, luminal area, wall thickness and wall area % adjusted by body surface area (BSA) at the end of the 6th generation airway, in which the inner diameter was less than 2 mm. Small vascular alterations were measured by cross-sectional area (CSA), and the total vessel CSA < 5 mm2 was calculated using imaging software.@*RESULTS@#The distributions of airway inflammatory phenotypes of the asthmatic patients were as follows: neutrophilic asthma (34.9%, 22/63), eosinophilic asthma (34.9%, 22/63), mixed granulocytic asthma (23.8%, 15/63), and paucigranulocytic asthma (6.3%, 4/63). The neutrophilic subtype patients had a significantly higher active MMP-9 level in sputum compared with the eosinophilic phenotypepatuents, as 179.1 (74.3, 395.5) vs. 50.5 (9.7, 225.8), P<0.05. Sputum neutrophil count was negatively correlated with FEV1%pred (r=-0.304,P<0.05), and positively correlated with active MMP-9 level in sputum (r=-0.304, P<0.05), and positive correlation trend with airway wall thickness (r=0.533, P=0.06). There was a significantly negative correlation of active MMP-9 level in sputum with FEV1%pred (r=-0.281, P<0.05), in positive correlation with small airway wall area (%)(r=0.612, P<0.05), and inpositive correlation trend with airway wall thickness (r=0.612, P=0.06). Neutrophils count in peripheral blood was positively correlated with neutrophil counts in sputum.@*CONCLUSION@#Neutrophil count in airway is related to lung function in asthmatic patients. Neutrophils may accelerate small airway wall remodeling through the release of active MMP-9. Neutrophil count in peripheral blood is related to neutrophils count in sputum, which may be used as a substitute for evaluating inflammatory phenotype.

General and Specific Genetic Polymorphism of Cytokines-Related Gene in AITD.

Autoimmune thyroid disease (AITD) shows the highest incidence among organ-specific autoimmune diseases and is the most common thyroid disease in humans, including Graves' disease (GD) and Hashimoto's thyroiditis (HT). The susceptibility to autoimmune diseases is affected by increased autoantibody levels, susceptibility gene polymorphisms, environmental factors, and psychological factors, but the pathogenesis remains unclear. Various cytokines and related genes encoding them play important roles in the development and progression of AITD. CD152, an expression product of the CTLA-4 gene, downregulates T cell activation. The A/A genotype polymorphism in the CT60 locus may reduce the production of thyroid autoantibodies. The C1858T polymorphism of the PTNP22 gene reduces the expression of its encoded LYP, which increases the risk of GD and HT. GD is an organ-specific autoimmune disease involving increased secretion of thyroid hormone, whereas HT may be associated with the destruction of thyroid gland tissue and hypothyroidism. These two diseases exhibit similar pathogenesis but opposite trends in the clinical manifestations. In this review, we focus on the structure and function of these cytokines and related genes in AITD, as well as the association of polymorphisms with susceptibility to GD and HT, and attempt to describe their differences in pathogenesis and clinical manifestations.

Prevention of postpartum hemorrhage and diverticulum in scarred uterus with oxytocin and hemabate / 中国生化药物杂志

Objective To investigate the best application time and effect of the prevention and treatment of postpartum hemorrhage caused by uterine atony. Methods A total of 168 women with bleeding tendency were treated in our hospital from October 2014 to October 2016. They were randomly divided into three groups, 56 cases each. Among them, A group was used immediately after delivery, and group B was suffering from uterine atony, which was the use of hemabate, and C group did not use hemabate. The blood loss and the amount of postpartum hemorrhage in the three groups were compared and analyzed. Results Compared with group B and C, the amount of bleeding, the amount of bleeding in the 2 hours postpartum and the amount of 24 hours postpartum hemorrhage in group A were significantly lower than that in group(P<0.05). The 2 hours postpartum bleeding volume and 24 hours postpartum hemorrhage in group B were significantly lower than that in group C(P<0.05). The incidence of postpartum hemorrhage in group A was 3.57％, significantly lower than that in group B, group 14.28％ and group C, 30.36％(P<0.05). The incidence of postpartum hemorrhage in group B was 14.28％, significantly lower than that in group C (30.36％) (P<0.05). Conclusion To prevent and treat uterine atony postpartum hemorrhage, it is effective to prevent and treat postpartum hemorrhage. And the best application for the immediate use of fetal labor, can further reduce the amount of postpartum hemorrhage, to ensure maternal safety.

Effect of Shenqi Fuzheng injection combined with IFN-α on the expression of STAT1 gene in hepatocellular carcinoma cells / 中国现代普通外科进展

Objective:To study the effect of Shenqi Fuzheng injection combined with interferon-α (IFN-α) on the expression of STAT1 gene in hepatocellular carcinoma cells,and to elucidate its mechanism of IFN-α synergistic effect.Methords:The effect of IFN-α injection alone or combined with Shenqi Fuzheng injection on the proliferation of MHCC97-L cells was detected by MTT assay.IFN-α was detected by Real-time PCR and Western-blot respectively.The expression of STAT1 mRNA and protein in the experimental group,the negative control group (NaCl) and the blank control group were determined,and the effect of Shenqi Fuzheng injection on the transcription and expression of STAT1 was determined.The expression of STAT1 in lentiviral vector MTT assay was used to detect the effect of IFN-α alone or in combination with Shenqi Fuzheng injection on the STAT1 gene silencing cells.The expression of STAT1 was detected by RT-PCR and Western-Blot in MHCC97L cells.Strain,on cell proliferation.Results:Compared with IFN-α alone,Shenqi Fuzheng injection combined with IFN-α enhanced the inhibitory effect of IFN-α on MHCC97-L (P＜0.01) and up-regulated the expression of STAT1mRNA and protein (P＜0.05).Successfully constructed the STAT1 gene silent in the MHCC97-L cell line.There was no significant difference in the inhibition rate of MHCC97-L between Shenqi Fuzheng injection and IFN-α (P＞0.05).Conclusion Shenqi Fuzheng Injection can up-regulate the expression of STAT1 in human hepatocellular carcinoma cell line MHCC97-L,so as to increase the effect of IFN-α.

Association between Polymorphism of Endothelin Receptor Type A and Delayed Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage / 现代检验医学杂志

Objective To investigate the genetic association between endothelin receptor type A(EDNRA)gene polymor-phism and delayed cerebral vasospasm(DCVS)in patients with aneurysmal subarachnoid hemorrhage(aSAH).Methods 133 aSAH patients from January 2015 to January 2017 were recruited to participate in the study.According to whether com-bined with DCVS,they were divided into the DCVS group(78 cases)and the control group(55 cases).Genotype was deter-mined by polymerase chain reaction-restriction fragment length polymorphism combined with DNA direct sequencing tech-nique for the polymorphism of the EDNRA gene.Results Samples of DCVS group and control group both were consistent with Hardy-Weinberg's law of inheritance(χ2=0.295,P=0.863;χ2=0.652,P=0.722).There were significant differ-ences of EDNRA gene rs5335 polymorphism between DCVS group and control group,under allele model(χ2=4.213,P=0.040)and the dominant model(χ2=4.790,P=0.029).However,there was no difference of EDNRA gene polymorphism between DCVS group and control group under recessive model(χ2=1.299,P=0.254).Multivariate Logistic regression a-nalysis showed that allele C was protective factor of DCVS for aSAH patients(OR=0.572,95%CI 0.401~0.872,P=0.021).Conclusion For aSAH patients,EDNRA gene rs5335 polymorphism may closely related to DCVS.