[Clinical features and prognostic analysis of checkpoint inhibitor pneumonitis in patients with non-small cell lung cancer].

Objective: To describe the clinical characteristics of patients with non-small cell lung cancer (NSCLC) who developed checkpoint inhibitor pneumonitis (CIP) and to explore potential prognostic factors. Methods: NSCLC patients who were complicated with CIP after immune checkpoint inhibitors (ICIs) therapy in our institute were enrolled in this study from 1 July 2018 to 30 November 2022. Clinical data of NSCLC-CIP patients were collected, including clinical and radiological features and their outcomes. Results: Among the 70 enrolled NSCLC-CIP patients, there were 57 males (81%) and 13 females (19%). The mean age at the diagnosis of CIP was (65.2±6.3) years. There were 46 smokers (66%), 26 patients (37%) with emphysema, 19 patients (27%) with previous interstitial lung disease, and 26 patients (37%) with a history of thoracic radiation. The mean interval from the first application of checkpoint inhibitor to the onset of CIP was (122.7±106.9) days (range: 2-458 days). The main chest CT manifestations were coincided with non-specific interstitial pneumonia (NSIP) pattern and organizing pneumonia (OP) pattern. Most patients had grade 2 (21 cases) or grade 3 (34 cases) CIP. Seventeen patients had been concurrent with other immune-related adverse events such as rash, hepatitis, colitis, and thyroiditis. Half of the enrolled patients (36 patients/51%) had fever, and most patients had elevated C-reactive protein (52 patients/72%) and all patients had elevated erythrocyte sedimentation rate (70 patients/100%). Serum lactate dehydrogenase was elevated in 34 CIP patients. Prednisone≥1 mg·kg-1·d-1 (or equivalent) was the most commonly used initial treatment in CIP patients (50 patients/71.4%). Complications with pulmonary infections (OR=4.44, P=0.03), use of anti-fungal drugs (OR=5.10, P=0.03) or therapeutic dose of sulfamethoxazole (OR=4.86, P=0.04), longer duration of prednisone≥1 mg·kg-1·d-1 (or equivalent) (Z=-2.33, P=0.02) were probable potential risk factors for poor prognosis. Conclusions: Older males with smoking history might be predisposed to develop NSCLC-CIPs after ICIs therapy. NSIP pattern and OP pattern were common chest CT manifestations. Complications with pulmonary infections (especially fungal infection or Pneumocystis jirovecii pneumonia), longer duration, longer duration of high-dose corticosteroids were likely potential risk factors for poor prognosis.

[Whole-course management strategies for gastroesophageal reflux disease: an evidence mapping study based on clinical practice guidelines].

Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases with high incidence, complicated clinical symptoms, difficulties in standard treatment, and heavy medical burden. At present, some GERD-relevant clinical practice guidelines (CPGs) have been issued by different countries and academic organizations, but some recommendations were inconsistent, which has caused some problems for the current clinical whole-course management of GERD. To summarize the relevant evidence among the CPGs on GERD and formulate the whole- course management strategies, we included GERD-relevant CPGs published or updated after 2010 by searching websites of guidelines, relevant professional societies, and electronic databases. We extracted the recommendations and summarized the evidence from the aspects of symptoms, epidemiology, diagnosis and treatment, which was presented in the form of evidence mapping. We included 24 CPGs, including three in Chinese and 21 in English. The clinical practice management strategies of GERD were formulated based on the evidence from the aspects of clinical symptoms, diagnostic methods, medical treatment, anti-reflux surgery and endoscopic treatment, psychological treatment, and traditional Chinese medicine treatment.

Nomograms for predicting survival in patients with gastric carcinoid or neuroendocrine carcinoma based on the SEER database.

OBJECTIVE: The aim of this study was to construct a competent model that can effectively predict the prognosis of patients with gastric carcinoid (GC) or neuroendocrine carcinoma (NEC). PATIENTS AND METHODS: Data of patients with GC or NEC were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017. Univariable and multivariable Cox analysis was used to determine the independent factors for patients with GC or NEC. Nomograms were established based on the independent factors and the results were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: A total of 214 patients with GC and 65 patients with gastric NEC were extracted from the SEER database. Independent prognostic factors for patients with GC were M stage, gender, age, and chemotherapy. Independent prognostic factors for patients with gastric NEC included age, M stage, and chemotherapy. ROC curves, calibration curves, and DCA confirmed that the nomograms can precisely predict the prognosis of patients with GC and NEC. CONCLUSIONS: The nomograms can effectively predict survival in patients with GC or NEC, which may assist the clinician in their decision-making and quantitatively judge the prognosis of individual patients.

[Retrospective analysis and a cross-sectional questionnaire survey of lung cancer concomitant with interstitial lung disease].

Objective: To describe the clinical characteristics and prognosis of lung cancer concomitant with interstitial lung disease (LC-ILD), and to understand the current status of knowledge of LC-ILD by physicians in the departments related to the treatment of the disease. Methods: We conducted a retrospective analysis of in-hospitalized pathology identified lung cancer (LC) patients who were admitted to our hospital between January 2014 and December 2018. After reviewing their chest CT imagings and pathological reports, 70 patients who were concomitant with interstitial lung disease (ILD) were enrolled in our study. On the other hand, a cross-sectional survey using an online questionnaire was conducted in LC-ILD management doctors who came from 29 provincial hospitals. The perceptions of demographic features, LC characteristics and management, ILD characteristics and management, and the prognosis of LC-ILD were investigated. Results: Among the 70 enrolled LC-ILD cases, there were 52 males, and the mean age was (64.3±7.63) years (ranged from 49 years to 84 years). There were 51 patients who were older than 59 years. The most common pathological pattern of LC was adenocarcinoma. Most of them were diagnosed with LC and ILD simultaneously, and they were usually treated with chemotherapy while unresectable. There were 11 patients (15.7%) with positive EGFR or ALK mutation. Forty-five patients (64.3%) died during the follow-up, and 33 were died from LC progression. There were no significant differences between the surgical group and non-surgical group on age, pathological patterns, EGFR or ALK mutation. However, LC-ILD patients in the surgical group were diagnosed with earlier TNM classification and with better prognosis. A total of 1 014 doctors answered the questionnaire completely. In the feedback, patients aged 60 years and older (785 doctors/77.4%), and male patients (720 doctors/71%) were the predominant LC-ILD patients. Adenocarcinoma (390 doctors/38.5%), adenocarcinoma or squamous-cell cancer (SCC) (182 doctors/17.9%), and SCC (151 doctors/14.9%) were considered as the common pathological patterns of LC-ILD patients. In most doctors' feedback, the EGFR or ALK mutation was not common for LC-ILD: low (646 doctors/63.7%) or hardly (306 doctors/30.5%) positive mutation. The diagnosis of ILD was earlier than LC (506 doctors/49.9%) or there was no identified precedence of LC and ILD diagnosis (208 doctors/20.5%). Most of the doctors (693 doctors/68.3%) agreed that the vital factor for surgery or not was the severity of ILD for LC-ILD patients. There were great divergences on the treatment protocol both for the advanced LC and ILD. The patients with LC-ILD were died mostly from LC progression and ILD exacerbation (542 doctors/53.5%), followed by ILD exacerbation (237 doctors/23.4%) or LC progression (226 doctors/22.3%). Conclusions: The elderly male patients were predisposed to LC-ILD, and adenocarcinoma was the common pathological pattern. The LC-ILD patients with non-advanced LC who were performed with surgery had better prognosis. However, it is recommended to consider whether to perform surgery in combination with the severity of the ILD.

[Host factors and characteristics of hospitalized patients with pneumocystis jirovecii pneumonia].

Objectives: To describe the underlying diseases, microbiologic examination and severity of hospitalized patients with Pneumocystis jirovecii pneumonia (PJP) in a tertiary Chinese hospital. Methods: We conducted a retrospective analysis of 485 identified PJP patients who were admitted to our hospital between January 2013 and December 2021. Results: Among the 485 enrolled PJP cases, there were 237 males and 248 females, aging (53.3±16.2) years (range from 14 y to 88 y). They were divided into 8 subgroups with variable underlying diseases. There were 209 cases with connective tissue diseases(CTD), 27 cases with non-hematologic malignancies, 38 cases with hematologic malignancies, 81 cases with kidney diseases, 33 cases with idiopathic interstitial pneumonia(IIP), 30 cases infected with human immunodeficiency virus (HIV), and 42 cases with miscellaneous underlying diseases. In the CTD group, there was more females than males, while male patients were predominant in both the malignant and the HIV groups. The Pneumocystis was identified in 44.95%(218/485) sputum samples and 92.01%(265/288) bronchoscopic samples. Pneumocystis asci were observed at direct microscopic examination with Grocott's methenamine silver stain in 4.95%(24/485)sputum samples and 9.72%(28/288)bronchoscopic samples. Pneumocystis DNA fragments were identified by PCR analysis in 43.09%(209/485)sputum samples and 90.63%(261/288)bronchoscopic samples. Among the 8 groups, cytomegaviremia and respiratory failure were most common in the HIV-infected PJP group, but the rates of mechanic ventilation, intensive care unit (ICU) admission and death were the lowest. There were less PJP patients in the IIP group (IIP-PJP) who received mechanic ventilation and admitted to ICU than the other groups except HIV-infected PJP group. However, the mortality rate was highest for the IIP-PJP group. Conclusions: CTD was the most common predisposed underlying disease for our enrolled PJP cases. Cytomegaviremia and respiratory failure were common in HIV-infected PJP patients, but the prognosis of HIV-PJP was slightly better than the others. The disease was more severe, rapidly progressive and fatal in the IIP-PJP group.

[Clinical analysis of autoimmune diseases associated with interstitial lung diseases initially presented with idiopathic pulmonary fibrosis].

Objectives: To describe the clinical characteristics of patients with autoimmune diseases associated interstitial lung diseases (AID-ILD) initially presented with idiopathic pulmonary fibrosis (IPF) in a tertiary Chinese hospital. Methods: We conducted a retrospective analysis of 14 patients diagnosed with AID-ILD during the IPF follow-up between January 2016 and December 2021. Among the 14 enrolled AID-ILD cases, there were 13 males and 1 female, (69.71±9.07) years old (range from 55 y to 87 y). Results: Detailed clinical consultation and further laboratory analysis were performed during the follow-up when the IPF patients showed exaggerated dyspnea (7 cases), fever of unknown causes (6 cases), microscopic hematuria (5 cases), arthralgia and swelling (4 cases), arthralgia (2 cases), morning stiffness (2 cases) and renal failure (2 cases). Finally, 6 patients showed positive MPO-ANCA, one patient showed positive PR3-ANCA and 7 patients showed positive anti-CCP. During the IPF periods, 7 patients had received antifibrotic agents and 5 patients had been prescribed with N-acetylcysteine, and 1 patient had received antifibrotic agents after N-acetylcysteine. Among them, no medication was prescribed for one IPF patient. After they were diagnosed with AID-ILD, glucocorticoids and/or immunosuppressants were added for 13 of them. Thirteen of cases improved or stable after these treatments, but one didn't show significant changes. Conclusions: AID-UIP, especially ANCA-UIP, AAV-UIP or RA-UIP should be considered when the IPF patients showed fever of unknown origin, microscopic hematuria and/or arthritis related symptoms. They might benefit from the add-on glucocorticoids and/or immunosuppressants.

[Sorafenib regulates vascular endothelial growth factor by runt-related transcription factor-3 to inhibit angiogenesis in hepatocellular carcinoma].

Objective: To investigate the molecular mechanism of sorafenib against hepatocellular carcinoma. Methods: Sorafenib efficacy was screened and verified by the hepatocellular carcinoma patient-derived tumor xenograft (PDX) model. Veterinary B-mode ultrasonography and in vivo confocal laser scanning microscopy were used to observe PDX angiogenesis. Immunohistochemistry was used to observe the expression of proliferation and angiogenesis-related proteins in PDX tissue. Real-time quantitative PCR technology was used to observe the RUNX3 gene in PDX tissues. SPSS 17.0 statistical software was used for statistical analysis. Results: Four cases of PDX were used to screen the efficacy of sorafenib. PDX1 had a significant response to sorafenib, with an inhibition rate of 68.07%. Compared with the control group, sorafenib had significantly inhibited PDX1 relative tumor volume (5.76±2.14 vs. 11.71±2.87, P<0.05). Cell division index (39.50±7.72 vs. 67.10±9.14, P<0.05) and Ki67 expression (288.6±43.40 vs. 531.70±55.60, P<0.05) were significantly decreased. Veterinary B-mode ultrasonography showed evident blood flow signals in PDX1 tumors. In vivo confocal laser scanning microscopy results showed that sorafenib had significantly reduced the total vessel length (1573.00±236.21 vs. 2675.03±162.00, P<0.05) and area (11 145.33±1931.97 vs. 20 105.37±885.93, P<0.05)) of PDX1 tumors. Immunohistochemical results showed that sorafenib had significantly down-regulated the protein expressions of CD34 (27.55±3.76 vs. 45.47±5.57, P<0.05), VEGF (16.33±2.86 vs. 22.77±3.20, P<0.05) and MVD (38.75±6.01 vs. 55.50±8.61, P<0.05). Real-time PCR results showed that sorafenib had significantly up-regulated RUNX3 gene expression (2.14±0.71 vs. 1.00±0.36, P<0.05). However, there was a negative correlation between the expression of RUNX3 gene and the ratio of VEGF-positive cells in sorafenib group (R2=0.509 7). Conclusion: Sorafenib may inhibit the PDX angiogenesis and the growth of hepatocellular carcinoma by regulating the RUNX3-VEGF pathway.

[Status and influencing factors of knowledge awareness and service acceptance of HIV non-occupational post-exposure prophylaxis of men who have sex with men among college students among three cities of China, 2019].

Objective: To understand the knowledge awareness and service acceptance of HIV non-occupational post-exposure prophylaxis (nPEP) men who have sex with men (MSM) among college students in three cities of China. Methods: Male college students in 10 universities of Beijing, Shenzhen and Kunming aged 18 and above who had sex with men in the last 3 months were recruited as research objects by cluster stratified sampling from March 15, 2019 to April 14, 2019.Basic information, sexual behavior characteristics, knowledge, and service acceptance of nPEP were collected through online questionnaire survey. Multivariate dichotomy and unconditioned logistic regression model was used to explore related factors about knowledge awareness and service acceptance of nPEP. Results: A total of 293 MSM were surveyed. The average age was (21.0±0.2) years old, and 91.1% (267) were undergraduates. In the last 3 months before the survey, 54.3%(159) used condom each time of sex; 4.4%(13) had intercourse with the HIV infected men, and 9.2% (27)suffered STDs in the past 6 months. The 29.4% (86) had not received HIV testing in the past year. The nPEP knowledge awareness rate was 47.8% (140). The 21.2% (62) counseled nPEP services, and 9.9% (29) received nPEP services. After multiple logistic regression analysis, compared with those who not received HIV testing in the past year, OR (95%CI) value of those who received HIV testing for more than twice in the past year to aware the nPEP knowledge was 3.15 (1.01-9.86). Compared with those who not received HIV testing in the past year, OR (95%CI) value of those who received HIV testing for more than twice in the past year to counsel the nPEP services was 5.29 (1.51-18.51). Compared with those who never used rush in the last 3 months, OR(95%CI) value of those who ever used rush in the last 3 months to receive the nPEP services was 3.86 (0.99-14.98). Compared with those who not sexed with HIV infected in the last 3 months, OR (95%CI) value of those who sexed with HIV infected in the last 3 months to receive the nPEP services was 14.30 (3.35-61.03). Conclusion: The proportions of awareness of nPEP knowledge and acceptance of nPEP services are low. MSM among college students need further health education of the nPEP knowledge to improve the accessibility of services.

[Construction of apoptosis-stimulating of p53 protein 2 gene knockout mice and its effect on diethylnitrosamine-induced liver cancer].

Objective: To construct apoptosis-stimulating of p53 protein 2 (ASPP2) gene knockout mice using diethylnitrosamine (DEN)-induced liver cancer model to study the biological functions of ASPP2. Methods: The sgRNA oligonucleotides were constructed, and ASPP2 knockout mice were prepared with the CRISPR/Cas9 system. PCR and sequencing methods were used to identify the genotypes of F0 and F1 generations and their progeny. DEN was used to induce ASPP2+/- mice to establish liver cancer model. Results: PCR and sequencing results showed that ASPP2 gene was successfully knocked out in F0 generation mice. The genotype of F1 generation mice was accorded with ASPP2+/- and had obtained stable heredity. The success rate of DEN-induced liver cancer model (7/8 and 3 / 8) of ASPP2 + /-mice obtained by self-hybridization of F1 generation was significantly higher than that of wild-type mice. Conclusion: ASPP2 knockout mice were successfully constructed based on the CRISPR/Cas9 system. The success rate of DEN-induced liver cancer model of ASPP2 knockout mice was significantly higher than that of the wild-type mice.

[Surgical treatment of total subclavian artery occlusion: a single center experience of 67 cases].

Objective: To examine the outcomes of surgical repair for patients with total subclavian artery occlusion. Methods: A retrospective analysis was performed on 67 patients with subclavian artery occlusion disease admitted at Ward 1 of Aortic and Vascular Surgery Center, Fuwai Hospital from January 2016 to July 2019. The age was, and There were 51 male patients and 16 females with an age of (61.7±8.2) years (range: 37 to 79 years). The t-test, Mann-Whitney U-test, χ(2) test, and Fisher's exact test were used to analyze the factors related to the technique success. The Kaplan-Meier curve was used to calculate the cumulative patency rate and plot the corresponding survival curves, and the Log-rank test was used for comparison. The length from the subclavian artery ostial to the occlusion area was used as a variable to plot the receiver operating characteristic curve, and the optimal cut-off value was determined by the Youden index. Results: Eighteen patients received open surgery. Forty-nine patients with subclavian artery occlusion accepted endovascular repair, of which 38 patients succeeded (31 cases on left side and 3 cases on right side). Fifteen patients failed with endovascular therapy, of which 10 cases received elective surgery and 5 cases received conservative therapy. The success rate of endovascular repair was 69.4%(34/49). Among them, the success rate of left subclavian artery occlusion was 81.6%(31/38), while the right side was 3/11. Patients with the length from the subclavian artery ostial to the occlusion area ≥6 mm were more likely to get success (23/34 vs. 4/15, χ(2)=5.506, P=0.019). In the endo-group, one patient had hemorrhage in the left chest. In the open-group, one patient had lymphatic leakage. Follow-up period ranged from 3 to 46 months with a median of 22 months. The patency of endovascular repair group and the open surgery group was 92.6% and 90.8% at 12-month, while 82.9% and 84.3% at 24-month, respectively. The cumulative patency rates of smoking patients and non-smoking patients after endovascular treatment were 70.2% vs. 100% (P=0.048) at 24-month. No independent prognosis factors were identified through the Cox proportional risk model which significantly affected postoperative patency rates for patients with subclavian artery occlusion. Conclusions: Part of patients with subclavian artery occlusion can be treated by endovascular therapy. The success rate of left subclavian artery occlusions is higher than right sides. The length from the subclavian artery ostial to the occlusion area affected the success rate of repair.

[Prognostic value of Montreal Cognitive Assessment in heart failure patients].

Objective: To explore the occurrence of cognitive impairment in Chinese heart failure (HF) patients and it's impact on prognosis. Methods: In this prospective observational study, a total of 990 HF patients were enrolled from 24 hospitals in China during December 2012 to November 2014. All patients were administrated with the interview-format Montreal Cognitive Assessment (MoCA), according to which they were divided into MoCA<26 (with cognitive impairment) group and MoCA≥26 (without cognitive impairment) group. Baseline data were collected and a 1-year follow up was carried out. Univariate and multivariate logistic or Cox regression were performed for 1-year outcomes. Results: Cognitive impairment was evidenced in 628 patients (63.4%) and they were more likely to be older, female, and with higher proportion of New York Heart Association(NYHA) class Ⅲ-Ⅳ, chronic obstructive pulmonary disease (COPD), ischemic heart disease, while body mass index (BMI), education level, and medical insurance rate were lower (all P<0.05) as compared to patients in MoCA≥26 group. The rate of percutaneous intervention, device implantation, cardiac surgery and evidence-based medications were significantly lower in MoCA<26 group than in MoCA≥26 group (all P<0.05). During the 1-year follow up, patients in the MoCA<26 group had higher all-cause mortality (10.2%(64/628) vs. 2.2%(8/362), P<0.01), cardiovascular mortality (5.9%(37/628) vs. 0.8%(3/362), P<0.01) and major adverse cardiac and cerebrovascular events (MACCE) (9.6%(60/628) vs. 2.5%(8/362), P<0.01) than patients in the MoCA≥26 group. In univariate regression, MoCA<26 was associated with increased all-cause mortality (HR(95%CI):4.739(2.272-9.885), P<0.01), cardiovascular mortality (HR(95%CI):7.258(2.237-23.548), P=0.001) and MACCE (OR(95%CI):4.143(2.031-8.453), P<0.01). After adjustment by multivariate regression, MoCA<26 was indicated as an independent risk factor for all-cause mortality (HR(95%CI): 6.387(2.533-16.104), P<0.01), cardiovascular mortality (HR(95%CI): 10.848(2.586-45.506), P=0.001) and MACCE (OR(95%CI): 4.081(1.299-12.816), P=0.016), while not for re-hospitalization for HF (OR(95%CI):1.010(0.700-1.457), P=0.957). Conclusions: Cognitive impairment is common in HF patients,and it is an independent prognostic factor for 1-year outcomes. Routine cognitive function assessment and active intervention are thus recommended for HF patients.

Cepharanthine, a bisbenzylisoquinoline alkaloid, inhibits lipopolysaccharide-induced microglial activation.

Activation of microglial cells in the brain has been considered to be associated with various neurodegenerative diseases (NDD). In this study, cepharanthine, a bisbenzylisoquinoline alkaloid, was found to inhibit lipopolysaccharide (LPS)-induced microglial activation. Cepharanthine suppressed the release of nitric oxide (NO) by LPS-activated primary mouse cortical microglia and/or BV2 microglial cell line. Cepharanthine reduced LPS-induced mRNA expression of inducible NO synthase (iNOS), but it did not display direct NO-scavenging activity up to 100 µM in sodium nitroprusside (SNP) solution. Further studies revealed that cepharanthine suppressed the release of cytokines (TNF-α, IL-1ß, and IL-6) by LPS-activated microglial cells. Cepharanthine may have potential in the treatment of neurodegenerative diseases accompanied by microglial activation.

[Combined detection of KRAS, NRAS, BRAF and PIK3CA mutations in the plasma and tumor tissues of colorectal cancer patients].

Objective: To analyze the concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations detected in plasma and matched tumor tissues in colorectal cancer patients, in order to provide good evidences to support plasma could be a potential surrogate of tumor tissue for gene mutation test. Methods: One hundred and seventy-five cases of colorectal cancer were collected at the First Hospital of Jilin University, from October 2016 to October 2017.There were 101 males and 74 females, their ages ranged from 28 to 85 years,with median age of 59 years. The KRAS, NRAS, BRAF and PIK3CA gene mutations in the plasma and paired tumor specimens of all patients were detected by next generation sequencing. Results: The results of tissue samples test were gold standard. Comparison of the four genes showed that concordance rates between plasma and tissue samples were 81.1%(Kappa=0.543), 99.4%(Kappa=0.886), 99.4% (Kappa=0.886) and 97.7%(Kappa=0.714) respectively for KRAS, NRAS, BRAF and PIK3CA. The plasma detection rates of these genes were related to tumor stage(P=0.001), but not to gender(P=0.468) and age(P=1.000) of patients. Conclusions: The study shows a high concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations in plasma against mutation status in tumor tissue. In colorectal cancer, tumor tissue remains the best specimen for gene detection. However, patients from tumor tissue specimens cannot be obtained, especially those with advanced metastases, plasma can be used instead of tissue to detect the mutation status of KRAS, NRAS, BRAF and PIK3CA to guide targeted therapy.

Chronic obstructive pulmonary disease deaths, disability-adjusted life years, and risk factors in Hubei province of mid-China, 1990-2015: the Global Burden of Disease Study 2015.

OBJECTIVES: The trends of chronic obstructive pulmonary disease (COPD) mortality and prevalence from 1990 to 2015 in Hubei province of mid-China remain unknown. We used findings from the Global Burden of Disease (GBD) 2015 study to estimate the COPD burden and attributable to risk factors in Hubei province of China from 1990 to 2015. STUDY DESIGN: The GBD study uses various analytical tools and a diverse set of data sources to generate comparable estimates of deaths and mortality rates broken down by age, sex, cause, year, and geography. METHODS: Data were extracted from the GBD 2015 study. Statistical models were used to produce comprehensive results of COPD deaths, prevalence, disability-adjusted life years (DALYs), years of life lost, years lived with a disability, and attributable to risk factors in Hubei. The median of the percent change and 95% uncertainty intervals were determined for the period between 1990 and 2015. RESULTS: In 2015, there were 37,144 deaths from COPD in Hubei, accounting for 10.05% of the total deaths in Hubei. The age-standardized COPD death rate was reduced by 60.28% from 188.67 per 100,000 (in 1990) to 74.94 per 100,000 (in 2015). The age-standardized prevalence decreased from 4.30% (1990) to 2.85% (2015). By 2015, the leading risk factors for all ages COPD DALYs were smoking and ambient particulate matter pollution, accounting for 44.69% and 32.91%, respectively. The proportion of ambient ozone pollution was increasing steadily each year since 1990. CONCLUSION: Hubei has made substantial progress in reducing the mortality due to COPD since 1990, but the absolute number of COPD cases is increasing steadily, given the population growth and aging. The increasing contribution from smoking, ambient particulate matter pollution, and ambient ozone pollution should require growing attention.

[Effect of febuxostat on epithelial-to-mesenchymal transition of kidney tubules, serum interleukin-6 and transforming growth factor ß(1) in hyperuricemic rats].

Objective: To observe the effect of febuxostat on epithelial-to-mesenchymal transition (EMT) of kidney tubules and the levels of serum IL-6 nad transforming growth factor (TGF)ß(1) in hyperuricemic rats. Methods: Forty male SD rats were divided into 4 groups: normal control group (NC group), oteracil potassium group (OP group), oteracil potassium with febuxostat group (OF group) and oteracil potassium with benzbromarone group (OB group). Each group had 10 rats and balanced in body weights. To induce hyperuricemia, rats were given oteracil potassium by gastric gavage once a day for eight weeks. Rats in OF group and OB group were given either febuxostat or benbromarone starting with oteracil potassium, and rats in NC group was given saline only. Blood samples were taken before, and at the end of 4 and 8 weeks of the treatments and serum uric acid, creatinine, blood usea nitrogen(BUN), IL-6 and TGFß(1) contents were measured at each time point. Renal pathological changes were observed via HE and Masson staining, and the expression of α-SMA and E-cadherin were detected by immunohistochemistry. Results: Compared with those in NC group, the levels of serum uric acid, creatinine, BUN, IL-6 and TGFß(1) in the another three groups were increased significantly (all P<0.01). However, the IL-6 and TGFß(1) contents in OF group were much lower than those in OP group (P<0.01). HE and Masson staining showed that OF group had less damage and tubulointerstitial fibrosis than OP group and OB group (P<0.01). Moreover, the expression of α-SMA was significantly down-regulated (P<0.01) and that of E-cadherin was significantly up-regulated in OF group compared with those in OP group. Conclusion: Febuxostat treatment significantly inhibited EMT and reduced the levels of IL-6 and TGFß(1) in hyperuricemia rats.

Effects of reed straw, zeolite, and superphosphate amendments on ammonia and greenhouse gas emissions from stored duck manure.

Stored poultry manure can be a significant source of ammonia (NH) and greenhouse gases (GHGs), including nitrous oxide (NO), methane (CH), and carbon dioxide (CO) emissions. Amendments can be used to modify physiochemical properties of manure, thus having the potential to reduce gas emissions. Here, we lab-tested the single and combined effects of addition of reed straw, zeolite, and superphosphate on gas emissions from stored duck manure. We showed that, over a period of 46 d, cumulative NH emissions were reduced by 61 to 70% with superphosphate additions, whereas cumulative NO emissions were increased by up to 23% compared with the control treatment. Reed straw addition reduced cumulative NH, NO, and CH emissions relative to the control by 12, 27, and 47%, respectively, and zeolite addition reduced cumulative NH and NO emissions by 36 and 20%, respectively. Total GHG emissions (as CO-equivalents) were reduced by up to 27% with the additions of reed straw and/or zeolite. Our results indicate that reed straw or zeolite can be recommended as amendments to reduce GHG emissions from duck manure; however, superphosphate is more effective in reducing NH emissions.

The effectiveness of weekly iron supplementation regimen in improving the iron status of Chinese children and pregnant women.

It is evident that intermittent iron supplementation is better than daily supplementation in two aspects: iron absorption is more efficient and has insignificant side effects in contrast to the daily dose. The significantly higher daily iron loss observed in the daily iron supplemented groups rats also suggests alterations in total body iron metabolism. Based on serum ferritin distribution patterns, intermittent iron supplementation avoids temporary iron overload with daily iron supplemented. We conclude that weekly iron supplementation scheme is safer and easier to administer. This feasible strategy for the control of iron deficient anemia in pregnant women and children would be an effective iron-supplementation program (Baily et al., 1993).

PIP: Most governmental programs to control widespread iron deficiency in the developing world involve providing daily supplements of iron to all children and pregnant women. This approach has generally poor results due in part to dose-related undesirable gastrointestinal side effects and the lack of effective absorption and retention of iron consumed on a daily basis. However, recent evidence indicates that iron is absorbed significantly better when consumed only at intervals coinciding with gut mucosal renewals. That approach also prevents constant high iron concentrations in the gut which may cause undesirable side effects. Much lower iron doses administered intermittently are as effective in correcting iron nutrition and safer than daily doses in iron deficient anemic rats. 246 healthy 3-6 year olds and 405 pregnant women were enrolled in two studies to determine whether intermittent iron supplementation in humans is more efficient than daily iron administration. Weekly iron supplementation proved to be better than daily supplementation, producing more efficient iron absorption with fewer side effects. Serum ferritin distribution patterns indicate that intermittent iron supplementation avoids the iron overload which results from daily iron supplemented.