[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.

[Clinical analysis of COVID-19 in patients with preexisting interstitial lung abnormalities].

Objective: To describe the clinical characteristics of SARS-CoV-2 infected patients with interstitial lung abnormalities (ILA) during the COVID-19 pandemic. Methods: We respectively enrolled ILA patients who had been regularly followed up in Peking Union Medical College Hospital for more than six months since January 2021. Clinical data of these ILA patients were collected after the outbreak of COVID-19 pandemic (from December 2022 to January 2023), thirty-eight patients with preexisting ILA were enrolled. Among them, there were 34 ILA patients (20 males and 14 females) who were infected with SARS-CoV-2 during this period, with an average age of (64.0±8.8) years old (range: 41-80). There were 12 (35.3%) ILA patients who were suffered from COVID-19(pneumonia group) and others were the non-pneumonia group. The clinical characteristics, including vaccination status, features of COVID-19 and outcomes of the two groups were compared. Results: Regarding the subcategories of ILA, there were 7 cases of subpleural fibrotic ILA, 10 cases of subpleural non-fibrotic ILA, and 17 cases of non-subpleural ILA. Before SARS-CoV-2 infection, the average pulse oxygen saturation at rest was (97.38±0.87)% (range: 96%-99%); average forced vital capacity (FVC) was (97.6±18.1)% predicted (range: 65%-132%); and average diffusion capacity for carbon monoxide (DLCO) was (76.2±16.3)% predicted (range: 53%-108%). Nineteen patients had been vaccinated with 3 doses of SARS-CoV-2 vaccines, and 5 of them developed COVID-19. One patient had received one dose of vaccine and did not develop COVID-19. The other 14 patients had not been vaccinated, and seven of them developed COVID-19. Of the 12 patients with COVID-19, six were diagnosed with severe COVID-19, and the other 6 ILA patients were diagnosed with moderate COVID-19. Among them, 1 patient was complicated by deep vein thrombosis of left lower limb. All 6 patients with severe COVID-19 who were cured after systemic corticosteroids. As for the other six moderate COVID-19 patients, all were cured and/or improved greatly: two were treated with short-term oral corticosteroids, one was prescribed a dose of compound betamethasone, and the other two were not treated with systemic corticosteroids. Conclusion: Patients with ILA were predisposed to develop COVID-19 after infection with SARS-CoV-2, and more than half of them had severe COVID-19.

[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.

[The role of the national oral health program in the development of oral health service and related thinkings].

Conception of public health was firstly put forward by American professor Winslow. Ensuring and promoting the health of general population is the key connotation for the definition of public health. Oral disease has become a public health problem. Caries which preventable and curable is the most common oral disease and the etiology is also clear. Oral health comprehensive intervention program for children in central and western regions was set up in 2008 by Chinese government. The program included sealing on the first permanent molar and oral health education towards primary school children covering mid-west area. This was the first oral health program invested by government and managed by Chinese Stomatological Association. Six years later, the program was popularized to the whole nation, and renamed as national oral health comprehensive intervention program for children in China. The program had made deep impact on development of oral health service in China. The study tries to analyze the challenges of oral health service through reviewing the background, content, organization and effectiveness of the program, aiming to provide suggestions on policy, financing, system, ability and technology for the future development.

[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.

[Preventive strategy of economy class syndrome].

Economy class syndrome (ECS) refers to a series of symptoms, such as lower limb swelling, chest pain, dyspnea, and sudden death, that occur during or after a long-distance flight. Its essence is venous thromboembolism. ECS, as a preventable syndrome, is one of the causes of sudden death in long-distance travelers. Medical assistance to the African region is a very important diplomatic matter of China. It often takes medical workers more than 10 hours of long-distance flight to reach the recipient country. Therefore, it is essential to improve the understanding of ECS and corresponding prevention strategies among the long-distance traveling people including medical workers assisting Africa, which could guarantee their health and ensure the smooth implementation of the work of assisting Africa.

[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.

[Establishment and consistency verification of the standard operation procedure for laboratory detection of immunoglobulin G oligoclonal bands in cerebrospinal fluid].

Objective: To establish the standard operation procedure (SOP) for detection of oligoclonal band (OCB) in cerebrospinal fluid (CSF) and verify consistency by using this SOP in different laboratories. Methods: The SOP for detection of CSF-OCB fluid was successfully established by an expert feedback approach. Neuroimmunology laboratories in 3 representative Chinese three-tier research hospitals were selected for this study, and commercially available protein electrophoresis automation systems and detection SOP were set up. The quality control product was provided by the College of American Pathologists (CAP) and Sebiacompany were used for interior quality and compared to each other, respectively. Seventeen serum and CSF paired samples were tested and compared using the same SOP. Kappa test or Kendall W test were adopted to evaluate the inter-laboratory consistency among different hospitals. Results: The results of repeated testings in a single hospital suggested that the 2-and 4-fold dilution for CSF-OCB were reported as positive, while 64-and 128-fold dilution were reported as negative. Positive or negative inconsistencies were reported in 8-, 16-, and 32-fold dilution. After increasing the number of repetitions, the results showed that both 16-and 32-fold dilution were reported as negative, and 8-fold dilution exhibited negative results (2 positive results for 40 repetitions, coincidence rate=95%).The results of multi-center inter-laboratory quality assessment showed that the detection consistency rate among 3 hospitals was 100% (Kappa value =1). Conclusions: The SOP to detect CSF-OCB established in this study demonstrates a good repeatability and stability. Therefore,such SOP would be a good reference for diagnostic laboratories to detect CSF-OCB in China.

Enhanced high temperature ferromagnetism in Bi1-x R x FeO3 (R = Dy, Y) compounds.

In this work we report experimental evidence for the weak high-temperature ferromagnetism in Bi1-x R x FeO3 (R = Dy, Y) compounds by systematic characterizations, excluding the possible side-effects from other iron-based impurities. Remarkable saturated magnetic moment was observed in the Y-substituted samples, Bi1-x Y x FeO3, which is larger than the moment obtained in Bi1-x Dy x FeO3, the Dy-substituted samples with antiferromagnetic background. The physical origin of the weak ferromagnetic transition is discussed and serious lattice distortions have been identified based on the x-ray diffraction and Raman scattering data, although the rhombohedral structure symmetry remains unchanged upon the substitutions. It is believed that the structural distortion suppressed cycloid spin structure is the main factor for the enhanced magnetization in Bi1-x R x FeO3 compounds. Additionally, the Dy3+-Fe3+ antiferromagnetic coupling, which strengthens the antiferromagnetic interaction in Bi1-x Dy x FeO3 compounds, acts as the driving force for the magnetic discrepancy between Bi1-x Y x FeO3 and Bi1-x Dy x FeO3 samples.

Ethnic Disparities in Dental Caries among Adolescents in China.

Comprehensive research on ethnic disparities in dental caries in China is limited. The aims of this cross-sectional study were to compare the levels of dental caries in adolescents between the Han ethnic group and ethnic minority groups in China and to explore the risk indicators for dental caries within ethnic subgroups. Data from the Fourth National Oral Health Survey in 2015, which covered all 31 province-level administrative divisions in mainland China, were used. The dental caries status in the permanent dentition of adolescents aged 12, 13, 14, and 15 y was measured using the decayed, missing, and filled teeth (DFMT) score, and sociodemographic characteristics and oral health-related behaviors were also collected. A total of 118,601 adolescents were included, with ethnic minority groups accounting for 13.15%. Of the Han and minority groups, the standardized prevalence of dental caries experience was 40.58% and 47.67%, and the mean DMFT scores were 0.97 and 1.28, respectively. According to the multivariate zero-inflated negative binomial regression analysis, the caries status of minorities was more severe than Han adolescents (adjusted prevalence rate ratio [PRR], 1.14; 95% confidence interval [CI], 1.10-1.18). This disparity was greater among adolescents who lived in rural areas, had mid-level economic status, and frequently consumed sugary beverages. After propensity score matchings, Uygur (PRR, 1.44; 95% CI, 1.25-1.67), Tibetan (PRR, 1.39; 95% CI, 1.3-1.48), and Yi (PRR, 1.24; 95% CI, 1.04-1.48) adolescents were significantly more likely to have caries than Han adolescents. Subgroup analyses revealed that gender, age, location of residence, economic status, region, consumption of sweet snacks and sugary beverages, and dental visit pattern were significantly associated with dental caries within ethnic minorities.

[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.

[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.

[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.

[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.

[Features of a modified WHO/UCLA AVLT performance in amnestic mild cognitive impairment and mild Alzheimer's disease].

Objective: To compare the features of a modified WHO/UCLA AVLT performance in the cognitive normal, amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (mild AD) patients. Method: A total of 105 cases of cognitivenormal (CN), 48 aMCI and 50 mild AD patients were included between 2016 and 2018. All subjects undertook detailed neuropsychological tests and brain MRI/CT scan. Results: The total score of five learning trials in CN, aMCI and AD groups were 53.9±6.9, 34.6±8.3 and 23.7±6.2, respectively (P<0.001). The score of 20-min delay recallwere 12.5±1.6, 4.3±3.0 and 0.6±1.0, respectively (P<0.001) in three groups. The score of cued recall were 13.0±1.4, 7.0±2.4 and 2.6±2.0, respectively (P<0.001). The score of 20-min delay recall had the largest effect sizes between CN and aMCI groups (Cohen'd=3.8, 95%CI,3.3-4.4), and CN and mild AD groups (Cohen'd=8.1, 95%CI 7.1-9.1). Cued recall had the largest effect size between aMCI and mild AD groups (Cohen'd=2.04, 95%CI 1.5-2.5). The scores of learning total score, 20-min delay recall, cued recall and recognition had the strong relationships with the scores of mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) , but obtaining moderate relationships with Boston naming test and trail making test (TMT) and weak relationships with digit span and figure copy. Age and education had no relationship with the main indices of this modified AVLT. Conclusions: The modified WHO/UCLA AVLT is still an age and education fair test to assess memory domain function. Qualitative analysis of AVLT profiles may be useful to differentiate the CN, aMCI and mild AD in Chinese sample.