[Exploratory analysis of gut microbiota differences in patients with bronchial asthma of different inflammatory types].

Objective: To observe the characteristics and differences of gut microbiota in asthma patients with different inflammatory types through metagenomic analysis. Methods: Adults aged ≥18 years who visited the Respiratory Clinic of Peking University Third Hospital from August 1, 2021 to August 31, 2022 and were primarily diagnosed with asthma were selected as the study subjects. Finally, 29 patients with stable asthma were included. Fresh fecal samples were collected and the fecal DNA was extracted for high-throughput 16sRNA sequencing of gut microbiota. The diversity and community structure of gut microbiota in different groups of asthma patients were compared, and the species differences were analyzed through random forest and LEfSe analysis. Results: There were sex-based differences in asthma patients with different types of inflammation, and the proportion of female patients was higher in neutrophilic asthma patients (χ2=4.14, P=0.042). There was no significant intergroup difference in the alpha diversity of gut microbiota among asthma patients with different inflammatory types, but there were significant differences in the microbiome. Patients with neutrophilic asthma had higher relative abundance of Bacillales (P=0.029) and Oscillospiraceae (P=0.015). In species LEfSe analysis, patients with eosinophilic asthma had a higher relative abundance of fungi. Conclusion: There are intergroup differences in the gut microbiota of asthma patients with different inflammation types, and fungi are biomarkers that distinguish the differences in gut microbiota between patients with eosinophilic asthma and neutrophilic asthma.

[EBF1 Promotes the Sensitivity of Cervical Cancer Cells to Cisplatin via Activating FBN1 Transcription].

Cisplatin (DDP) is widely used in the chemotherapy of cervical cancer (CC), the fourth most common female malignancy worldwide. However, some patients progress to chemotherapy resistance, which leads to chemotherapy failure, tumor recurrence, and poor prognosis. Therefore, strategies to identify the regulatory mechanisms underlying CC development and increase tumor sensitivity to DDP will help improve patient survival. This research was designed to ascertain the mechanism of EBF1-dependent regulation of FBN1 which promotes chemosensitivity of CC cells. The expression of EBF1 and FBN1 was measured in CC tissues resistant or sensitive to chemotherapy and in DDP-sensitive or -resistant cells (SiHa and SiHa-DDP cells). SiHa-DDP cells were transduced with lentiviruses encoding EBF1 or FBN1 to evaluate the influence of these two proteins on cell viability, expression of MDR1 and MRP1, and cell aggressiveness. Moreover, the interaction between EBF1 and FBN1 was predicted and demonstrated. Finally, to further verify the EBF1/FB1-dependent mechanism of DDP sensitivity regulation in CC cells a xenograft mouse model of CC was established using SiHa-DDP cells transduced with lentiviruses carrying EBF1 gene and shRNA directed to FBN1 EBF1 and FBN1 showed decreased expression in CC tissues and cells, particularly in those resistant to chemotherapy. Transduction of SiHa-DDP cells with lentiviruses encoding EBF1 or FBN1 lead to decreased viability, IC50, proliferation capacity, colony formation ability, aggressiveness, and increased cell apoptosis. We have shown that EBF1 activates FBN1 transcription by binding to FBN1 promoter region. Additionally, it was revealed that FBN1 silencing reversed the promoting effect of EBF1 overexpression on chemosensitivity of CC cells in vivo. EBF1 facilitated chemosensitivity in CC cells by activating FBN1 transcription.

[Recommendations for diagnosis and treatment of systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with complicated pathogenesis and diverse clinical manifestations. The current recommendations of the Chinese Rheumatology Association are based on a comprehensive investigation of evidence based medicine, domestic and international guidelines for SLE, and experts' proposals, and aim to provide a more scientific and authoritative reference for the diagnosis and management of SLE. The recommendations focus on four aspects; clinical manifestations, laboratory evaluation, diagnosis and disease assessment, and disease treatment and monitoring. The goal of the recommendations is to standardize the diagnosis and treatment of SLE in China so as to improve the prognosis of SLE patients.

[Spontaneous remission of follicular bronchiolitis with nonspecific interstitial pneumonia: A case report and literature review].

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 ß-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.

[Imaging phenotypes of chronic obstructive pulmonary disease based on biphasic quantitative CT features].

Quantitative analysis was performed on the biphasic CT of 40 patients [43-80 (66.1±9.0) years old, including 37 males] with stable chronic obstructive pulmonary disease (COPD) to measure the percentage of emphysema (Emph%); the percentage of small airway disease (SAD%) and the square root of the wall area of hypothetical airway with internal perimeter of 10 mm (Pi10). Based on the cluster analysis of Emph%, SAD% and Pi10, the patients were divided into five imaging phenotypes including no obvious imaging abnormality type (n=11), small airway disease-dominant type (n=9), bronchial wall thickening-dominant type (n=8), emphysema-dominant type (n=6) and mixed type (n=6). Patients with the same Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade had similar degree of airflow limitation, but the lesion components were not identical. Being different from the traditional imaging classification, even in the cases of mild emphysema, they can be further divided into small airway disease-dominant type and bronchial wall thickening-dominant type according to the difference of airway disease.

[Spatial and temporal distribution and predictive value of chest CT scoring in patients with COVID-19].

Objective: To explore a modified CT scoring system, its feasibility for disease severity evaluation and its predictive value in coronavirus disease 2019 (COVID-19) patients. Methods: This study was a multi-center retrospective cohort study. Patients confirmed with COVID-19 were recruited in three medical centers located in Beijing, Wuhan and Nanchang from January 27, 2020 to March 8, 2020. Demographics, clinical data, and CT images were collected. CT were analyzed by two emergency physicians of more than ten years' work experience independently through a modified scoring system. Final score was determined by average score from the two reviewers if consensus was not reached. The lung was divided into 6 zones (upper, middle, and lower on both sides) by the level of trachea carina and the level of lower pulmonary veins. The target lesion types included ground-glass opacity (GGO), consolidation, overall lung involvement, and crazy-paving pattern. Bronchiectasis, cavity, pleural effusion, etc., were not included in CT reading and analysis because of low incidence. The reviewers evaluated the extent of the targeted patterns (GGO, consolidation) and overall affected lung parenchyma for each zone, using Likert scale, ranging from 0-4 (0=absent; 1=1%-25%; 2=26%-50%; 3=51%-75%; 4=76%-100%). Thus, GGO score, consolidation score, and overall lung involvement score were sum of 6 zones ranging from 0-24. For crazy-paving pattern, it was only coded as absent or present (0 or 1) for each zone and therefore ranging from 0-6. Results: A total of 197 patients from 3 medical centers and 522 CT scans entered final analysis. The median age of the patients was 64 years, and 54.8% were male. There were 76(38.8%) patients had hypertension and 30(15.3%) patients had diabetes mellitus. There were 75 of the patients classified as moderate cases, as well as 95 severe cases and 27 critical cases. As initial symptom, dry cough occurred in 170 patients, 134 patients had fever, and 125 patients had dyspnea. Reparatory rate, oxygen saturation, lymphocyte count and CURB 65 score on admission day varied among patients with different disease severity scale. There were 50 of the patients suffered from deterioration during hospital stay. The median time consumed for each CT by clinicians was 86.5 seconds. Cronbach's alpha for GGO, consolidation, crazy-paving pattern, and overall lung involvement between two clinicians were 0.809, 0.712, 0.678, and 0.906, respectively, showing good or excellent inter-rater correlation. There were 193 (98.0%) patients had GGO, 147 (74.6%) had consolidation, and 126(64.0%) had crazy-paving pattern throughout clinical course. Bilateral lung involvement was observed in 183(92.9%) patients. Median time of interval for CT scan in our study was 7 days so that the whole clinical course was divided into stages by week for further analysis. From the second week on, the CT scores of various types of lesions in severe or critically patients were higher than those of moderate cases. After the fifth week, the course of disease entered the recovery period. The CT score of the upper lung zones was lower than that of other zones in moderate and severe cases. Similar distribution was not observed in critical patients. For moderate cases, the ground glass opacity score at the second week had predictive value for the escalation of the severity classification during hospitalization. The area under the receiver operating characteristic curve was 0.849, the best cut-off value was 5 points, with sensitivity of 84.2% and specificity of 75.0%. Conclusions: It is feasible for clinicians to use the modified semi-quantitative CT scoring system to evaluate patients with COVID-19. Severe/critical patients had higher scores for ground glass opacity, consolidation, crazy-paving pattern, and overall lung involvement than moderate cases. The ground glass opacity score in the second week had an optimal predictive value for escalation of disease severity during hospitalization in moderate patients on admission. The frequency of CT scan should be reduced after entering the recovery stage.

Sapphire advanced mitigation process: wet etch to expose sub-surface damage and increase laser damage resistance and mechanical strength.

A novel, to the best of our knowledge, method of wet chemical etching of sapphire workpieces (such as optics, wafers, windows, and cones), called the sapphire advanced mitigation process (or sapphire AMP), has been developed that exposes sub-surface mechanical damage created during the optical fabrication process and significantly enhances the surface laser damage resistance ($ \gt {2{\times}}$>2×) and mechanical strength (up to $\sim{2.6{\times}}$∼2.6×). Sapphire AMP involves first treating the workpiece with a mixture of sulfuric and phosphoric acid $([{\rm H_{2}{\rm SO_{4}}}]:[{\rm H_{3}{\rm PO_{4}}}]=1:3)$([H2SO4]:[H3PO4]=1:3) at 220°C, followed with phosphoric acid at 160°C, then with sodium hydroxide base (NaOH) and surfactant at 40°C, and finally with a high-pressure deionized water spray rinse. Sapphire AMP has been demonstrated on both A- and C-plane sapphire workpieces. The mechanism of this etch process involves the reaction of the sapphire $({\rm Al_{2}}{\rm O_{3}})$(Al2O3) surface with sulfuric acid $({\rm H_{2}}{\rm SO_{4}})$(H2SO4) forming aluminum sulfate $[{{\rm Al}_2}{({{\rm SO}_4})_3}]$[Al2(SO4)3], which has low solubility. The high phosphoric acid content in the first and second steps of sapphire AMP results in the efficient conversion of ${{\rm Al}_2}{({{\rm SO}_4})_3}$Al2(SO4)3 to aluminum phosphate $({\rm AlPO_{4}})$(AlPO4), which is very soluble, greatly reducing reaction product redeposition on the workpiece surface. Sapphire AMP is shown to expose sub-surface mechanical damage on the sapphire surface created during the grinding and polishing processes, whose etched morphology has either isotropic or anisotropic evolution depending on the nature of the initial surface damage. Sapphire AMP was also designed to remove the key known surface, laser absorbing precursors (namely, foreign chemical impurities, the fracture surface layer of preexisting sub-surface damage, and reaction product or foreign species redeposition or precipitation). Static and sliding indention induced surface microfractures on sapphire are shown after sapphire AMP to have a significant decrease in the fast photoluminescence intensity (a known metric for measuring the degree of laser damaging absorbing precursors). In addition, the onset of laser damage (at 351 nm 3 ns) on sapphire AMP treated workpieces was shown to increase in fluence from $\sim{4}$∼4 to $ \gt {9}.{5}\;{{\rm J/cm}^2}$>9.5J/cm2. Finally, biaxial ball-on-ring mechanical tests on sapphire disks showed an increase in the failure stress from 340 MPa (with pre-existing 28 µm flaws) to $\sim{900}\;{\rm MPa}$∼900MPa after sapphire AMP, which is attributed to the blunting of the surface microfractures.

[Severe acute respiratory syndrome coronavirus 2 infection in renal transplant recipients: A case report].

The novel coronavirus is a newly discovered pathogen in late December 2019, and its source is currently unknown, which can lead to asymptomatic infection, new coronavirus pneumonia or serious complications, such as acute respiratory failure. Corona virus disease 2019 (COVID-19) is a new type of respiratory disease that is currently spreading all over the world and caused by this coronavirus. Its common symptoms are highly similar to those of other viruses, such as fever, cough and dyspnea. There is currently no vaccine or treatment for COVID-19. Everyone is susceptible to infection with this disease, and owing to the long-term use of immunosuppressants, the immunity of kidney transplant recipients is suppressed, and it is more likely to be infected with the disease. At present, its impact on kidney transplant recipients is unclear. This article reports the clinical features and therapeutic course of novel coronavirus infection in a patient after renal transplantation. A 37-year-old female patient who received a kidney transplant 6 months before was diagnosed with novel coronavirus pneumonia. The patient's symptoms (such as fever, chills, dry cough, muscle aches), laboratory tests (such as decreased white blood cell count, elevated liver enzymes and D-dimer, positive viral nucleic acid test), and chest CT (multiple left lower lung plaque ground glass shadow) were similar to those of non-transplanted novel coronavirus pneumonia patients. In terms of treatment, because the immunity of kidney transplant recipients has been suppressed for a long time, it is a very common strategy to suspend the use of immunosuppressive agents. Therefore, the patient immediately discontinued the immunosuppressive agent after admission, so that she could restore immunity against infection in a short time. At the same time, the use of glucocorticoids was also very important. Its immunosuppressive and anti-inflammatory effects played a large role in the treatment process.In addition, prophylactic antibiotics was needed, and nephrotoxic drugs should be used with caution. Finally, following discounting the use of immunosuppressant and a low-dose glucocorticoid-based treatment regimen, COVID-19 in this renal transplant recipient was successfully cured. The cure of this case was of great significance, and this adjuvant nonspecific antiviral therapy could provide a template for the treatment of other such patients.

[Analysis of the correlation between lymphocyte subsets and severity of corona virus disease 19].

OBJECTIVE: To understand the differences in lymphocyte subsets in patients with different clinical classifications of corona virus disease 19 (COVID-19). METHODS: Eighty-one patients with COVID-19 who were admitted to the isolation ward under the responsibility of three medical aid teams in the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from February 8, 2020 to March 28, 2020, were selected to collect clinical data. According to the relevant diagnostic criteria, the disease status of the patients was classified into moderate cases (n=35), severe cases (n=39) and critical cases (n=7) when lymphocyte subset testing was performed. Their blood routine tests, lymphocyte subsets and other indicators were tested to compare whether there were differences in each indicator between the patients of different clinical classification groups. RESULTS: The differences in the absolute count of total lymphocytes, T-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and natural killer (NK) cells among the three groups of patients were all statistically significant (P < 0.05), and the critical cases were significantly lower than the moderate and severe cases in the above indicators, and the indicators showed a decreasing trend with the severity of the disease. In 22 patients, the six indicators of the absolute count of T-lymphocytes, B-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and NK cells, CD4+/CD8+ ratio were all within the normal reference range in the first test, and 59 patients had abnormalities of the above indicators, with the absolute count of NK cells and CD8+ T lymphocytes decreasing most frequently (61%, 56%). The patients with the absolute count of NK cells and CD8+ T lymphocytes below the normal reference range were one group, and the remaining abnormal patients were the other group. There were more critical cases in the former group (moderate : severe : critical cases were 4 : 8 : 7 vs. 19 : 21 : 0, respectively, P=0.001), and all the deaths were in this group (6 cases vs. 0 case, P=0.001). The absolute B lymphocyte count was below the normal reference range in 15 patients, and the remaining 64 cases were within the normal range. The ratio of moderate, severe and critical cases in the reduced group was 4 : 7 : 4, and the ratio of critical cases was more in normal group which was 30 : 31 : 3, and the difference between the two groups was statistically significant (P=0.043). CONCLUSION: The more critical the clinical subtype of patients with COVID-19, the lower the absolute count of each subset of lymphocytes.

[Detection and evaluation of SARS-CoV-2 nucleic acid contamination in corona virus disease 19 ward surroundings and the surface of medical staff's protective equipment].

OBJECTIVE: To determine the environmental contamination degree of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in corona virus disease 2019 (COVID-19) wards, to offer gui-dance for the infection control and to improve safety practices for medical staff, by sampling and detecting SARS-CoV-2 nucleic acid from the air of hospital wards, the high-frequency contact surfaces in the contaminated area and the surfaces of medical staff's protective equipment in a COVID-19 designated hospital in Wuhan, China. METHODS: From March 11 to March 19, 2020, we collected air samples from the clean area, the buffer room and the contaminated area respectively in the COVID-19 wards using a portable bioaerosol concentrator WA-15. And sterile premoistened swabs were used to sample the high-frequency contacted surfaces in the contaminated area and the surfaces of medical staff's protective equipment including outermost gloves, tracheotomy operator's positive pressure respiratory protective hood and isolation clothing. The SARS-CoV-2 nucleic acid of the samples were detected by real-time fluorescence quantitative PCR. During the isolation medical observation period, those medical staff who worked in the COVID-19 wards were detected for SARS-CoV-2 nucleic acid with oropharyngeal swabs, IgM and IgG antibody in the sera, and chest CT scans to confirm the infection status of COVID-19. RESULTS: No SARS-CoV-2 nucleic acid was detected in the tested samples, including the 90 air samples from the COVID-19 wards including clean area, buffer room and contaminated area, the 38 high-frequency contact surfaces samples of the contaminated area and 16 surface samples of medical staff's protective equipment including outermost gloves and isolation clothing. Moreover, detection of SARS-CoV-2 nucleic acid by oropharyngeal swabs and IgM, IgG antibodies in the sera of all the health-care workers who participated in the treatment for COVID-19 were all negative. Besides, no chest CT scan images of medical staff exhibited COVID-19 lung presentations. CONCLUSION: Good ventilation conditions, strict disinfection of environmental facilities in hospital wards, guidance for correct habits in patients, and strict hand hygiene during medical staff are important to reduce the formation of viral aerosols, cut down the aerosol load, and avoid cross-infection in isolation wards. In the face of infectious diseases that were not fully mastered but ma-naged as class A, it is safe for medical personnel to be equipped at a high level.

[Clinical value of extended radical resection for pT3 stage gallbladder cancer].

Objective: To investigate the clinical value of extended radical resection for stage pT3 gallbladder cancer (GBC). Methods: The clinical and pathological data of 323 patients with stage pT3 GBC who received regional radical resection or extended radical resection in 7 domestic hepatobiliary centers in China from January 2013 to December 2018 were retrospectively analyzed. The propensity score matching method was used to select 36 cases in each of the regional radical resection group (group A1) and the extended radical resection group (group B1). The surgical indicators and overall survival rates of the two groups were compared, and prognostic factors were analyzed. Results: The number of positive lymph nodes [2(0,3)] and the total number of lymph nodes removed [3(1,4)] in group B1 were both higher than those in group A1 [1(0,1), 4(2,7)] (all P<0.05). There was no significant difference in other clinical and pathological factors between the two groups (all P>0.05). The 1, 3, and 5-year survival rates of group A1 were 75%, 44%, and 29%, respectively, which were significantly higher than those of group B1 of 50%, 15%, and 11% (χ(2)=11.311, all P<0.001). Extensive radical resection (HR=2.161, 95%CI: 1.222-3.821), hepatic parenchymal invasion (HR=2.324, 95%CI: 1.305-4.139), positive lymph node rate ≥1/3 (HR=2.927, 95%CI: 1.641-5.220), and ⅢB/ⅣB staging (HR=3.325, 95%CI: 1.750-6.320) are risk factors for the prognosis of GBC patients (all P<0.05), of which extended radical resection (HR=1.969, 95%CI: 1.083-3.581) was an independent risk factor for prognosis (P<0.05). When the ratio of positive lymph nodes was<1/3 and the tumor invaded the hepatic parenchyma, the overall survival rate of group B1 was significantly lower than that of group A1 (all P<0.05). Conclusions: The overall survival rate in patients with stage pT3 GBC whose lymph node positive rate<1/3 and/or hepatic parenchymal invaded cannot be improved by extended radical resection. Extended radical resection is an independent risk factor for patient prognosis.

[Analysis of scoring system of twin pregnancy vaginal delivery].

Objective: To Analyze the prenatal factors and forecast the success rate of vaginal delivery of twin pregnancy. Methods: Totally, 114 cases of twin pregnant women who were under the systematic antenatal care and had deliveries in Beijing Obstetrics and Gynecology Hospital from January 2017 to March 2019 were collected. The inclusive criteria were uncomplicated twin pregnancy with head downward position of the first fetus, not monochorioallantoic twin twins, and the willingness for vaginal delivery. Two groups were classified based on their successful vaginal delivery. 96 cases in vaginal delivery group (study group) and 18 cases in the comparison groupwhich were transferred to Caesarean sections during trial delivery. The evaluated prenatal factors included: (1) Fetal factors: the chorionicity of the twin pregnancy, position of the second fetus, fetal weights and the weight difference of two fetuses. (2) Maternal factors:the maternal age, delivery gestational age, parity, body mass index (BMI), reasonability of weight gain during pregnancy, pregnancy complications, such as gestational diabetes mellitus (GDM), hypertensive disorder of pregnancy, and the application of assisted reproductive technology. (3) The technical title of the delivery doctor, modes of labour (spontaneous labor or induced labour and its mode) and the application of labor analgesia, etc. Single-factor logistic analysis and multiple-factor logistic regression were used to do statistical analysis and nomograms were plotted, finally receiver operating characteristic (ROC) curves and standard curves were formed for internal verifications and Youden index were utilized to determine the cut-off values. Results: Five variables:maternal age,complicated GDM, reasonability of weight gain during pregnancy, parity, and the weight of the second fetus is less than the firsthad obvious influence on the success rate of vaginal delivery in twin pregnancy. After quantifying the influence weight, the influence of each factor was as follows:the age of the mother <35 years old: 64; no GDM: 100, no insulin application in GDM: 47, and application of insulin: 0; reasonability of weight gain during pregnancy: 82; parity≥2: 58; and the weight of the second fetus was less than the first: 57. The ROC curve was plotted and the area under the curve (AUC) is 0.856 1, which were able to forecast the success rates well, the maximum value of the Youden index was 0.564 7 and the corresponding score was 168. Conclusions: maternal age, reasonability of weight gain during pregnancy, the complication of GDM, parity, and the weight of the second fetus less than the first are the influential prenatal factors on vaginal delivery of twin pregnancy. After assigning the influence weight of each influencing factor, when the total score reaches 168 the success rate of vaginal delivery is significantly improved.

[Expression and significance of Nek2B and ß-catenin in triple negative breast cancer].

Objective: To investigate the expression and significance of Nek2B and ß-catenin expression in triple negative breast cancer (TNBC) at molecule levels. Methods: By using the methods of bioinformatics [GEO2R online tool, gene ontology (GO) function analysis, KEGG biological pathway enrichment analysis], the differentially expressed genes were screened from TNBC microarray data.Expression levels of Nek2B and ß-catenin TNBC cell lines were detected by Western blot and qRT-PCR.From January 1, 2007 to December 31, 2012, eighty cases of TNBC were collected from the Second Hospital of Shanxi Medical University. The expression of Nek2B in TNBC tumor tissue was detected by immunohistochemistry and tissue microarray, and the relationship between Nek2B and clinical pathological characteristics of TNBC was analyzed. Results: Through bioinformatics analysis of the cDNA chip sets of 2 TNBC tumors(GSE38959,GSE27447), 998 differentially expressed genes were obtained in the initial screening, and 13 differentially expressed genes were revealed after intersection. The results of biological pathway analysis showed that the common differential expression genes were closely related to Wnt/ß-catenin pathway, among which Nek2 expression showed the greatest difference and was associated with poor prognosis. Expression intensity of Nek2B and repeated ß-catenin in the same TNBC cell line was consistent.The results of immunohistochemistry showed that the high expression of Nek2B was related to the high histological stage (G3;84.3% vs.37.9%, P<0.001), lymph node metastasis group (76.7% vs.54.1%, P=0.032), high Ki-67 positive index group (78.6% vs.52.6%, P=0.007) and ß-catenin positive expression group (72.5% vs.27.3%, P=0.018). Conclusions: The high level of Nek2B expression is related to a poor prognosis in TNBC patients. In TNBC tissues and cells, the expression of Nek2B is correlated with ß-catenin, suggesting that Nek2B may affect the occurrence and development of TNBC by regulating the Wnt/ß-catenin patients signaling pathway.

[Legionnaires' disease with pronounced cerebellar involvement: case report and literature review].

Objective: To summarize the clinical course, neuroimaging and cerebrospinal fluid (CSF) analyses of cerebellar dysfunction in Legionnaires' disease. Methods: A case of Legionnaires' disease with pronounced cerebellar involvement was reported. The related literatures published up to February 2019 were reviewed with "Legionella, legionellosis, legionnaires' disease, cerebellum, cerebellar" as the keywords in CNKI, Wanfang and PubMed databases. Results: A 69-year-old man complained of anorexia and diarrhea for several days. He was subsequently admitted to the hospital after he had fever, ataxia, dysarthria and involuntary tremor. Chest CT revealed right lower lobe pneumonia. Routine urinalysis showed hematuria and proteinuria. Serum alanine transaminase was 52 U/L, creatinine 137 µmol/L, sodium 128 mmol/L, and creatine kinase 6 893 U/L. Cranial CT was normal. Analysis of CSF showed mildly elevated total protein. Legionella colonies isolated from bronchoalveolar lavage fluid was positive by PCR. After initial treatment with moxifloxacin and azithromycin for 7 days, the fever and neurological symptoms persisted. Corticosteroid therapy was administered for 3 days, the fever resolved, whereas the neurological symptoms improved gradually and slowly by 4 weeks of antibiotic therapy. Finally, successive serological test confirmed Legionella pneumophila serogroups 6 and 7 by indirect immunofluorescence. Twenty-one literatures with 23 cases were reviewed, and plus our case, there were a total of 24 cases for analysis. There were 16 males and 8 females, aged from 22 to 71 years. Ataxia and dysarthria were the cerebellar symptoms most frequently reported, occurring in 22 and 18 cases, respectively. All patients had various central and peripheral neuropathies during their illness. Neuroimaging and analysis of CSF was reported in 21 cases. There were no abnormalities in 18 cases of cranial imaging, 1 case with slight hydrocephalus on cranial CT, and 3 cases with hyperintensity in the splenium of corpus callosum on cranial MRI. Eighteen cases of CSF analyses were normal, whereas 1 case with elevated lymphocytes and 3 cases with elevated proteins. Nine cases were eventually identified as Legionella pneumophila serotype 1 by urinary antigen detection, 1 case as Legionella pneumophila serogroups 6 and 7, while the remaining 14 were unknown serotype. Long-term neurologic follow-up showed that 3 cases recovered completely in the first week, while 19 cases improved slowly in the following 3 weeks, and 13 cases had persistent deficits of gait or speech after 3 months. Conclusions: Legionellosis with cerebellar insufficiency is rare. It may be misdiagnosed in the onset of illness. After treatment, there is a trend of slow recovery and neurological symptoms may persist in long-term follow-up.

[Influence of the blood gas composition and mechanical ventilation parameters of the medical evacuation prognosis of critically ill patients.]

The clinical estimation of the state of patient is one of the basic components of the checking of the state of patient, but more precise and more objective indices today become necessary. The arterial blood gases analysis helps to select the optimum regime of mechanical ventilation. The medical evacuation of the critically ill patients frequently requires the correction of the parameters of respiratory support. The conducted investigations showed that the prognostics of unfavorable outcome within the first three days from the moment of the medical evacuation are hypercapnia, which exists during the process of evacuation in spite of the correction of the parameters of mechanical ventilation, reduction in the saturation of the arterial blood. The forecast of the medical evacuation is located as well in the direct correlation with the manifestation of acidosis, and at the moment of the completion of the transfer of the patient the greatest prognostic significance they possess the low level of the partial tension of oxygen in the artery. The application of a portable express- analyzer of blood gases permits implementation of correction parameters of respiratory support and to increase quality and safety of the medical evacuation of patients.

[Applicational value of modified pancreaticojejunostomy and risk factors of pancreatic fistula following pancreaticoduodenectomy].

Objective: To compare the efficacy of modified pancreaticojejunostomy with traditional pancreaticojejunostomy following pancreaticoduodenectomy, and to investigate the risk factors of postoperative pancreatic fistula. Methods: Clinical data of 68 patients who underwent pancreaticoduodenectomy between October 2017 and October 2018 at the Second Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital was retrospectively collected and analyzed.According to the method of pancreaticojejunostomy, the patients were divided into two groups: modified pancreaticojejunostomy group (34 patients) and traditional pancreaticojejunostomy group (34 patients). There were 18 males and 16 females, aged (60.4±9.6) years of modified pancreaticojejunostomy groups; there were 17 males and 18 females, aged (58.9±10.9) years of traditional pancreaticojejunostomy group. The major postoperative complications such as pancreatic fistula were compared between the two groups, and the risk factors of postoperative pancreatic fistula were analyzed by univariate and multivariate analyses. Results: All of the 68 operations were successfully completed. The overall incidence of postoperative complications was 51.5% (35/68). The incidence of postoperative pancreatic fistula was 13.2% (9/68), of which all were cases of grade B.There were 16 patients (23.5%) occurred with abdominal infection, and 11 patients (16.2%) occurred with delayed gastric emptying, including 1 case of grade A, 1 case of grade B and 9 cases of grade C.And 9 patients (13.2%) occurred with postoperative bleeding was, including 2 cases of mild bleeding, 5 cases of moderate bleeding, and 2 cases of severe bleeding.Biliary leakage occurred in one patient (1.5%) and chylous leakage occurred in two patients (2.9%). The modified pancreaticojejunostomy could significantly reduce the incidence of postoperative bleeding compared with control group (χ(2)=4.610, P=0.032). And there were no significant differences for other postoperative complications between the two groups (all P>0.05). According to the results of univariate analysis: age, intraoperative bleeding and diameter of pancreatic tube were related factors affecting postoperative pancreatic fistula (P=0.025, 0.019, 0.017, respectively). The results of multivariate analysis showed that intraoperative bleeding>400 ml and diameter of pancreatic tube <3 mm were independent risk factors of pancreatic fistula following pancreaticoduodenectomy (P=0.025, 0.008, respectively). Conclusion: The modified pancreaticojejunostomy is feasible with advantages of reducing postoperative bleeding following pancreaticoduodenectomy.

[Discussion on pT3 staging in TNM staging of AJCC 8(th) edition gallbladder carcinoma].

Objective: To discuss the rationality of stage pT3 in the AJCC 8(th) TNM criteria of gallbladder carcinoma. Methods: A retrospective study was performed to analyze the clinical and pathological data of 88 patients with pT3 gallbladder carcinoma admitted to Department of Second Biliary Surgery of Eastern Hepatobiliary Surgery Hospital, affiliated to Naval Medical University from May 2013 to September 2018.pT3 stage tumors were divided into two groups: (1) pT3a stage: tumors had penetrated serosa but not directly invaded liver and/or an adjacent organ or structure; (2) pT3b stage: tumor penetrating serosa and directly invaded liver and/or an adjacent organ or structure. There were 45 patients with pT3a stage, including 15 males and 30 females, aged 36 to 80 years, with a median age of 59 years; 43 patients with pT3b, including 24 males and 19 females, aged 41 to 78 years old, median aged 63 years old.Patients with pT3a and pT3b were further divided into two groups respectively: radical resection group and extended radical resection group according to surgical radicalization. Independent sample t-test was used for comparison between two groups with normal distribution measurement data. Wilcoxon rank sum test was used between groups of non-normally distributed measurement data.The comparison of the count data was performed by χ(2) test or Fisher exact probability method. Survival analysis was performed using Kaplan-Meier method, and survival rate was compared using Log-rank test. Results: (1)Serum total bilirubin(15.6(90.3)mmol/L), albumin(40.2(4.8)mmol/L), and CA19-9(132.90(455.78)U/ml) levels in pT3b patients were higher than that in pT3a patients(10.2(6.8)mmol/L, 41.8(4.9)mmol/L, 14.35(36.27)U/ml), respectively(Z=-3.816, -1.966, -3.739, all P<0.05),postoperative complication rate in pT3b patients(24.4%) was higher than that in pT3a patients(8.9%)(P<0.05),postoperative hospital stay(12(7)days) and overall hospital stay((26±17)days) of pT3b patients were longer than that of pT3a patients((10±5) days and (19±7)days) (P<0.05). (2) The 1-, 3-, 5-year survival rates of pT3b and pT3a patients were 53%,22%,22% and 69%, 46%,38%,and the median survival time was 13 months and 26 months, respectively. The difference in survival rates between the two groups was statistically significant(χ(2)=5.117, P=0.024). (3)The 1-, 3-year survival rates of extended radical resection group(n=19) and radical resection group(n=24) in the pT3b stage were 73%, 36% and 28%, 7%, respectively.The survival time was 20 months and 9 months,respectively,and the difference in survival rates between the two groups was statistically significant(χ(2)=4.976, P=0.026). Conclusions: pT3 gallbladder carcinoma could be further subdivided into pT3a stage and pT3b stage based on the TNM criteria of AJCC 8(th) gallbladder carcinoma. Extended radical resection for pT3b gallbladder carcinoma should be further considered after comprehensive assessment of the patient's basic condition and surgical tolerance.

[Optimization of the preanalytical phase of laboratory diagnostics in intensive care and disaster medicine.]

The use of point-of-care diagnostics can prevent a number of complications and leading to improved health outcomes for patients in critical condition. Research have shown that elongation of the preanalytic stage leading of errors of studies and changes the results of a number of laboratory parameters. The article presents the key problems associated with the elongation of the preanalytic stage and possible solutions to address the shortcomings of existing diagnostics.

MiR-365a-3p suppresses proliferation and invasion of Hep-2 cells through targeting ten-eleven translocation 1 (TET1).

miRNAs are among the most important factors that regulate gene expression. According to bioinformatic analysis, miR-365a-3p was predicted to interact with the TET1 mRNA. We predicted that it might affect tumor biological processes through TET1. TET1 interference and miR-365a-3p inhibitor constructs were generated. qRT-PCR was used to verify the expression level of miR-365a-3p and TET1 in Hep-2 and BESB-2B cells. qRT-PCR and Western blot were used to confirm the TET1 expression level in Hep-2 and miR-365a-3p inhibitor cells. Cell proliferation, cell cycle progression and cell invasion were further studied to identify the relationship between TET1 and miR-365a-3p. Luciferase reporter gene assays were used to find the binding site of miR-365a-3p in the 3'-UTR (3'-untranslated region) of the TET1 mRNA. TET1 was weakly expressed in Hep-2 cells and highly expressed in BESB-2B cells, while miR-143-3p and miR-365a-3p were highly expressed in Hep-2 cells and lowly expressed in BESB-2B cells. Inhibiting miR-365a-3p could up-regulate the expression of TET1. The negative effects of miR-365a-3p on cell proliferation, cell cycle progression and cell invasion could be abolished by TET1 interference. The binding site of miR-365a-3p was in the 3'-UTR of the TET1 mRNA. TET1 is one of the targets of miR-365a-3p. miR-365a-3p regulates the biological behavior of laryngeal cancer by down-regulating TET1.

[Clinical analysis of candidemia in immunocompetent patients].

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.