[Clinicopathological characteristics and immune microenvironment of breast squamous cell carcinoma].

Objective: To investigate the clinicopathological characteristics of breast squamous cell carcinoma and to analyze the relationship between its immune microenvironment tumor infiltrating lymphocytes (TILs) and prognosis. Methods: Forty-four cases of primary squamous cell carcinoma of the breast diagnosed and treated in the First Affiliated Hospital of Air Force Medical University, Xi'an, China from January 2006 to July 2022 were selected. Their clinicopathological characteristics were analyzed. The cell composition of TILs was evaluated using immunohistochemistry (Mainly markers of B lymphocytes, T lymphocytes and plasma cells). The relationship between TILs and prognosis was also analyzed. Results: The 44 patients of breast squamous cell carcinoma were all female and all were invasive carcinoma. Eight cases (8/44, 18.2%) were squamous cell carcinoma, while 36 cases (36/44, 81.8%) were mixed squamous cell carcinoma. The mixed components included non-specific carcinoma and spindle cell metaplastic carcinoma (17 cases each). One case contained ductal carcinoma in situ of the breast and 1 case contained tubular carcinoma. The proportion of squamous cell carcinoma was 10% to 90%. The cases with pure squamous cell carcinoma often had a large cystic cavity, which was lined by atypical squamous epithelium, while infiltrating squamous cell carcinoma nests were seen in the breast tissue around the cystic cavity. Immunohistochemical staining showed that p63 and CK5/6 were expressed in the squamous cell carcinoma component, but ER, PR and HER2 were not, except for one case of HER2 1+. The positive rates of TRPS1 and PDL-1 were 76% and less than 1%, respectively. Fifteen cases were in the high TILs group (TILs≥30%) and 29 cases were in the low TILs group (TILs<30%). Twenty-three patients were followed up for 5 to 118 months. Among them, 12 died within 3 years and 9 were alive at the end of the follow up. There was no significant difference in TNM stage, TILs and prognosis between simple squamous cell carcinoma and mixed squamous cell carcinoma. Conclusions: Breast squamous cell carcinoma can be divided into simple squamous cell carcinoma and mixed squamous cell carcinoma. There are differences in gross findings and histology between the simple and mixed squamous cell carcinoma of the breast. Sufficient samples should be taken to avoid missing the diagnosis of a minor squamous component. The prognosis of patients with high TILs is significantly better than that of patients with low TILs. The expression rate of TRPS1 in primary squamous cell carcinoma of breast is high and helpful to the differential diagnosis from metastatic squamous cell carcinoma.

[Functional analysis of virus-specific CD4(+)T cells and CD8(+)T cells in patients with liver injury caused by Epstein-Barr virus infection].

Objective: To analyze the functional differences between virus-specific CD4(+)T cells and CD8(+)T cells in patients infected with Epstein-Barr virus (EBV) who develop liver injury and those who do not. Methods: 45 cases of EBV infections were enrolled, including 28 cases developing liver injuries and 17 that did not. Mononuclear cells from peripheral blood were isolated. CD4(+)T cells and CD8(+)T cells were purified and cultured using recombinant EBV core antigen 2 (EBNA2) for 96 h with stimulation. The CCK-8 method was used to detect cell proliferation. Flow cytometry was used to detect the proportion of CD4(+)T cells and CD8(+)T cells. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of CD4(+)T cells secreting cytokines and CD8(+)T cells secreting molecular toxicity. Real-time quantitative PCR was used to detect the mRNA levels of transcription factors and molecular toxicity in CD4(+)T cell subsets. Flow cytometry was used to detect the immune checkpoints at molecular levels in CD8(+)T cells. The inter-group comparison was performed using a t-test or Mann-Whitney test. Results: There was no statistically significant difference (P > 0.05) in the proliferation proportion of peripheral blood mononuclear cells, CD4(+)T cells, and CD8(+)T cells after stimulation with recombinant EBNA2 between the EBV-infected non-liver injury group and the infected liver injury group (P > 0.05). There was no statistically significant difference in the proportion of CD4(+)T cells secreting related cytokines and the mRNA levels of transcription factors after stimulation with recombinant EBNA2 between the EBV-infected non-liver injury group and the infected liver injury group (P > 0.05).The levels of perforin secreted by CD8(+)T cells and granzyme B after stimulation with recombinant EBNA2 were higher in the EBV infection-induced liver injury group than those in the non-liver injury group [(75.51±23.33) pg/ml vs. (58.99±18.39) pg/ml, P = 0.017] [(117.8±44.55) pg/ml vs. (90.22±34.21) pg/ml, P = 0.034]. The mRNA levels of Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand in CD8(+)T cells in the liver injury group caused by EBV infection were approximately 1.5 and 1.2 times higher than those in the non-liver injury group, respectively, and the difference was statistically significant (P < 0.001), but there was no statistically significant difference in the proportional expression of programmed cell death-1 and cytotoxic T lymphocyte-associated antigen-4 in CD8(+)T cells between the EBV-infected non-liver injury group and infected liver injury group (P > 0.05) Conclusion: Patients with liver injury caused by EBV infection have strong virus-specific CD8(+) T cell toxic effects, which may mediate EBV-induced liver injury.

[A case of hypereosinophilia with diffuse pulmonary nodules].

We reported a case of a 36-year-old woman who presented with cough, dyspnea, hypereosinophilia, multiple pulmonary nodules and mediastinal lymphadenopathy. The percentage of eosinophils in bronchoalveolar lavage fluid (BALF) was as high as 65%. Pathogenic tests and cytologic examination of BALF were negative. Transbronchial lung biopsy and endobronchial ultrasound-guided transbronchial needle aspiration revealed only eosinophil infiltration. As the patient responded poorly to high-dose corticosteroids, a surgical lung biopsy was performed. The pathological diagnosis was angioimmunoblastic T-cell lymphoma. The patient received chemotherapy and achieved a partial response. Her eosinophil count returned to the normal range, and the pulmonary nodules on chest CT partially resolved.

[Clinicopathological and molecular genetic characteristics of ELOC mutated renal cell carcinoma].

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34ßE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34ßE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.

[Classification, diagnosis and treatment status of pulmonary hypertension from 2012 to 2019: a single center study in Yunnan province].

Objective: To analyze the classification, diagnosis and treatment status of patients with pulmonary hypertension (PH) in Yunnan province. Methods: This was a retrospective study. Hospitalized patients with PH at Yan'an Affiliated Hospital of Kunming Medical University from January 2012 to December 2019 were enrolled. The clinical data of enrolled patients, including demographic data, comorbidities, targeted drug therapy, echocardiography and right heart catheterization results, were obtained through the electronic medical record system. The composition ratio of PH, diagnosis and treatment were analyzed. Results: A total of 13 590 patients with PH were enrolled, accounting for 3.09% (13 590/440 056) of the total number of hospitalizations during the same period. The composition of PH was predominantly pulmonary arterial hypertension (PAH) (55.50% (7 542/13 590)), followed by pulmonary hypertension (PH) caused by left heart disease (24.16% (3 284/13 590)). Among them, PAH could be subdivided into four types: idiopathic pulmonary arterial hypertension (IPAH), PAH associated with connective tissue disease, PAH associated with portal hypertension, and PAH associated with congenital heart disease (CHD-PAH), with CHD-PAH as the predominating type (98.09% (7 398/7 542). Patients with PAH were predominantly adolescents. In hospitalized patients with PH, from 2012 to 2019, the proportion of children and adolescents showed a decreasing trend from year to year, and the proportion of middle-aged and older adults showed a significant increasing trend, and the proportion of female patients showed a gradual decreasing trend, and the proportion of patients with comorbid hypertension, diabetes mellitus, coronary artery disease, arrhythmia, and pneumonia showed an increasing trend. A total of 1 034 patients (7.61% (1 034/13 590)) underwent right heart catheterization. The concordance rate between echocardiographic and right heart catheterization findings was (86.98% (875/1 006)). A total of 2 574 (18.94%) of PH patients were treated with PAH targeted drugs, of which 58.16% (1 497/2 574) were treated with monotherapy. Among the PH patients treated with PAH targeted drugs, the majority of patients were PAH patients (86.44% (2 225/2 574)), and 83.53% (2 150/2 574) patients treated with PAH targeted drugs were CHD-PAH. Conclusions: Hospitalized PH patients in our center between 2012 and 2019 are predominantly CHD-PAH, and the proportion of patients receiving right heart catheterization and targeted drug therapy is relatively low. The percentage of middle-aged and elderly PH patients shows an increasing trend from year to year, as well as the percentage of those with concomitant comorbidities.

[The impact of the dosage of intraoperative opioids on postoperative survival outcomes in patients with pancreatic cancer].

Objective: To investigate the impact of the dosage of intraoperative opioids on postoperative survival of pancreatic cancer patients who underwent pancreatectomy. Methods: The clinical data of 95 patients with pancreatic cancer who underwent pancreatectomy at Harbin Medical University Cancer Hospital from September 2013 to August 2018 were retrospectively collected. Dosage of intraoperative opioid medications was converted to fentanyl equivalent dose. Patients were divided into high-dose group (fentanyl consumption ≥2.21 mg, n=46) and low-dose group (fentanyl consumption<2.21 mg, n=49) according to the median intra-operative fentanyl equivalents. The relapse-free survival (RFS) and overall survival (OS) between the two groups were compared. Cox proportional hazards regression model was used to analyze the impact of important covariates on RFS and OS. Results: RFS of patients in low-dose group at 1, 3 and 5 years was 75.5%, 26.5% and 15.2% respectively. OS of patients in low-dose group at 1, 3 and 5 years was 77.6%, 32.5% and 24.4% respectively. RFS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 23.9% and 12.0% respectively. OS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 37.0% and 15.0%. There was no significant difference in RFS and OS between the two groups (all P>0.05). Multivariate Cox analysis showed that dosage of intraoperative fentanyl was not associated with RFS (HR=1.205, 95%CI: 0.737-1.970, P=0.456) or OS (HR=1.062, 95%CI: 0.634-1.778, P=0.818). Conclusion: Dosage of intraoperative opioid has no effect on RFS and OS in pancreatic cancer patients undergoing pancreatectomy.

[Effects of primary preventive treatment under endoscope for esophageal and gastric varices on bleeding rate and its relevant factors].

Objective: To investigate the effects of primary preventive treatment under endoscope for esophageal and gastric varices on bleeding rate and its relevant factors. Methods: 127 cases with liver cirrhosis accompanied with esophageal and gastric varices without bleeding history were included in the endoscopic and non-endoscopic treatment group, respectively. Informed consent was obtained from both groups. Gastric varices (Lgf) and esophageal varices (Leg) were diagnosed according to LDRf classification criteria, and the corresponding treatment scheme was selected according to the recommended principle of this method.The incidence rate of bleeding from ruptured esophageal varices were observed at 3, 6 months, and 1, and 2 years in the treated and the untreated group, and the patients with different Child-Pugh scores were followed-up for 2 years. Gender, age, etiology, varicose degree, Child-Pugh grade, platelet count, prothrombin activity, portal vein thrombosis, collateral circulation, portal vein width and other factors affecting the bleeding rate were assessed. Measurement data were described as mean ± standard deviation (x¯±s), and qualitative data of categorical variables were expressed as percentage (%), and χ2 test was used. Results: 127 cases were followed up for 2 years. There were 55 cases in the endoscopic treatment group (18 cases underwent band ligation, 2 cases underwent band ligation combined with tissue adhesive embolization, 28 cases underwent sclerotherapy, and 7 cases underwent sclerotherapy combined with tissue adhesive embolization). Recurrent bleeding and hemorrhage was occurred in 5 (9.1%) and 28 cases (38.9%), respectively (P<0.05). In addition, there were 72 cases in the untreated group (P<0.05). Severe varicose veins proportions in treated and untreated group were 91.1% and 85.1%, respectively (P>0.05). There was no statistically significant difference in liver cirrhosis-related medication and ß-blocker therapy between the treated and untreated group (P>0.05). There was no statistically significant difference in the bleeding rate between the different treated groups (P>0.05). The bleeding rates at 3, 6 months, 1, and 2 years in endoscopic treated and untreated group were 2.00% vs. 2.59% (P>0.05), 2.30% vs. 5.88% (P>0.05), 3.10% vs. 7.55% (P>0.05) and 4.00% vs. 21.62% (P<0.05), respectively. All patients with Child-Pugh grade A, B and C in the treated and the untreated group were followed-up for 2 years, and the bleeding rates were 1.8% vs. 8.1% (P<0.05), 1.1% vs. 9.4% (P<0.05) and 9.1% vs. 10.1% (P>0.05), respectively. There were statistically significant differences in the rupture and bleeding of esophageal and gastric varices, varices degree, Child-Pugh grade and presence or absence of thrombosis formation in portal vein (P<0.05); however, no statistically significant differences in gender, age, etiology, platelet count, prothrombin activity, collateral circulation and portal vein width (P>0.05). There was no intraoperative bleeding and postoperative related serious complications in the treated group. Conclusion: The risk of initial episodes of bleeding from esophageal and gastric varices is significantly correlated with the varices degree, Child-Pugh grade, and portal vein thrombosis. Primary preventive treatment under endoscope is safe and effective for reducing the long-term variceal bleeding risk from esophageal and gastric varices.

[Diagnostic value of surgical lung biopsies for diffuse parenchymal lung disease: the change of disease spectrum in the past 28 years in a single institution in China].

Objective: To investigate the changes of disease spectrum in diffuse parenchymal lung disease (DPLD) diagnosed by surgical lung biopsy, and to explore the diagnostic value of surgical lung biopsy in DPLD. Methods: Four hundred and fifty-five consecutive DPLD patients, who underwent surgical lung biopsy in Peking Union Medical College Hospital during the past 28 years, were analyzed retrospectively. Results: There were 211 males and 244 females. The average age at biopsy was (45±14) years. Four hundred and eleven cases (90.3%) were diagnosed by pathologic findings. Four hundred and forty-one cases (96.9%) were diagnosed by clinical-radiologic-pathologic multidisciplinary discussion. The 30-day mortality and 90-day mortality were 2.4% and 3.3% respectively. The disease spectrum included interstitial pneumonia in 209 cases (45.9%) (nonspecific interstitial pneumonia in 105 cases, usual interstitial pneumonia in 33 cases), other miscellaneous DPLD in 166 cases (36.5%) (including hypersensitivity pneumonitis in 49 cases), tumor in 39 cases (8.6%), and infectious diseases in 27 cases (5.9%). In the three consecutive periods (1993-2002, 2003-2012 and 2013-2020), the number of biopsies was 76 (16.7%), 297 (65.3%) and 82 (18%) respectively. The disease spectrum changes over time: in the above three periods, the percentage of interstitial pneumonia in DPLD was 68.4%, 45.1% and 28%, other miscellaneous DPLDs were 22.4%, 39.4% and 39.0%, the tumors were 2.6%, 7.4% and 18.3%, the infectious diseases were 5.3%, 5.1% and 9.8%. Conclusions: This study presented the changes of disease spectrum in DPLD diagnosed by surgical lung biopsy through single center real-world data, reflecting the progress of clinicians' understanding of DPLD and interstitial pneumonia. Surgical lung biopsy is still valuable for some difficult and complicated DPLD cases.

[Expert consensus on measurement and clinical application of serum HBV RNA in patients with chronic HBV infection].

Since the discovery of circulating hepatitis B virus (HBV) RNA in the peripheral blood of patients with chronic hepatitis B in 1996, a growing number of studies have focused on clarifying the biological characteristics and clinical application value of serum HBV RNA. This consensus mainly summarizes the research progress of serum HBV RNA existing profiles, quantitative detection methods, and current clinical applications. In order to better apply this indicator for the clinical management of patients with chronic HBV infection, recommendations on quantitative detection target regions, detection results, and clinical applications are put forward.

[Clinical characteristics of patients with acute pulmonary embolism in high altitude area of Yunnan province in China].

Objective: To analyze the clinical features of patients with acute pulmonary embolism (APE) living in high altitude area of Yunnan province. Methods: This was a cross-sectional retrospective study. APE patients, hospitalized in our hospital between January 2017 and December 2019, were included. The selected patients were divided into low-risk group, medium-risk group and high-risk group according to risk stratification. The clinical data of patients, including demographic data, the main symptoms, risk factors of APE, heart rate and systolic blood pressure and laboratory testing results (D-dimer, cardiac troponin I (cTNI), N terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography and electrocardiogram examination results, were obtained through the electronic medical record system. The clinical characteristics of selected patients were analyzed. Results: A total of 392 patients, aged (63.5±15.7) years, 224 males (57.14%), were included in this study and there were 59 low-risk, 304 medium-risk and 29 high-risk patients in this cohort. The main clinical manifestations were chest pain (157(40.05%)), dyspnea (107(27.30%)), hemoptysis (55(14.03%)), syncope as the first symptom (20(5.10%)), and only 6 cases (1.53%) presented with the typical "Virchow's triad". Most of the patients were accompanied by atypical chest tightness (223(56.89%)) and cough (208(53.06%)). The main risk factors were venous thrombosis of lower limbs (179(45.66%)), hypertension (138(35.20%)), surgery (63(16.07%)), and chronic obstructive pulmonary disease (COPD) (62(15.82%)). There were 57 cases (14.54%) of coronary heart disease, 57 cases (14.54%) of diabetes, 51 cases (13.01%) of cerebral infarction, 47 cases (12.00%) of advanced age, 15 cases (3.83%) of tumor, 7 cases (1.79%) of activity restriction, 6 cases (1.53%) of pregnancy and 4 cases (1.02%) of hormone use in this cohort. The proportion of lower extremity venous thrombosis was significantly higher in low-risk group than in medium-risk group (P<0.01), COPD was more common in high-risk and medium-risk groups than in low-risk group (P<0.01), hypertension was more common in high-risk group than in medium-and low-risk groups (P<0.01). The proportion of advanced age was significantly higher in medium-risk group than in low-risk group (P<0.01). There were no significant differences in RBC and hemoglobin level between low-, medium-and high-risk groups (P>0.05). The level of D-dimer was significantly higher in high-risk group than in medium-and low-risk groups (P<0.05). Levels of NT-proBNP and cTNI were significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). Increased proportion of cTNI and NT-proBNP was significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). There were 105 (26.79%) patients with pulmonary hypertension (PAH). The incidence of PAH was significantly higher in high-risk group than in low-risk group (P<0.01). There were 104 patients (26.53%) with right ventricular enlargement, and the incidence of right ventricular enlargement was significantly higher in high-risk group than in medium-and low-risk groups (P<0.01). Characteristic changes of electrocardiogram in patient with APE were T-wave inversion of limb leads (98(25.00%)), followed by SⅠQⅢTⅢ (83(21.17%)). Conclusions: The main clinical manifestations of APE in Yunnan high altitude area are chest pain and dyspnea, and syncope is the first symptom in some patients, but the typical "Virchow's triad" is rare. The most common risk factors are lower extremity venous thrombosis, hypertension, and COPD. Clinical symptoms, risk factors and laboratory examination results differ among patients with different risk stratification.

[Preliminary study on smoking-related behaviors of people aged 60 and over suffering from respiratory diseases in Shangqiu area].

The purpose of this study is to explore the smoking-related behaviors of people ≥60 years of age with respiratory diseases in Shangqiu area. A total of 550 patients with respiratory diseases ≥60 years old who were treated at the First People's Hospital of Shangqiu from April 2015 to April 2017 were selected as the survey subjects through random sampling. Among them, there were 351 males and 199 females; the age ranged from 60 to 86 (72.85±5.71) years old. Follow-up until April 2020, and the follow-up was 3 years or more and related information and death information were also collected. The multivariate Cox proportional hazard regression model was used to analyze the influence of smoking behavior in the survey subjects on the death risk of people with respiratory diseases ≥ 60 years old. A total of 550 cases were included in the survey, and 25 cases were lost to follow-up. The effective number was 525, and the survey effective rate was 95.45%. Among the 525 patients, 336 (64.00%) were males and 189 (36.00%) were females. The age ranged from 60 to 86 (72.69±5.64) years old. The education level was mainly high school and technical secondary school, accounting for 39.24% of the total population. The primary diseases included tracheitis/bronchitis, asthma, pneumonia, COPD and lung cancer. Among 525 patients with respiratory diseases ≥60 years old, non-smokers accounted for 11.05% (58/525), smokers accounted for 68.00% (357/525), and quitters accounted for 20.95% (110/525). The duration of smoking was more than 20 years, accounting for 33.33% (175/525). The smoking intensity was mainly moderate, accounting for 33.90% (178/525). The duration of smoking cessation was mainly<5 years, accounting for 8.76% (46/525). Follow-up until April 2020, the mortality rate of 525 patients with respiratory diseases ≥60 years old was 14.10% (74/525). Cox regression analysis showed that smoking duration, smoking intensity, cumulative smoking amount, and duration of smoking cessation were the influencing factors of death in patients with respiratory diseases ≥60 years old in Shangqiu area (P<0.05). It can be seen that smoking duration, smoking intensity, cumulative smoking amount, and smoking cessation duration may be independent risk factors for death in patients with respiratory diseases ≥ 60 years old in Shangqiu area, and may increase the relative risk of death.

Impact of implementation of a breech clinic in a tertiary hospital.

BACKGROUND: The incidence of breech presentation in single pregnancies at term is between three to 5 %. In order to support eligible women in their choice of mode of delivery, a dedicated breech clinic with a care pathway was developed in December 2015 in a tertiary referral centre in Brussels. The primary objective of this study was to evaluate the vaginal birth rate before and after the introduction of a dedicated breech clinic. The secondary objective was to compare the early neonatal outcomes before and after the breech clinic was introduced. METHODS: This was a single centre retrospective and prospective study. The inclusion criteria were term (from 37 weeks), singleton fetus and breech presentation at delivery. The exclusion criteria were suspected intrauterine growth restriction, severe fetal malformations and intrauterine fetal demise. We used a composite outcome as an indicator of neonatal morbidity and mortality. RESULTS: After the introduction of the breech clinic, we observed a significant increase in planned vaginal delivery from 7.4% (12/162) to 53.0% (61/115) (OR: 13.5; 95% CI: 6.7-27.0). The effective vaginal breech delivery rate (planned and unexpected) significantly increased from 4.3% (7/162) pre-implementation of breech clinic to 43.5% (50/115) post-implementation (OR: 17.0; 95% CI: 7.3-39.6). Neonatal outcomes were not statistically different between the before and after periods. CONCLUSION: The introduction of a dedicated breech clinic has led to an increase in vaginal deliveries for breech babies without adversely affecting neonatal outcomes.

Anaphylaxis in pregnancy: a population-based multinational European study.

Anaphylaxis in pregnancy is a rare but severe complication for both mother and infant. Population-based data on anaphylaxis in pregnancy are lacking from mainland European countries. This multinational study presents the incidence, causative agents, management and maternal and infant outcomes of anaphylaxis in pregnancy. This descriptive multinational study used a combination of retrospective (Finnish medical registries) and prospective population-based studies (UK, France, Belgium and the Netherlands) to identify cases of anaphylaxis. Sixty-five cases were identified among 4,446,120 maternities (1.5 per 100,000 maternities; 95%CI 1.1-1.9). The incidence did not vary between countries. Approximately three-quarters of reactions occurred at the time of delivery. The most common causes were antibiotics in 27 women (43%), and anaesthetic agents in 11 women (17%; including neuromuscular blocking drugs, 7), which varied between countries. Anaphylaxis had very poor outcomes for one in seven mothers and one in seven babies; the maternal case fatality rate was 3.2% (95%CI 0.4-11.0) and the neonatal encephalopathy rate was 14.3% (95%CI 4.8-30.3). Across Europe, anaphylaxis related to pregnancy is rare despite having a multitude of causative agents and different antibiotic prophylaxis protocols.

[Clinical characteristics of patients with Klebsiella pneumoniae pyogenic liver abscess].

Objective: To summarize the clinical features of patients with Klebsiella pneumoniae pyogenic liver abscess(KP-PLA). Methods: Clinical data of 133 patients with pyogenic liver abscess(PLA) and positive results of blood or pus culture were retrospectively analyzed in Huashan Hospital Affiliated to Fudan University from 2009 to 2018. According to the culture results, patients were divided into KP-PLA group (n=92) and non-KP-PLA group (n=41). Results: KP-PLA and non-KP-PLA were similar in gender composition with males accounting for 67.39% and 70.73%, and had age of (56.8±13.8) years and (55.0±13.0) years (χ(2)=0.146, 0.708, P>0.05) respectively. The underlying diseases were more common in KP-PLA group, including diabetes accounting for 45.65% and 24.39%, and hypertension accounting for 32.61% and 14.63% (χ(2)=5.384, 4.642, P<0.05) respectively. Patients with KP-PLA had more invasive infections beyond liver than those with non-KP-PLA, which were 27.17% and 9.76% (χ(2)=5.046, P=0.025). The laboratory results showed that hemoglobin levels in KP-PLA and non-KP-PLA were (109.88±20.97) g/L and (97.75±20.25) g/L (t=3.086, P=0.002). Serum alkaline phosphatase levels were 146.50 (114.50, 237.50) U/L and 220.50 (120.00, 316.75) U/L in KP-PLA and non-KP-PLA (U=2 239.500, P=0.048) patients. Conclusions: KP-PLA mainly develops in middle-aged and elderly men, especially those with diabetes and hypertension. Patients with KP-PLA need to be paid more attention for invasive manifestations beyond liver.

[Clinical features of anti-myelin oligodendrocyte glycoprotein antibody-associated diseases in children with cortical encephalitis].

Objective: To describe the clinical features of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive cortical encephalitis in children. Methods: Patients who were hospitalized in Beijing Children's Hospital from June 2018 to October 2019, with positive MOG antibodies and phenotype of cortical encephalitis were retrospectively analyzed. Cell-based assays (CBAs) were used to test MOG antibodies. Results: Five patients had the phenotype of cortical encephalitis during follow-up, with 3 females and 2 males. The age of onset ranged from 8 years to 12 years and 1 month. At the last follow-up, 3 cases exhibited a monophasic course and 2 cases were with relapse and remission courses. Six out of 8 episodes which had the phenotype of cortical encephalitis presented with seizures, among which 3 episodes had status epilepticus. None had recurrent seizures during remission. Other symptoms included fever (7/8), headache and vomiting (4/8), somnolence (3/8) and hemiplegia (1/8). Unilateral cortical swelling was observed in cerebral magnetic resonance imaging (MRI) of all patients, without any hemorrhage and necrosis. White blood cell (WBC) counts of cerebrospinal fluid increased, ranging from8×10(6)/L to 186×10(6)/L. All patients recovered well after treatment with intravenous immunogloblin and glucocorticoid. Two patients had relapses during follow-up and were additionally treated with mycophenolate mofetil. Conclusions: Anti-MOG antibodies can induce cortical encephalitis. In clinical setting, fever, headache and seizures are common, however, severe consciousness disturbance and local neurological deficits are rare in these patients. Cerebral MRI shows unilateral cortical swelling without any hemorrhage and necrosis. Usually, immunotherapy works well. No patients exist repeated seizures in remission, but some patients may have relapses.

[Preliminary study of the clinical value of colposcopy in diagnosing vagina invasion in cervical cancer].

Objective: To explore the preliminary clinical values of colposcopy in the diagnosis of vaginal invasion in cervical cancer. Methods: A retrospective review of the clinical records of patients (31 cases) with cervical cancer treated in Xuzhou Cancer Hospital from April 2015 to August 2019. For those with early-stage cervical cancer and the vagina invasion being difficult to be determined, those with advanced cervical cancer and the scope of vaginal invasion being difficult to be judged, and those with obvious vaginal tumor and underexposed cervix or inconspicuous cervical lesion and the primary location needing to be identified, colposcopy-guided vaginal and cervix biopsy were performed before treatment. Results: (1) Image characteristics of colposcopy and pathological diagnosis: among 31 cases, 30 of them had the similar images of vagina and cervix. The images were dense acetowhite and (or) thick mosaic, coarse punctate and atypical vessels. Lugol's staining was uniformly bright yellow or brown. Pathological biopsy of vaginal wall: 27 cases were metastatic carcinoma, 3 cases were vaginal intraepithelial neoplasia (VaIN) Ⅱ-Ⅲ. One case showed dense acetowhite epithelium and atypical vessels image in cervix and thin acetowhite epithelium in upper 1/3 vagina which disappeared in two minutes; the results of vaginal biopsy was chronic inflammation. (2) Vaginal invasion diagnosed by colposcopy: among 31 cases, 14 of them without invasion of uterine side, vaginal invasion was judged as followed by colposcopy, being consistent with biopsy: 1 case of chronic vaginitis, 2 cases VaINⅡ, 1 case VaINⅢ, 6 cases upper 1/3 vagina invasion, 4 cases lower 1/3 vagina invasion. Among 10 cases with invasion of uterine side, vaginal invasion were identified by colposcopy, being consistent with biopsy: 4 cases upper 1/3 vagina invasion and 6 cases upper 1/2 vagina invasion. Five cases who had clinical diagnosis of vaginal cancer were diagnosed as cervical cancer with vaginal invasion by colposcopy, being consistent with biopsy. Two cases with no obvious lesions of cervix and vagina were diagnosed as cervical cancer with vaginal invasion by colposcopy, being consistent with cervical and vaginal biopsy: 1 case with stage Ⅳ (transfer to the left supraclavicular lymph node) and 1 case with stage Ⅱ a1. Conclusions: Colposcopy and multi-point biopsy have complementary diagnostic value for the cervical cancer cases that the invasion and scope of vagina are difficult to be determined by physical examination and (or) imaging examination. Thus the range of vaginal resection for patients underwent operation and the lower boundary of pelvic radiation field for those underwent radiotherapy could be fixed, so as to make the treatment much more individualized and humanized; the indications need further discussion.

[Application of the new serum markers in the research and development of innovative hepatitis B drugs].

Chronic hepatitis B (CHB) poses a serious threat to the health of the Chinese people. Viral markers are of great significance during antiviral therapy and research and development of innovative drugs. However, traditional serovirological markers such as HBV DNA and hepatitis B surface antigen (HBsAg) have certain limitations in assessing the efficacy of antiviral treatment and accurately reflecting the transcriptional activity of covalently closed circular DNA (cccDNA). In recent years, the role of new viral markers such as HBV RNA, hepatitis B core-related antigen (HBcrAg) and quantitative anti-hepatitis B core protein (qAnti-HBc) have attracted more and more attention because of accurately reflecting the transcription activity of cccDNA, determining the therapeutic effect and predicting the risk of recurrence after drug discontinuation. This article briefly introduces the application of new and old markers in various stages of antiviral therapy in CHB patients, and combines the application of new viral markers in the evaluation of drug efficacy, and expounds its possible role in the research and development of new antiviral therapy.

[Hereditary protein S deficiency: survey results from a Chinese pedigree].

Objective: To investigate the clinical characteristics and gene mutation, and analyze the association between genotype and phenotype of hereditary protein S deficiency in a Chinese pedigree. Methods: Hereditary protein S deficiency was diagnosed in January 2016 in our hospital. A total of 26 family members were surveyed in this study. Blood samples and clinical data were collected from them, and mutations were identified by Sanger sequencing. Pathogenicity of gene mutations was predicted by protein function prediction software including SIFT, PolyPhen_2, nsSNPAnalyzer and MutPred2. Swiss Model (https://swissmodel.expasy.org/) was used to perform homology modeling of the tertiary structure of the protein S wild-type and mutant-type, and observe the impact of gene mutation on the tertiary structure of the protein. Results: Four out of 26 family members of 4 generations were clinically diagnosed with hereditary protein S deficiency. The proband presented with recurrent pulmonary embolism and venous thromboembolism of the lower extremities, and her uncle and mother had a history of venous thromboembolism. Sequencing revealed a mutation in the c.200A>C gene in the second exon of the PROS1 gene of proband and part of her families (Ⅱ2, Ⅱ6, Ⅲ4, Ⅳ2). The prediction results of this gene mutation performed by SIFT, PolyPhen_2, nsSNPAnalyzer, MutPred2 were all harmful. The results of Swiss-Model homology modeling showed that the 67th amino acid was mutated from glutamic acid to alanine because of this gene mutation. Conclusion: A gene mutation cDNA (c. 200A>T) is identified in a Chinese pedigree with hereditary protein S deficiency. This gene mutation may reduce protein S activity, which may cause recurrent pulmonary embolism and venous thromboembolism of the patients.

[A randomized controlled study of peramivir, oseltamivir and placebo in patients with mild influenza].

Objectives: To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza. Methods: This was a randomized, double-blind, double-dummy, placebo and positive control, multicenter clinical trial, comparing peramivir trihydrate with oseltamivir and placebo. The inclusive criteria were 15-70 years old, onset within 48 h, positive rapid influenza antigen test, and febrile (>38℃) accompanied with at least two associated symptoms. The severe cases complicated with chronic pulmonary and cardiac diseases, malignancies, organ transplantation, hemodialysis, uncontrolled diabetes, immunocompromised status, pregnancy and coexistence of bacterium infections were excluded. All patients were randomized 2∶2∶1 to receive peramivir, oseltamivir and placebo respectively. The primary endpoint was the disease duration, the secondary endpoints included time to normal axillary temperature and normal living activities, viral response, and adverse effects. Results: Following informed consent, 133 patients were included in this study. Four patients were exclude due to missing medical records, not fitting inclusion or exclusion criteria and poor compliance. A total of 129 patients were finally analyzed, including 49 cases, 54 cases and 26 cases in peramivir group, oseltamivir group and placebo group. The median disease duration were 96 (76, 120) hours, 105 (90,124) hours, and 124 (104, 172) hours in three groups respectively (P>0.05) . The time to normal axillary temperature, normal living activities and viral response were not significantly different in three groups (P>0.05) . Conclusion: The value of antiviral therapy in patients with mild influenza needs to be further determined.

[Short-term effects of air pollution on lung function of school-age children in Hangzhou].

A total of 1 685 school-age children selected from Hangzhou received lung function testing to evaluate the short-term effects of air pollution on their lung function. The results showed that in every 10 µg/m(3) increase of average concentration of PM(2.5) and PM(10) on the day of the test and the day before the test,peak expiratory flow (PEF) decreased 0.039 (95%CI: 0.012-0.067) L/s and 0.031 (95% CI:0.011-0.051) L/s,respectively. When the average concentration of SO(2) increased 10 µg/m(3) on the day of test and the day prior to the test, PEF and 75% of the forced vital capacity that has not been exhaled (MEF(75)) decreased 0.437 (95%CI: 0.217-0.658) L/s and 0.396 (95%CI: 0.180-0.613) L/s. After being adjusted for NO(2),with every 10 µg/m(3) increase of average concentration of PM(2.5) and PM(10) on the day of the test and the day before the test,PEF and MEF(75) decreased 0.056 (95%CI: 0.028-0.085), 0.053(95%CI: 0.027-0.081) and 0.047 (95%CI: 0.026-0.068) L/s,0.044 (95%CI: 0.023-0.065) L/s on the day before the test, respectively. The results indicate that air pollution have short-term and lag effects on lung function of school-age children in Hangzhou.