Role of oedema and shrinkage patterns for prediction of response to neoadjuvant chemotherapy and survival outcomes in luminal breast cancer.

AIMS: To explore the independent and additional value of oedema and shrinkage patterns for predicting the disease-free survival (DFS) and neoadjuvant chemotherapy (NAC) response in luminal breast cancer (BC). MATERIALS AND METHODS: Patients with luminal BC who underwent NAC were enrolled in this study from 2017 to 2022. Traditional MRI features include BI-RADS-based MRI descriptors, tumor size, and ADC values, while emerging MRI features include oedema and shrinkage patterns, all of which were evaluated before, early, and after NAC. The changes in features during NAC were also evaluated. The value of features was evaluated through univariate, multivariate analyses. RESULTS: A total of 258 patients were enrolled in this study, of which 77 responded to NAC. Diffuse oedema, stable or increased oedema during early NAC were adverse predictors for treatment response, while a greater reduction in tumor size and increase in ADC value were favorable predictors (all P<0.05). Furthermore, 20 of 60 patients who were followed up experienced recurrence. Diffuse oedema, pre-pectoral or subcutaneous oedema, and non-concentric shrinkage patterns after NAC were risk factors for DFS, whereas a greater increase in ADC value was a protective factor. Incorporating oedema and shrinkage patterns into traditional MRI features improved the predictive performance for treatment response (AUC from 0.76-0.78 to 0.80-0.83) and DFS (C-index from 0.67-69 to 0.75-0.80). CONCLUSIONS: Oedema is an unfavorable predictor for treatment response and survival outcomes, while shrinkage patterns contribute more to the prognostic value, both of which could offer supplementary benefits for clinical outcomes in luminal BC.

[Impact of changes in malignant tumor death spectrum on life expectancy in Tianjin residents from 1999-2019].

Objective: To analyze the effects of changes in the spectrum of deaths from malignant tumors on the life expectancies of residents of different ages, sexes, and regions (urban or rural) in Tianjin from 1999 to 2019. Methods: The Abridged Life Table method and the Arriaga's decomposition method were used to calculate the effects of changes in spectrum of deaths from malignant tumors on the life expectancies of Tianjin residents of different ages, sexes, and regions. Results: During 1999-2019, the life expectancies increased by 4.96 years and 5.69 years for males and females, respectively, in Tianjin. The decreases in the mortalities from malignant neoplasms contributed 0.12 year (3.30%) and 0.03 year (0.77%) for males and females, respectively, to the increase during 1999-2007, and 0.05 year (3.13%) and 0.12 year (6.08%) for males and females, respectively, during 2007-2019. The decreases in the mortality rates of malignant tumors contributed the most to the increase among residents in the 60-69 years group, and the decreases in mortality rates of lung, gastric, esophageal, and liver cancers had relatively larger contribution. Lung cancer had a negative effect on the life expectancies of men and rural residents, but a positive effect on those of women and urban residents. The significant increases in the mortality rates of lung, colorectal, and pancreatic cancers in the ≥85 years group had a large negative effect on the overall life expectancy. Breast and ovarian cancers contributed negatively to the life expectancy of female residents. Conclusion: The overall increase in the life expectancy in Tianjin from 1999 to 2019 was mainly attributed to the elderly and the decreases in the mortality rates of gastric, esophageal, and liver cancers, among other malignancies, while the increases in the mortality rates of lung, colorectal, gallbladder, pancreatic, and breast cancers were the most significant factors hindering the increase of the life expectancy in Tianjin.

[A real-world study on the features of postpartum hepatitis flares in pregnant women with chronic HBV infection].

Objective: To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection. Methods: A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data. Results: A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z = -1.981, P = 0.048), aspartate aminotransferase (AST, z = -3.956, P < 0.001), HBV load (z = -15.292, P < 0.001), and HBeAg (z = -4.77, P < 0.001) at delivery in patients who received medication and those who did not. All patients ALT, AST, total bilirubin, direct bilirubin, and albumin showed an upward trend within six weeks after delivery. A total of 231 cases developed hepatitis within 48 weeks after delivery. Among them, 173 cases first showed ALT abnormalities within six weeks postpartum. Conclusion: Hepatitis flare incidence peaked six weeks after delivery or six weeks after drug withdrawal in pregnant women with chronic HBV infection.

[Clinical and genotypic analysis of hereditary spherocytosis combined with cholestasis among pediatric patients].

Objective: To understand the clinical and genetic characteristics of hereditary spherocytosis (HS) combined with cholestasis among pediatric patients. Methods: 12 cases of HS children accompanied by cholestasis at Hunan Children's Hospital were selected as the research subjects between January 2013 and December 2022. Clinical data were collected. Whole-exome sequencing was performed by second-generation sequencing. Suspected pathogenic mutation sites were verified by Sanger sequencing. Results: All pediatric patients were admitted to the hospital due to their yellow skin tone. Eight cases (66.67%) had a positive family history. The clinical manifestations were jaundice, splenomegaly (12/12), abdominal pain, anemia (4/12), and hepatomegaly (5/12). All pediatric patients had decreased hemoglobin, an increased reticulocyte ratio, total bilirubin and direct bilirubin, a positive erythrocyte fragility test, and remarkable spherical erythrocytes in their peripheral blood. Seven cases had elevated aminotransferase; four cases had severely elevated aminotransferase and bilirubin; eight cases had biliary calculi; and two cases had a dilated biliary tract. Liver pathological examination showed mild damage to the liver cells (G1S1) in three pediatric cases. Five children had a total of six unreported mutations: SPTB gene c.2431_2450del, c.4974-2A > G, c.2575G > A, and exon 22-35 deletion; ANK1 gene: c.2379-2380delC; and c .6dupC. Children still had abnormal bilirubin levels following treatment. Two pediatric cases underwent splenectomy. Bilirubin and hemoglobin levels returned to normal after surgery. Conclusion: Children with HS may experience cholestasis, and those with poor treatment results may consider undergoing a splenectomy. Six new types of variants have expanded the HS gene mutation spectrum.

[Efficacy of alcohol septal ablation in mildly symptomatic or severely symptomatic patients with hypertrophic obstructive cardiomyopathy].

Objective: To compare the prognosis of mildly or severely symptomatic patients with obstructive hypertrophic cardiomyopathy (OHCM) who underwent alcohol septal ablation (ASA). Methods: This retrospective study cohort consisted of patients with OHCM who received ASA treatment in Beijing Anzhen Hospital, Capital Medical University from March 2001 to August 2021. These patients were divided into mildly and severely symptomatic groups according to the severity of clinical symptoms. Long-term follow-up was conducted, and the following data were collected: duration of follow-up, postoperatire treatment, New York Heart Association (NYHA) classification, arrhythmia events and pacemaker implantation, echocardiographic parameters, and cause of death. Overall survival and survival free from OHCM-related death were observed, and the improvement of clinical symptoms and resting left ventricular outflow tract gradient (LVOTG) and the incidence of new-onset atrial fibrillation were evaluated. The Kaplan-Meier method and log-rank test were used to determine and compare the cumulative survival rates of the different groups. Cox regression analysis models were used to determine predictors of clinical events. Results: A total of 189 OHCM patients were included in this study, including 68 in the mildly symptomatic group and 121 in the severely symptomatic group. The median follow-up of the study was 6.0 (2.7, 10.6) years. There was no statistical difference in overall survival between the mildly symptomatic group (5-year and 10-year overall survival were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year overall survival were 94.2% and 83.9%, respectively, P=0.405); there was also no statistical difference in survival free from OHCM-related death between the mildly symptomatic group (5-year and 10-year survival free from HCM-related death were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year survival free from HCM-related death were 95.2% and 92.6%, respectively, P=0.846). In the mildly symptomatic group, NYHA classification was improved after ASA (P<0.001), among which 37 patients (54.4%) were in NYHA class Ⅰ, and the resting left ventricular outflow tract gradient (LVOTG) decreased from 67.6 (42.7, 90.1) mmHg (1 mmHg=0.133 kPa) to 24.4 (11.7, 35.6) mmHg (P<0.001). In severely symptomatic group, NYHA classification was also improved post ASA (P<0.001), among which 96 patients (79.3%) improved by at least one NYHA classification, and the resting LVOTG decreased from 69.6 (38.4, 96.1) mmHg to 19.0 (10.6, 39.8) mmHg (P<0.001). The incidence of new-onset atrial fibrillation was similar between the mildly and severely symptomatic groups (10.2% vs. 13.3%, P=0.565). Cox multivariate regression analysis showed that age was an independent predictor of all-cause mortality in OHCM patients post ASA (HR=1.068, 95%CI 1.002-1.139, P=0.042). Conclusions: Among patients with OHCM treated with ASA, overall survival and survival free from HCM-related death were similar between mildly symptomatic group and severely symptomatic group. ASA therapy can effectively relieve resting LVOTG and improve clinical symptoms in mildly or severely symptomatic patients with OHCM. Age was an independent predictor of all-cause mortality in OHCM patients post ASA.

Impacts of arsenic on Rad18 and translesion synthesis.

Arsenite interferes with DNA repair protein function resulting in the retention of UV-induced DNA damage. Accumulated DNA damage promotes replication stress which is bypassed by DNA damage tolerance pathways such as translesion synthesis (TLS). Rad18 is an essential factor in initiating TLS through PCNA monoubiquitination and contains two functionally and structurally distinct zinc fingers that are potential targets for arsenite binding. Arsenite treatment displaced zinc from endogenous Rad18 protein and mass spectrometry analysis revealed arsenite binding to both the Rad18 RING finger and UBZ domains. Consequently, arsenite inhibited Rad18 RING finger dependent PCNA monoubiquitination and polymerase eta recruitment to DNA damage in UV exposed keratinocytes, both of which enhance the bypass of cyclobutane pyrimidine dimers during replication. Further analysis demonstrated multiple effects of arsenite, including the reduction in nuclear localization and UV-induced chromatin recruitment of Rad18 and its binding partner Rad6, which may also negatively impact TLS initiation. Arsenite and Rad18 knockdown in UV exposed keratinocytes significantly increased markers of replication stress and DNA strand breaks to a similar degree, suggesting arsenite mediates its effects through Rad18. Comet assay analysis confirmed an increase in both UV-induced single-stranded DNA and DNA double-strand breaks in arsenite treated keratinocytes compared to UV alone. Altogether, this study supports a mechanism by which arsenite inhibits TLS through the altered activity and regulation of Rad18. Arsenite elevated the levels of UV-induced replication stress and consequently, single-stranded DNA gaps and DNA double-strand breaks. These potentially mutagenic outcomes support a role for TLS in the cocarcinogenicity of arsenite.

Association of prenatal renal ultrasound abnormalities with pathogenic copy number variants in a large Chinese cohort.

OBJECTIVES: To assess the clinical utility of prenatal chromosomal microarray analysis (CMA) in fetuses with abnormal renal sonographic findings, and to evaluate the association of pathogenic or likely pathogenic copy number variants (P/LP CNVs) with different types of renal abnormality. METHODS: This was a retrospective study of fetuses at 14-36 weeks screened routinely for renal and other structural abnormalities at the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. We retrieved and analyzed data from fetuses with abnormal renal sonographic findings, examined between January 2013 and November 2019, which underwent CMA analysis using tissue obtained from chorionic villus sampling (CVS), amniocentesis or cordocentesis. We evaluated the CMA findings according to type of renal ultrasound anomaly and according to whether renal anomalies were isolated or non-isolated. RESULTS: Ten types of renal anomaly were reported on prenatal ultrasound screening, at a mean ± SD gestational age of 24.9 ± 4.8 weeks. The anomalies were diagnosed relatively late in this series, as 64% of cases with an isolated renal anomaly underwent cordocentesis rather than CVS. Fetal pyelectasis was the most common renal ultrasound finding, affecting around one-third (34.32%, 301/877) of fetuses with a renal anomaly, but only 3.65% (n = 11) of these harbored a P/LP CNV (comprising: isolated cases, 2.37% (4/169); non-isolated cases, 5.30% (7/132)). Hyperechogenic kidney was found in 5.47% (n = 48) of fetuses with a renal anomaly, of which 39.58% (n = 19) had a P/LP CNV finding (comprising: isolated cases, 44.44% (16/36); non-isolated cases, 25.00% (3/12)), the highest diagnostic yield among the different types of renal anomaly. Renal agenesis, which accounted for 9.92% (n = 87) of all abnormal renal cases, had a CMA diagnostic yield of 12.64% (n = 11) (comprising: isolated cases, 11.54% (9/78); non-isolated cases, 22.22% (2/9); unilateral cases, 11.39% (9/79); bilateral cases, 25.00% (2/8)), while multicystic dysplastic kidney (n = 110), renal cyst (n = 34), renal dysplasia (n = 27), crossed fused renal ectopia (n = 31), hydronephrosis (n = 98), renal duplication (n = 42) and ectopic kidney (n = 99) had overall diagnostic rates of 11.82%, 11.76%, 7.41%, 6.45%, 6.12%, 4.76% and 3.03%, respectively. Compared with the combined group of CMA-negative fetuses with any other type of renal anomaly, the rate of infant being alive and well at birth was significantly higher in CMA-negative fetuses with isolated fetal pyelectasis or ectopic kidney, whereas the rate was significantly lower in fetuses with isolated renal agenesis, multicystic dysplastic kidney or severe hydronephrosis. The most common pathogenic CNV was 17q12 deletion, which accounted for 30.14% (22/73) of all positive CMA findings, with a rate of 2.51% (22/877) among fetuses with an abnormal renal finding. Fetuses with 17q12 deletion exhibited a wide range of renal phenotypes. Other P/LP CNVs in the recurrent region that were associated with prenatal renal ultrasound abnormalities included 22q11.2, Xp21.1, Xp22.3, 2q13, 16p11.2 and 1q21, which, collectively, accounted for 2.17% (19/877) of the fetuses with prenatal renal anomalies. CONCLUSIONS: In this retrospective review of CMA findings in a large cohort of fetuses with different types of renal ultrasound abnormality, the P/LP CNV detection rate varied significantly (3.03-39.58%) among the different types of kidney anomaly. Our data may help in the decision regarding whether to perform prenatal genetic testing in fetuses with renal ultrasound findings. Specifically, prenatal CMA testing should be performed in cases of hyperechogenic kidney, regardless of whether or not the anomaly is isolated, while it should be performed postnatally rather than prenatally in cases of fetal pyelectasis. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

[Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors].

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

[Phenotypic and genomic characterization for Salmonella isolates recovered from meat products in Beijing wholesale markets, 2014-2015].

Objective: To analyze the phenotypic and genomic characteristics of Salmonella isolates recovered from meat products in Beijing wholesale markets. Methods: A total of 336 Salmonella strains from meat products collected from wholesale markets in Beijing were tested for antimicrobial resistance to 25 antimicrobial compounds by micro-broth dilution method; whole genome data were sequenced, followed by the serotype and ST type prediction by Seqsero2 and SISTR software, and the drug resistance genes and virulence factors were also predicted with CARD and VFDB databases of Abricate software; Salmonella serotyping assay kit and serum agglutination method were used for serotype confirmation of some isolates with different genome prediction results. Results: The resistance rates to Nalidixic acid and Ampicillin were 62.5% (210/336) and 55.1% (185/336), respectively, and all isolates were susceptible to Tigecyclin, Cefoxitin and Carbapenem antimicrobial compounds; 207 isolates (61.6%, 207/336) were multi-drug resistant, some could even be resistant to ten categories of drugs at the same time, and the most common antimicrobial resistance spectrum was NAL-AMP-SAM. A total of 24 serotypes were detected with predominant serotypes of Enteritidis (34.5%, 116/336), Derby (17.3%, 58/336) and Indiana (10.4%, 35/336). A total of 27 ST types were detected, the dominant type was ST11; ST types were in good consistency with serotypes; The detection rates of resistant genes referred to aminoglycosides, fluoroquinolones, ß-lactams, sulfonamides and tetracyclines are more than 48%, and the first two reached 100%. The prediction of drug resistance genes was consistent with the results of antimicrobial resistance phenotype. A total of 122 virulence genes were predicted, 74 of which existing among all isolates. Conclusion: Salmonella in meat from the wholesale markets of Beijing has a high proportion of multiple drug resistance, a complex drug resistance spectrum, a variety of serotypes and ST types, and a high carrying rate of drug resistance gene and virulence gene; drug resistance phenotype and genotype are relatively consistent.

[Study on the diagnostic value of transient elastography, APRI and FIB-4 for liver fibrosis in children with non-alcoholic fatty liver disease].

Objective: To evaluate the diagnostic value of transient elastography, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) for liver fibrosis in children with non-alcoholic fatty liver disease (NAFLD). Methods: A retrospective study was conducted on 100 cases of nonalcoholic fatty liver disease in Hunan Children's Hospital between August 2015 to October 2020 to collect liver tissue pathological and clinical data. The receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic value of liver stiffness measurement (LSM), APRI and FIB-4 in the diagnosis of different stages of liver fibrosis caused by NAFLD in children. Results: The area under the ROC curve (AUC) value of LSM, APRI and FIB-4 for diagnosing liver fibrosis (S≥1) were 0.701 [95% confidence interval (CI): 0.579 ~ 0.822, P = 0.011], 0.606 (95%CI: 0.436 ~ 0.775, P = 0.182), and 0.568 (95%CI: 0.397 ~ 0.740, P = 0.387), respectively. The best cut-off values were 6.65 kPa, 21.20, and 0.18, respectively. The AUCs value of LSM, APRI, and FIB-4 for diagnosing significant liver fibrosis (S≥ 2) were 0.660 (95% CI: 0.552 ~ 0.768, P = 0.006), 0.578 (95% CI: 0.464 ~ 0.691, P = 0.182) and 0.541 (95% CI: 0.427 ~ 0.655, P = 0.482), respectively. The best cut-off values were 7.35kpa, 24.78 and 0.22, respectively. The AUCs value of LSM, APRI and FIB-4 for the diagnosis of advanced liver fibrosis (S≥ 3) were 0.639 (95% CI: 0.446 ~ 0.832, P = 0.134), 0.613 (95% CI: 0.447 ~ 0.779, P = 0.223) and 0.587 (95% CI: 0.411 ~ 0.764, P = 0.346), respectively. The best cut-off values were 8.55kpa, 26.66 and 0.27, respectively. Conclusion: The transient elastography technique has a better diagnostic value than APRI and FIB-4 for liver fibrosis in children with NAFLD.

[Therapeutic effects of alcohol septal ablation in mildly symptomatic patients with hypertrophic obstructive cardiomyopathy].

Objective: To observe the therapeutic effects of alcohol septal ablation (ASA) in mildly symptomatic patients (NYHA class Ⅱ) with hypertrophic obstructive cardiomyopathy(HOCM). Methods: This retrospective study included 150 mildly symptomatic patients with HOCM hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from March 2001 to December 2017, consisting of medical therapy group (n=102) and ASA group (n=48). Baseline clinical data were collected, patients were followed up to a mean of 6.0 (3.5, 8.1) years. Overall and HCM-related mortality events (including chronic heart failure, atrial fibrillation related stroke, sudden cardiac death) were observed in the two groups. Moreover, the improvement of NYHA function classification and left ventricular outflow tract gradient (LVOTG) were also evaluated. Survival analysis was performed by Kaplan-Meier method. Results: Age of this cohort was (52.9±14.5)years, 92 cases(61.3%) were male. In the follow-up, LVOTG was reduced from (85.8±35.4)mmHg (1 mmHg=0.133 kPa) to (27.7±19.8)mmHg (P<0.001) in the ASA group, and from (66.3±35.0)mmHg to (56.5±27.7)mmHg in medical therapy group(P<0.01). At the last clinical follow-up, there were 32 patients (66.7%) whose LVOTG were<30 mmHg, septal thickness decreased from (20.3±3.8)mm to (16.1±3.4)mm (P<0.001), NYHA classification was also remarkably improved (P<0.001). New-onset atrial fibrillation tended to be lower in the ASA group compared to medical therapy group (9.3%(4/43) vs. 20.8%(20/96),P=0.096). Eleven patients (10.8%) in the medical therapy group and 2 patients (4.2%) in the ASA group died during the follow-up. One patient received pacemaker during the peri-procedural period, 1 patient was implanted with two-chamber pacemaker due to Ⅲ° atrioventricular block at 10 years after operation in the ASA group. Survival free of all-cause mortality of ASA group at 5 and 10 years was 97.9% and 97.9%, respectively, which was comparable to the medical therapy group (P=0.231). Survival free of HCM-related mortality was similar between the two groups (P=0.397). Conclusions: Compared with medical therapy in mildly symptomatic patients with HOCM, long-term survival rate is similar after ASA. Meanwhile, ASA can remarkably reduce LVOTG and improve the clinical status of the patients. Therefore, ASA may be used as an alternative therapy for mildly symptomatic HOCM patients.

Nomogram predicting early neurological improvement in ischaemic stroke patients treated with endovascular thrombectomy.

BACKGROUND AND PURPOSE: Early neurological improvement (ENI) after endovascular thrombectomy (EVT) has been associated with favorable outcomes. This study aimed to identify the optimal definition of ENI and develop a nomogram for predicting ENI after EVT in acute ischaemic stroke. METHODS: Patients with EVT were enrolled from a multicenter registry as the training cohort. The receiver operating characteristic curve was used to estimate the optimal threshold for ENI at 24 h of EVT. Logistic regression analysis was utilized to generate the best-fit nomogram for predicting ENI. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC). An additional 447 patients from two stroke centers were prospectively recruited as the test cohort for validating the nomogram. RESULTS: A total of 612 patients with EVT were included in the training cohort. The optimal threshold for predicting 3-month favorable outcome (modified Rankin Scale 0-2) was an improvement of the National Institutes of Health Stroke Scale (NIHSS) score by ≥6 points (AUC 0.875; sensitivity 79.5%; specificity 90.7%). Age, blood glucose, recanalization, symptomatic intracranial hemorrhage (sICH) and baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) were independently associated with ENI, and were incorporated in the nomogram. The AUC of the nomogram was 0.795 in the training cohort and 0.752 in the test cohort. CONCLUSIONS: A reduction of NIHSS score ≥6 appeared to be the optimal definition of ENI. The nomogram composed of age, blood glucose, recanalization, sICH and baseline ASPECTS may predict the probability of ENI in ischaemic stroke patients treated with EVT.

[Epidemiology and influencing factors of human immunodeficiency virus and hepatitis B virus co-infected patients in Beijing].

Objective: To analyze the epidemiological characteristics of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infected patients in Beijing and investigate the associated factors. Methods: The clinical data of patients with HIV infection who were treated in HIV/AIDS designated hospitals (Peking Union Medical College Hospital, Beijing Ditan Hospital and Beijing Youan Hospital) were retrospectively analyzed. Results: A total of 11 572 patients were finally included in the study, among whom 532 patients (4.6%) were co-infected with HIV and HBV. Most of the co-infected patients were young male adults (28~48 years old), accounting for 85.9%. The main transmission route was homosexual behavior (74.8%). There were 87.4% co-infected patients treated with two anti-HBV drugs, including lamivudine (3TC) and tenofovir (TDF). From 2013 to 2018, the annual prevalence of HIV and HBV co-infection decreased gradually, with the rate of 6.37%, 4.55%, 3.92%, 4.68%, 4.24% and 2.74%, respectively. In our study, The main influencing factors of HIV and HBV co-infection were age older than 28 years old versus<28 years old (OR=2.807, 95%CI 1.241-6.345) and marriage status (married versus unmarried, OR=1.259, 95%CI 1.004-1.579). Conclusions: The proportion of HBV infection in HIV-infected patients is 4.60% (532) in our cohort. From 2013 to 2018, the prevalence of HIV and HBV co-infection in Beijing shows a decreasing trend. The risk of co-infection is higher in married young adults (28~48 years old).

[Early constant observation of the effect of deferoxamine mesylate on improvement of vascularized bone regeneration in SD rat skull critical size defect model].

OBJECTIVE: To investigate the effect of local administration of deferoxamine mesylate (DFO) on vascularization and osteogenesis and its ability to maintain the activity of hypoxia inducible factor-1α (HIF-1α), by constantly observing early changes of vessel-like structures and bone tissues during bone defects healing. METHODS: Skull critical bone defect models were constructed on a total of thirty male SD rats (6-8 weeks old). The rats were randomly divided into experimental group (DFO group) or control group (normal saline group). 300 µL 200 µmol/L DFO solution or normal saline was locally injected on the 4th day after the defect was made. On the 5th, 7th, 10th, 14th, and 28th days after surgery, three rats in each group were sacrificed respectively. HE staining and Masson staining were performed to observe new bone formation and mineralization. HIF-1α immunohistochemistry staining was performed to examine relative expression of protein. Qualitative analysis and comparation were performed by t-tests on relative expression of HIF-1α, numbers of blood vessels and percentages of mineralization tissues of new bone areas. RESULTS: On the 5th, 7th, 10th, 14th and 28th days after surgery, the average numbers of blood vessels were 30.40±12.15, 62.00±17.87, 73.43±15.63, 40.00±7.84, 48.71±11.64 in the DFO group, and 18.75±6.63, 19.13±2.80, 51.35±16.21, 27.18±7.32, 30.88±13.43 in the control group. The number of blood vessels in the DFO group was significantly higher than that of the control group at each time point (P < 0.05). The mass of new bone in the DFO group was higher than that in the control group on the 14th and 28th days after surgery. The percentage of mineralization tissues of new bone area on the 14th and 28th days after injection were (27.73±5.93)% and (46.53±3.66)% in the DFO group, and (11.99±2.02)% and (31.98±4.22)% in the control group. The percentage of mineralization tissues in the DFO group was significantly higher than that of the control group at each time point (P < 0.001). The relative expression of HIF-1α in the DFO group compared with the control group was 2.86±0.48, 1.32±0.26, 1.32±0.32, 1.28±0.38 and 1.05±0.34 on the 5th, 7th, 10th, 14th and 28th days, with significant expression difference on the 5th day (P < 0.01). CONCLUSION: Use of DFO in bone defects promotes vascularization and osteogenesis in the defect area, and maintains the protein activity of HIF-1α temporarily.

Effect of additive-assisted fat transplantation on fat graft survival rate: A preliminary experimental study based on a rabbit animal model.

BACKGROUND: Improving the survival rate of fat grafts is yet a difficult problem in the field of autologous fat transplantation. Prevailing methods such as making nanofat and SVF are time-consuming. Hence, the role of additives application in the improvement of fat graft survival during fat transplantation was considered and preliminarily evaluated in a rabbit animal model. METHODS: A rabbit animal model was established where rabbit ears were injected with a mixture of 1.5mL of adipose tissue and 1mL of saline (group A), 1.5mL of adipose tissue and 1mL of botulinum toxin A (BoNTA) (group B), 1.5mL of adipose tissue and 1mL of prostaglandin E2 (groupC), 1.5mL of adipose tissue and 1mL of PDRN (group D) respectively. Then, the extents of neovascularization and inflammation were evaluated on the 7th, 14th, 28th, 42nd, 56th and 70th day after injection by ELISA assays and H&E and immunofluorescence staining. RESULTS: The results showed that pre-treatment with BoNTA, prostaglandin E2 and PDRN improved graft volume and weight. The H&E and immunofluorescence staining revealed that BoNTA, prostaglandin E2 and PDRN improved the graft angiogenesis. Simultaneously, TNF-α expression level detected by ELISA was the lowest in the PDRN group. CONCLUSION: Henceforth, the present preliminary study suggests that pre-transplantation treatment with BoNTA, prostaglandin E2 and PDRN can improve the fat graft angiogenesis and graft integrity, whereby the effect of adding PDRN may be significant.

[Simultaneous combined radical surgery for hepatic and renal alveolar echinococcosis: an analysis of 10 clinical cases].

Objective: To examine the feasibility, safety and efficacy of simultaneous combined radical surgery for hepatic and renal alveolar echinococcosis (AE). Methods: Clinical dates of consecutive 10 hepatic and renal AE patients who accepted surgical treatment in the First Affiliated Hospital of Xinjiang Medical University during April 2013 to September 2019 were analyzed retrospectively. There were 8 males and 2 females, aged (42.5±10.3) years (range: 27 to 52 years). Seven of them had previously palliative surgical treatment with poor compliance to post-operative medication. All of the patients had hepatic-renal combined AE lesions, and two of them had left lateral and left renal lesions for each, which sized for (726.4±576.1)cm3 (range: 117.0 to 1 998.0 cm3). Extra-hepatic or renal lesions infiltrated to right diaphragm, inferior vena cava, right adrenal gland, abdominal wall, right psoas muscle, duodenum wall and right pulmonary lobe (respectively were 7, 7, 6, 2, 1, 1, 2 cases). Surgery were performed mainly with simultaneous combined surgery and vascular reconstruction techniques for this series. Hemi-hepatectomy or extended right lobectomy was applied in 8 patients, while 2 other patients received ex vivo liver resection and autotransplantation, additionally, one patient had partial hepatectomy for left lateral lobular lesion. Total right nephrectomy, partial right nephrectomy and partial left nephrectomy were respectively performed on 7, 3 and 1 patient(s). Additionally, extra-hepatic or renal lesions were eradicated followed by relevant repairments or reconstructions. Results: Surgeries went well and there was no intra-or post-operative liver or renal dysfunction occurred. During recovery period, 3 cases experienced with hydrothorax and managed well after drainage and supportive treatment, and one patient developed peri-renal urinary leakage and cured by "J" catheter. The subjects were followed-up for 6 to 81 months (median: 21 months), no death, organ dysfunction, chronic or acute kidney diseases occurred. One case encountered with abdominal hernia at post-operative 7th month and was successfully managed with laparoscopic repair with artificial mesh. No disease recurrence in all patients, which reached clinical cure at last. Conclusion: When complied strictly to indications, simultaneous combined radical surgery could be a feasible, safe and efficient approach for patients with hepatic and renal AE, which is primary or relapsed from previous hepatic AE surgery or interventional therapies as well as neighboring organ AE invasions.

Clinical characteristics and predictors of the duration of SARS-CoV-2 viral shedding in 140 healthcare workers.

BACKGROUND: Epidemiological and clinical features of patients with COVID-19 have been reported, but none of them focused on medical staff, and few predictors of the duration of viral shedding have been reported. It is urgent to help healthcare workers prevent and recover quickly from the coronavirus disease 2019 (COVID-19). METHODS: We enrolled 140 medical workers with COVID-19 in Wuhan. Epidemiological, demographic, clinical, laboratory, radiological treatment and clinical outcome data were collected, and predictors of the duration of viral shedding were explored through multivariable linear regression analysis. RESULTS: The medical staff with COVID-19 presented mild clinical symptoms and showed a low frequency of abnormal laboratory indicators. All the medical staff were cured and discharged, of whom 96 (68.6%) were female, 39 (27.9%) had underlying diseases, the median age was 36.0 years, and 104 (74.3%) were infected whilst working in hospital. The median duration of viral shedding was 25.0 days (IQR:20.0-30.0). Multivariable linear regression analysis showed reducing viral shedding duration was associated with receiving recombinant human interferon alpha (rIFN-α) treatment, whilst the prolonged duration of viral shedding correlated with the use of glucocorticoid treatment, the durations from the first symptom to hospital admission and the improvement in chest computed tomography (CT) evidence. Moreover, infected healthcare workers with lymphocytes less than 1.1 × 109 /L on admission had prolonged viral shedding. CONCLUSION: Medical staff with timely medical interventions show milder clinical features. Glucocorticoid treatment and lymphocytes less than 1.1 × 109/L are associated with prolonged viral shedding. Early admission and rIFN-α treatment help shorten the duration of viral shedding.

Abnormal processing of IL-1ß in NLRP7-mutated monocytes in hydatidiform mole patients.

NOD-like receptor pyrin 7 (NLRP7) has been identified as the major gene responsible for the recurrent hydatidiform mole (RHM). The immunological role of NLRP7 mutation in HM patients has not been conclusively demonstrated. Hence, we aim to demonstrate this role in our study. We followed 12 new patients with NLRP7 non-synonymous variations (NSVs) from date to date. Peripheral blood mononuclear cells (PBMCs) were collected separately from patients with and without NLRP7 mutation. Supernatant interleukin (IL)-1ß secretion, intracellular pro-IL-1ß and mature IL-1ß expressions were measured after 24 h lipopolysaccharide (LPS) stimulation. Plasmids with corresponding NSVs were generated to evaluate the ability of processing pro-IL-1ß into mature IL-1ß in vitro. Homozygous or compound heterozygous NLRP7 mutations secreted less IL-1ß in roots of abnormal intracellular pro-IL-1ß or mature IL-1ß, according to different domains. Plasmids with NSVs could also affect processing or/and trafficking together with caspase-1 and apoptosis-associated speck-like protein (ASC). Inflammasome-related NLRP7 mutation is a potential mechanism of RHM.

Demographic and clinical factors associated with immune reconstitution in HIV/HBV co-infected and HIV mono-infected patients: a retrospective cohort study.

OBJECTIVES: To describe the clinical characteristics and factors associated with CD4 T-cell count and CD4/CD8 ratio restoration in HIV mono-infected and HIV/HBV co-infected individuals, and to explore liver and renal functional changes in both groups. METHODS: A retrospective cohort study was performed including 356 HIV/HBV co-infected and 716 HIV mono-infected participants who initiated antiretroviral therapy (ART) during 2013-2017 in Beijing Youan Hospital, China. Demographic and clinical characteristics were compared between the two groups, using χ2 and Mann-Whitney non-parametric tests. Bivariate and multivariate Cox regression models were used to test their association. RESULTS: Baseline HIV viral load and ART regimen were found to be significantly associated with CD4 T-cell restoration among HIV-infected participants, whereas baseline HIV viral load was the only significant factor associated with CD4 T-cell restoration in HIV/HBV co-infected participants. The final model showed that baseline HIV viral load and ART regimen were significantly associated with CD4/CD8 ratio restoration among HIV-infected participants, while baseline HIV viral load was the significant factor. Liver and renal functions were similar at the endpoint (P > 0.05). CONCLUSIONS: Baseline HIV viral load count was found to be the key factor affecting immune restoration in both HIV and HIV/HBV individuals. Future multi-wave prospective studies are needed to clarify the potential biological mechanism.

A novel nomogram to predict early neurological deterioration in patients with acute ischaemic stroke.

BACKGROUND AND PURPOSE: Acute ischaemic stroke (AIS) is a vital cause of mortality and morbidity in China. Many AIS patients develop early neurological deterioration (END). This study aimed to construct a nomogram to predict END in AIS patients. METHODS: Acute ischaemic stroke patients in Nanjing First Hospital were recruited as the training cohort. Additional patients in Nantong Third People's Hospital were enrolled as the validation cohort. Multivariate logistic regression was utilized to establish the nomogram. Discrimination and calibration performance of the nomogram were tested by concordance index and calibration plots. Decision curve analysis was employed to assess the utility of the nomogram. RESULTS: In all, 1889 and 818 patients were recruited in the training and validation cohorts, respectively. Age [odds ratio (OR) 1.075; 95% confidence interval (CI) 1.059-1.091], diabetes mellitus (OR 1.673; 95% CI 1.181-2.370), atrial fibrillation (OR 3.297; 95% CI 2.005-5.421), previous antiplatelet medication (OR 0.473; 95% CI 0.301-0.744), hyper-sensitive C-reactive protein (OR 1.049; 95% CI 1.036-1.063) and baseline National Institutes of Health Stroke Scale (OR 1.071; 95% CI 1.045-1.098) were associated with END and incorporated in the nomogram. The concordance index was 0.826 (95% CI 0.785-0.885) and 0.798 (95% CI 0.749-0.847) in the training and validation cohorts. By decision curve analysis, the model was relevant between thresholds of 0.06 and 0.90 in the training cohort and 0.08 and 0.77 in the validation cohort. CONCLUSIONS: The nomogram composed of hyper-sensitive C-reactive protein, age, diabetes mellitus, atrial fibrillation, previous antiplatelet medication and baseline National Institutes of Health Stroke Scale may predict the risk of END in AIS patients.