Peritumoural MRI radiomics signature of brain metastases can predict epidermal growth factor receptor mutation status in lung adenocarcinoma.

AIM: To investigate whether magnetic resonance imaging (MRI) radiomics features of brain metastases (BMs) can predict epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma. MATERIALS AND METHODS: Between June 2014 and December 2022, 58 histopathologically confirmed lung adenocarcinoma patients (27 with EGFR wild-type, 31 with EGFR mutation) who underwent gadobenate dimeglumine-enhanced brain MRI were recruited retrospectively. A total of 123 metastatic brain lesions were allocated randomly into the training cohort (n=86) and test cohort (n=37) at a ratio of 7:3. Radiomics models based on multi-sequence MRI images in different regions such as volume of interest (VOI)enhancing tumour, VOIwholetumour, VOIperitumour 1mm, VOIperitumour 3mm, and VOIperitumour 5mm were built. The optimal radiomics model was integrated into the clinical or radiological indicators to construct a fusion model through multivariable logistic regression analysis. RESULTS: The optimal radiomics model based on the VOIperitumour 1mm, a combination of nine features selected from the fluid-attenuated inversion recovery (FLAIR) sequence, yielded areas under the curves (AUCs) of >0.75 in the training and test cohorts. The prediction of the fusion model with integration of clinical factors (age) and radiomics score (the optimal radiomics model) was not better than that of the optimal radiomics model alone in the test cohort (AUC: 0.808 and 0.785, respectively, p=0.525). CONCLUSION: The FLAIR radiomics model based on VOIperitumour 1mm as an effective biomarker helps predict EGFR mutation status in lung adenocarcinoma patients with BMs and then assists clinicians in selecting optimal treatment strategies.

[Effect of adenovirus-mediated shRNA down-regulates SHP2 expression on the apoptosis of human hepatic stellate cells LX-2].

Objective: To investigate the effect of adenovirus-mediated short hairpin RNA (shRNA) downregulating SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) on the apoptosis of human hepatic stellate cells LX-2 cultured in vitro. Methods: The recombinant adenovirus Ad-shRNA/SHP2 carrying shRNA targeted SHP2 and expressing green fluorescent protein (GFP), and the empty control virus Ad-GFP expressing GFP were transfected into LX-2 cells cultured in vitro. Real-time fluorescence quantitative PCR was used to detect SHP2 mRNA expression in LX-2 cells. Western blot was used to detect the protein expressions of SHP2, Bax, and Bcl-2 in LX-2 cells. TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry were used to detect apoptosis in LX-2 cells. Experimental group: (1) Control group: LX-2 cells were transfected with DMEM instead of adenovirus; (2) Ad-GFP group: transfected with empty virus Ad-GFP; (3) Ad-shRNA/SHP2 group: transfected with recombinant adenovirus Ad-shRNA/SHP2. The means between multiple groups were compared using a one-way ANOVA and the LSD test was used for inter group comparisons. Results: shRNA-targeted SHP2 significantly down-regulated the expression of SHP2 protein and mRNA in LX-2 cells (P < 0.05). The TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry results showed that the apoptosis rate of LX-2 cells in the Ad-shRNA/SHP2 group (12.755%±1.606%, 19.340%±2.505%) (P < 0.05) was significantly higher compared to the control group (3.077%±0.731%, 9.438%±0.804%) and the Ad-GFP group (3.250%±0.851%, 8.893%±1.982%), with no statistically significant difference between the control group and the Ad-GFP group (P > 0.05). Western blot analysis of Bax and Bcl-2 protein expression in LX-2 cells of each group revealed that the Bax protein expression was significantly higher in the Ad shRNA/SHP2 group (2.493 ± 0.203) (P < 0.05) compared to the control group and Ad-GFP group (1.989 ± 0.147, 1.999 ± 0.162), with no statistically significant difference between the control group and the Ad-GFP group (P > 0.05), while the Bcl-2 protein was significantly decreased in the Ad-shRNA/SHP2 group (1.042±0.148) compared with the control group and the Ad-GFP group (1.707±0.146, 1.521±0.142), with no statistically significant difference between the control group and the Ad-GFP group (P > 0.05). Conclusions: SHP2 expression down-regulation induces apoptosis of human hepatic stellate cells LX-2 in vitro by reducing Bcl-2/Bax.

[Molecular characteristics of ciprofloxacin-cefotaxime-azithromycin co-resistant Salmonella enterica Serovar Thompson in foodborne diseases in Hunan Province].

Objective: To investigate the molecular characteristics of ciprofloxacin-cefotaxime-azithromycin co-resistant Salmonella enterica serovar Thompson (S. Thompson) isolates from sporadic cases of foodborne diseases and aquatic foods in Hunan province. Methods: Ciprofloxacin-cefotaxime-azithromycin co-resistant S. Thompson isolates were selected from samples, and broth microdilution method was used to determine the resistance to 11 antibiotics of these isolates in vitro. Whole genome sequencing was used for investigating antimicrobial resistance gene patterns and phylogenetic relationships of strains. Results: Nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates were recovered from 19 S. Thompson isolates. Among nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates, eight of them harbored IncC plasmids, simultaneously carrying plasmid-mediated quinolone resistance (PMQR) genes qepA and qnrS1, ß-lactamase resistance gene blaCMY-2, azithromycin resistance gene mph(A), and one isolate harbored IncR plasmid, and carried PMQR genes qnrB4 and aac(6')-Ib-cr, blaOXA-10 and mph(A). Genetic environment analysis showed that qnrS1, qepA, mph(A) and blaCMY-2 genes might be integrated on genomes of strains by ISKra4, IS91, IS6100 and ISEcp1, respectively. Phylogenetic core genome comparisons demonstrated that ciprofloxacin-cefotaxime-azithromycin co-resistant isolates from patients and aquatic foods were genetically similar and clustered together. Conclusion: Ciprofloxacin-cefotaxime-azithromycin co-resistant S. Thompson isolates have been isolated from both human and aquatic food samples, suggesting that the spread of multidrug resistant Salmonella between human and aquatic animals.

[A comparative study between retro-auricular single-site endoscopic thyroidectomy and transoral endoscopic thyroidectomy vestibular approach: a single-center retrospective analysis].

Objectives: To compare the efficiacy of retro-auricular single-site endoscopic thyroidectomy (RASSET) and that of transoral endoscopic thyroidectomy vestibular approach (TOETVA). Methods: In Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, 10 patients underwent RASSET from June 2021 to August 2021, and 21 patients underwent TOETVA from January 2016 to August 2021. All the 21 patients' clinical data was analyzed retrospectively. There were 2 males and 8 females in the RASSET group, aging (48.2±13.9) years (range: 28 to 67 years). There were 5 males and 16 females in the TOETVA group, aging (31.3±8.2) years (range: 21 to 49 years). All patients underwent thyroid lobectomy. A 3 cm in length incision was cut on single auricula posterior sulci to creat the approach in the RASSET group. Then a Trocar made with of a glove was inserted. Retaining the omohyoid, the sternocleidomastoid muscle and anterior cervical muscle were pulled apart, exposing a single lobe of the thyroid gland and lymphatic tissue of zone Ⅵ, for en-bloc resection. The clinical data of the two groups were collected and analyzed by t test, Mann-Whitney U test, Fisher exact test or χ2 test. Clinical data and postoperative efficacy indexes such as operation time, postoperative C reactive protein level, and postoperative complications were recorded. Results: Compared with the TOETVA group, the operation time was longer in the RASSET group ((256.8±77.0) minutes vs. (201.2±54.9) minutes, t=2.31, P=0.028), and increase of postoperative C reaction protein (24 hours postoperative vs. preoperative) was lower in the RASSET group (8.58(13.24) mg/L vs. 46.24(48.88) mg/L, Z=-4.311, P<0.01). But there was no significant difference between the RASSET group and TOETVA group in the number of lymph nodes dissection (2(5) vs. 2(3), Z=-0.326, P=0.759). Besides, there were no complications in the RASSET group. Conclusion: Retro-auricular single-site endoscopic thyroid loectomy is easy to achieve the en-bloc resection of tumors with a well-concealed scar and less traumatic dissection.

[Associated factors of different fatigue dimensions in elderly patients with rheumatoid arthritis].

Objective: To investigate the associated factors of different dimensions of fatigue in elderly patients with rheumatoid arthritis (RA). Methods: A cross-sectional analysis was performed in the elderly outpatients with RA (age ≥ 60 years) in the First Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2019. Fatigue was measured by Multidimensional Fatigue Inventory-20 (MFI-20) and 36-item Short Form Health Survey-Vitality (SF-36-VT). Physical fatigue and mental fatigue were subsequently measured by MFI-20 subscales. Results: A total of 104 patients were included. Male-to-female ratio was 1∶3.3. The average age was (68±6) years. The MFI-20 score and SF-36-VT score were 60±14 and 64±20, respectively. The score of physical fatigue measured by MFI-20 was 14±3, and mental fatigue scored 10±4 (P<0.001). Arthralgia, disease activity, disability, insomnia, depression and anxiety were correlated with fatigue assessed by MFI-20 (correlated coefficient: 0.48-0.62). Multivariable regression analysis showed that arthralgia and depression were associated with physical fatigue (Standardized regression coefficients were 0.44 and 0.38, respectively). Insomnia, depression and anxiety were associated factors of mental fatigue (Standardized regression coefficients were 0.20, 0.32 and 0.24, respectively). Conclusions: Elderly patients with RA experiencehigh level of fatigue, mainly presenting as physical fatigue. Arthralgia and depression mainly affect physical fatigue, and arthralgia is a critical factor. Insomnia, depression and anxiety are associated with mental fatigue.

Umbilical arterial Doppler ultrasonography predicts late pregnancy outcomes in patients with lupus nephritis: a multicenter study from southern China.

OBJECTIVES: To investigate the fetal adverse pregnancy outcomes (APOs) and the predictive value of umbilical arterial Doppler ultrasonography in the third trimester in pregnant women with lupus nephritis (LN). METHODS: A retrospective cohort study enrolling 203 LN patients from 2007 to 2017 was performed. Ultrasonic parameters were recorded. RESULTS: Fetal APOs occurred in 103 patients (103/203, 50.7%). Sixty-six pregnancies (66/203, 32.5%) ended with preterm births. The incidence rate of intrauterine growth restriction (IUGR) was 18.2% (37/203). Fetal distress was noted in 23 pregnancies (23/203, 11.3%). All the Doppler parameters elevated in patients with IUGR, fetal distress, and composite conditions. Resistance index (RI) indicated the highest risk of IUGR and composite APOs. The cutoff values were 0.66 and 0.67, respectively. Sensitivities were 51.4% and 33.7%, and specificities were 87.4% and 92.1%. Peak velocity of the umbilical arteries at end-systole (Vmax, abbreviated as S) to that at end-diastole (Vmin, abbreviated as D) (S/D) ratio was also a best predictor for IUGR, with the optimal cutoff value of 2.88. Sensitivity and specificity were comparable with RI. Pulsatility index (PI) over 0.84 was an ideal indicator for fetal distress with an optimal combination of sensitivity (89.5%) and specificity (51.6%). CONCLUSIONS: Fetal complications were frequent in patients with LN. Umbilical arterial Doppler ultrasonography was a useful measure to predict late IUGR, fetal distress, and the composite APOs.

Invasive fungal disease in patients with systemic lupus erythematosus from Southern China: a retrospective study.

OBJECTIVE: To investigate the characteristics and associated factors of invasive fungal disease in patients with systemic lupus erythematosus from Southern China. METHODS: A retrospective study was performed. Demographic and clinical characteristics, laboratory data, and radiographic manifestations were recorded. RESULTS: A total of 45 lupus patients with invasive fungal disease (incidence 1.1%) were included. Twenty-three cases (51.1%) were infected with mold and 22 cases (48.9%) with yeast. Aspergillus spp. (44.4%) and Cryptococcus spp. (33.3%) were common. Aspergillosis mainly occurred in the lung. Cryptococcosis developed in the lung (40.0%), meninges (46.7%) and bloodstream (13.3%). Compared with yeast infection, mold infection tended to develop in patients with active lupus nephritis (65.2% vs. 31.8%, P = 0.03) and the mortality rate was higher (20.0% vs. 0%, P = 0.001). Co-infection with bacteria, virus or superficial fungi occurred in 12 patients (26.7%). Multivariate logistic regression analysis indicated that lymphopenia (odds ratio 2.65, 95% confidential interval 1.14-6.20, P = 0.02) and an accumulated dose of glucocorticoid (odds ratio 1.58, 95% confidence interval 1.10-2.25, P = 0.01) was associated with invasive fungal disease in lupus patients. CONCLUSION: Mold infection tended to develop in patients with active lupus disease with high mortality. Co-infection is not rare. Lymphopenia and an accumulated dose of glucocorticoid are associated with invasive fungal disease in lupus patients.

[Efficacy and safety of barbed sutures in total hip arthroplasty and total knee arthroplasty: a meta-analysis].

Objective: To appraise the clinical outcomes of barbed suture in closure of total hip and total knee arthroplasty. Methods: Databases (Web of Science, Embase, PubMed, Cochrane Controlled Trials Register,Cochrane Library,Highwire,China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI),VIP and Wanfang database) were searched for randomized controlled trials comparing barbed sutures and conventional sutures in total hip and total knee arthroplasty published before January, 2019. Finally, 11 articles (12 randomized controlled trials) involving 1 629 hips or knees were included in this study. The meta-analysis was performed using the Review Manager software. Results: Compared with conventional sutures,barbed sutures resulted in shorter total wound closure time (P<0.001), less ecchymosis and needle prick (both P<0.05).There was no significant differences in terms of wound related complications, superficial infection, stitch abscess, blister, exudation, broken sutures, range of motionand KSS between barbed sutures and conventional sutures(all P>0.05). Conclusions: Based on available level Ⅰ evidence, it indicated that knotless barbed suture maybe a better approach for wound closure in total hip and total knee arthroplasty.

[A new attempt with lipoprotein lipase agonists in the treatment of nonalcoholic steatohepatitis].

Objective: To analyze non-alcoholic steatohepatitis (NASH)-related differentially expressed genes (DEGs) by bioinformatics methods to find key pathways and potential therapeutic targets for NASH. Methods: GSE61260 chip was downloaded from the public microarray database and liver biopsy samples from 24 NASH cases and 38 healthy controls were included. The Limma software package in R language was used to screen DEGs under the condition of difference multiple > 1.5 and adj. P < 0.05. The clusterProfiler software package was used for GO analysis and KEGG analysis. The STRING online database was used for protein-protein interaction analysis, and the L1000 and DrugBank databases were used for drug prediction. Results: Compared with healthy control group, 857 DEGs were screened out in NASH group including 167 up-regulated genes and 690 down-regulated genes. GO analysis showed that DEGs were mainly involved in inflammation and cholesterol metabolism. KEGG analysis showed that DEGs were mainly enriched in PPAR, non-alcoholic fatty liver disease, oxidative phosphorylation and other signaling pathways. Among them, eight genes of ACSL4, CYP7A1, FABP4, FABP5, lipoprotein lipase, ME1, OLR1 and PLIN1 were enriched in PPAR signaling pathway, and 165 interaction nodes were formed with 47 DEGs-encoded proteins. Lipoprotein lipase interacted with 21 DEGs, and its up-regulated expression had improved lipid metabolism, insulin resistance and anti-inflammatory effects. Four drugs (gemfibrozil, bezafibrate, omega-3 carboxylic acid and glycyrrhizic acid) were screened by L1000 and DrugBank to activate lipoprotein lipase. Presently, these four drugs are clinically used to treat hypertriglyceridemia or to improve inflammation. In this regard, we speculated that the pharmacological effects of these four drugs had improved NASH by activating lipoprotein lipase to promote liver lipid metabolism and alleviate inflammation. Conclusion: PPAR signaling pathway is closely associated to the occurrence and development of NASH, and thereby lipoprotein lipase agonist is a new attempt to treat NASH.

Over-expression of MEOX2 promotes apoptosis through inhibiting the PI3K/Akt pathway in laryngeal cancer cells.

The early-stage diagnosis and treatment for the recurrence of larynx carcinoma needs further investigation. Mesenchyme homeobox 2 (MEOX2) was speculated as a novel suppressor gene in larynx carcinoma in our study, the molecular mechanism was studied. Real-time quantitative PCR (RT-qPCR) and Western blot were used to detect mRNA and protein levels of MEOX2 in laryngeal cancer tissues and cells (Hep-2, TU212, AMC-NH-8 and TU686 cells), and also apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase (Akt) related factors in TU212 cells transfected with MEOX2. Cell counting kit-8 (CCK8) assay and Annexin-Ⅴ/PI staining assay were conducted to determine cell viability and apoptosis rates respectively.46 patients with larynx carcinoma were involved in this study. The expression of MEOX2 was lower in larynx carcinoma tissues than normal tissues, correlated with clinical stages, differentiated degrees, and survival times. The expression of MEOX2 was the lowest among those laryngeal cancer cells, and was chosen to be transfected with MEOX2 in the following study. Over-expression of MEOX2 inhibited cell viability and promoted apoptosis of TU212 cells, via increasing the expression levels of Caspase-3, and decreasing levels of C-Myc, XIAP, PI3K p110α, PI3K p110ß, PI3K class III and p-Akt. In summary, the expression levels of MEOX2 were inhibited in larynx carcinoma than normal tissues, correlated with the progression of the cancer. Over-expression of MEOX2 in laryngeal cancer cells inhibited cell viability and promoted apoptosis, via regulating apoptosis and PI3K/Akt pathway related factors. It would provide evidence for MEOX2 to be used as a therapeutical gene in larynx carcinoma.

[Clinical study of maternal and infant outcomes in patients with lupus nephritis complicated with pregnancy].

Objective: To investigate the outcomes and associated factors for adverse pregnancy outcomes (APO) in pregnant patients with lupus nephritis (LN). Methods: The clinical data of 139 LN pregnant patients from from 2009 to 2017 in the First Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively. Results: Totally, 105 LN were diagnosed before pregnancy and 34 were newly diagnosed during pregnancy. One or more APO occurred in 71.2% of patients with LN and 40 (28.8%) were without any APO. Thirty-six (25.9%) of pregnancies resulted in fetal loss. A total of 54 pregnancies were preterm birth with 20 at gestational age <34 weeks, 13 were intrauterine growth retardation (IUGR), 3 were fetal distress, and 8 were neonatal lupus, pregnancy induced hypertension occurred in 18 cases, of which, 2 cases were gestational hypertension and 16 were preeclampsia. There was no eclampsia occurred.In multivariate analysis, predictors of APO included active lupus during pregnancy (OR=8.9, 95%CI: 3.7-21.7, P<0.001), rash (OR=7.3, 95%CI: 2.2-24.5, P=0.001), cylindruria (OR=5.3, 95%CI: 1.6-17.0, P=0.005) and antiphospholipid syndrome (OR=11.4, 95%CI: 1.5-88.3, P=0.02) were risk factors for pregnancy loss. Variables that were independently predictive of preterm birth included anticardiolipin antibody positive (OR=8.8, 95%CI: 1.5-51.5, P=0.02) and active lupus during pregnancy (OR=7.9, 95%CI: 2.3-24.5, P=0.001). Conclusions: Pregnancies in LN are still at high risk of APO in terms of pregnancy loss and preterm birth. Stable disease can help to reduce the risk of APO.

Survival analysis of the CEAwatch multicentre clustered randomized trial.

BACKGROUND: The CEAwatch randomized trial showed that follow-up with intensive carcinoembryonic antigen (CEA) monitoring (CEAwatch protocol) was better than care as usual (CAU) for early postoperative detection of colorectal cancer recurrence. The aim of this study was to calculate overall survival (OS) and disease-specific survival (DSS). METHODS: For all patients with recurrence, OS and DSS were compared between patients detected by the CEAwatch protocol versus CAU, and by the method of detection of recurrence, using Cox regression models. RESULTS: Some 238 patients with recurrence were analysed (7·5 per cent); a total of 108 recurrences were detected by CEA blood test, 64 (55·2 per cent) within the CEAwatch protocol and 44 (41·9 per cent) in the CAU group (P = 0·007). Only 16 recurrences (13·8 per cent) were detected by patient self-report in the CEAwatch group, compared with 33 (31·4 per cent) in the CAU group. There was no significant improvement in either OS or DSS with the CEAwatch protocol compared with CAU: hazard ratio 0·73 (95 per cent 0·46 to 1·17) and 0·78 (0·48 to 1·28) respectively. There were no differences in survival when recurrence was detected by CT versus CEA measurement, but both of these methods yielded better survival outcomes than detection by patient self-report. CONCLUSION: There was no direct survival benefit in favour of the intensive programme, but the CEAwatch protocol led to a higher proportion of recurrences being detected by CEA-based blood test and reduced the number detected by patient self-report. This is important because detection of recurrence by blood test was associated with significantly better survival than patient self-report, indirectly supporting use of the CEAwatch protocol.

[Pregnancy outcome of planning pregnancies in patients with SLE].

Objectives: To investigate the pregnancy outcomes in systemic lupus erythematosus (SLE) patients with planning pregnancy.And to evaluate the value of fetal umbilical artery Doppler. Methods: A total of 130 SLE patients with planning pregnancy were prospectively recruited from January 2013 to January 2017 at the First Affiliated Hospital of Sun Yat-sen University. Results: Thirty eight (29.2%) patients had active lupus, 30 with mild activity, 5 with moderate activity and 3 with severe activity.Active disease in the first, second and third trimesters occurred in 6, 11 and 21 cases respectively.Lupus nephritis (76.3%) and hematological system involvement (39.5%) were the most common manifestation.Seven cases had pre-eclampsia during pregnancy.One or more adverse outcomes occurred in 40 patients, including 28 with premature, 12 with pregnancy loss, 9 with intrauterine growth restriction, and 8 with fetal distress.All of the pulsatility index, resistance index and S/D value of patients with adverse outcomes were higher than that of patients without adverse outcomes (P<0.05). Conclusions: In SLE patients with planning pregnancy, disease flares were infrequent, and outcomes were favorable. Fetal umbilical artery Doppler can be used as a noninvasive monitoring method for SLE patients at late pregnancy.

[Role of CD36 in nonalcoholic fatty liver disease].

Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic simple fatty liver, nonalcoholic steatohepatitis, liver cirrhosis, and liver cancer and is the most common liver disease in the world. The complex pathogenesis of NAFLD is a major concern among researchers. CD36 is a transmembrane glycoprotein that takes up fatty acid and binds to oxidized low-density lipoprotein in the liver, and therefore, it is involved in the development and progression of NAFLD. With reference to the latest research findings, this article reviews the association between CD36 and NAFLD and the role of CD36.

[Analysis of pulmonary valve function in patients with tetralogy of Fallot after radical surgery].

Objective: To analyze the pulmonary valve function in patients with tetralogy of Fallot after radical surgery. Methods: Clinical data of 263 patients (119 male, mean age (33.2±11.5) years old) with tetralogy of Fallot underwent radical surgery in our hospital from January 2010 to June 2016 were retrospectively analyzed. According to age, patients were divided into 14-17 years old group (14 cases), 18-29 years old group (100 cases), 30-39 years old group (61 cases) and above 40 years old group (87 cases). The patients were divided into pulmonary regurgitation group (87 cases) and control group (176 cases) according to weather they have moderate or severe pulmonary regurgitation. Echocardiographic data were compared among groups. Results: A total of 83 patients received re-operation. The median age of the primary radical operation was 9 (5, 13) years, and the median time from the primary radical operation to echocardiographic follow-up was 5 (1, 13) years. Among the 263 enrolled patients, prevalence of pulmonary regurgitation was 36.1% (95/263), and pulmonary stenosis was evidenced in 28 patients (10.6%). The ratio of moderate to severe tricuspid regurgitation was 14.3% (2/14), 27.0% (27/100), 32.8% (20/61) and 37.9% (33/87) in 14-17 years old group, 18-29 years old group, 30-39 years old group and above 40 years old group, respectively (P=0.029), while prevalence of moderate and severe pulmonary regurgitation, moderate and severe pulmonary valve stenosis, pulmonary valve transvalvular pressure >40 mmHg (1 mmHg=0.133 kPa), right atrial and right ventricular enlargement ratio were similar among groups (all P>0.05). The ratio of moderate and severe tricuspid regurgitation and right ventricular enlargement in the pulmonary regurgitation group was significantly higher than in the control group (40.2% (35/87) vs. 27.3% (48/176) and 96.6% (84/87) vs. 87.5% (154/176), all P<0.05), while left ventricular ejection fraction, right atrial enlargement, and right ventricular wall thickness were similar between the two groups (all P>0.05). Conclusion: Pulmonary regurgitation is a common clinical feature among survivors of tetralogy of Fallot patients after radical surgery, and moderate to severe pulmonary regurgitation increases the risk of tricuspid regurgitation and enlargement of the right ventricle.

[Clinical features and adverse pregnancy outcomes of new onset systemic lupus erythematosus during pregnancy].

Objective: To investigate the clinical characteristics and adverse pregnancy outcomes in pregnant women with new onset systemic lupus erythematosus (SLE) during pregnancy. Methods: The clinical data of 263 pregnancies with SLE in the First Affiliated Hospital of Zhongshan University from 2001 to 2015 were collected and analyzed retrospectively. Results: Of all the 263 pregnancies, 188 were diagnosed before pregnancy and 75 were newly diagnosed during pregnancy. Among the 75 new onset SLE, 27, 31, 14 and 3 cases were diagnosed during first trimester, second trimester, third trimester and puerperium, respectively. Active lupus was noted in 81.3% of the patients with new onset SLE. The main clinical manifestations of new onset SLE were lupus nephritis (57.3%) and thrombocytopenia (38.7%). SLEPDAI scores as well as the prevalence of lupus nephritis, and thrombocytopenia in patients with new onset SLE was higher than those in the previously diagnosed ones (P<0.05). Among the 75 new onset SLE pregnancies, adverse pregnancy outcomesoccurred in 53 patients, including 34 with pregnancy loss, 15with premature, 8with intrauterine growth restriction, 5with fetal distress and5 with neonatal lupus. Compared with patients withnon-newonset SLE, patients with newonset SLEhad a higher prevalence of adverse pregnancy outcomes (56.4% vs 70.7%, P<0.05), and pregnancy loss (21.8% vs 45.3%, P<0.01) but less live birth (78.2% vs 54.7%, P<0.05). Conclusion: Most of the patients with new onset SLE occurred during the first and second trimester. The most common clinical features of new onset SLE were lupus nephritis and thrombocytopenia. Patients with new onset SLE were more prone to active lupus, lupus nephritis and thrombocytopenia, as well as more adverse pregnancy outcomes and pregnancy loss.

SPG35 contributes to the second common subtype of AR-HSP in China: frequency analysis and functional characterization of FA2H gene mutations.

Hereditary spastic paraplegias (HSPs) encompass a clinically and genetically heterogeneous group of neurodegenerative disorders. Recently, mutations in fatty acid 2-hydroxylase gene (FA2H) have been identified responsible for HSPs type 35 (SPG35). This study aims to define the contribution of FA2H to Chinese autosomal recessive HSP (AR-HSP) patients and provide insights into the enzymatic functions of the novel mutations. Direct sequencing of FA2H was conducted in 31 AR-HSP families and 55 sporadic cases without SPG11, SPG15, SPG5 and SPG7 gene mutations. Enzymatic activity of the mutated proteins was further examined. Three novel mutations were found in two Chinese families, including two compound heterozygous mutations (c.388C>T/p.L130F and c.506+6C>G) and one homozygous mutation (c.230T>G/p.L77R). The c.506+6C>G splice-site mutation led to the deletion of exon 3. Measurement of enzymatic functions revealed a significant reduction in the enzymatic activity of FA2H associated with p.L130F and p.L77R. Overall, our data widens the spectrum of the mutations on FA2H, and functional analyses indicate that these mutations severely impair the enzymatic activity of FA2H. Furthermore, frequency analysis shows that SPG35 is the second most common subtype of AR-HSP in China.

Detection of serum anti-melanocyte antibodies and identification of related antigens in patients with vitiligo.

We detected autoantibodies against melanocytes in serum samples obtained from 50 patients, including 4 with HBV, with vitiligo and identified the associated membrane antigens. Heat shock protein 70 (HSP70) and anti-tyrosinase-related protein 1 (TRP-1) antibody levels were analyzed. The associated antigens in normal human melanocyte were identified by immunofluorescence. Autoantibodies against melanocyte membrane and cytoplasmic proteins were detected by western blot. Membrane antigens with higher frequencies were identified by protein mass spectrometry. The HSP70 and anti-TRP-1 antibody levels (N = 70; 10 with HBV) were detected by ELISA. The specific antigens were detected in melanocyte cytoplasm and membrane (40/50; 80% incidence; western blot). The autoantibodies reacted with several membrane antigens with approximate molecular weights (Mr) of 86,000, 75,000, 60,000, 52,000, and 44,000 (strip positive rates: 36, 58, 22, 2, and 2%, respectively). Thirty percent of the patients showed the presence of cytoplasmic antigens (Mr: 110,000, 90,000, 75,000, 50,000, and 400,000; strip positive rates: 12, 4, 12, 10, and 2%, respectively). Fifteen and 5% of the healthy subjects showed positive expression of membrane and cytoplasmic antigens, respectively. Protein mass spectrometry predicted membrane proteins with Mr of 86,000 and 75,000 and 60,000 to be Lamin A /C and Vimentin X1, respective. High titers of anti-TRP-1 antibody were detected and showed positive correlation with HSP70 (r = 0. 927, P < 0. 01). This study identified a novel membrane antigen associated with vitiligo, which might assist future investigations into autoimmune pathogenesis of vitiligo and formation of autoantibodies. HBV infection was correlated to vitiligo.

Interleukin-10 polymorphisms and nasopharyngeal carcinoma risk: a meta-analysis.

It has been reported that interleukin-10 (IL-10) promoter genes (1082 A/G, 819 T/C, 592 A/C) are associated with nasopharyngeal carcinoma (NPC). However, the results remain controversial and ambiguous. To resolve inconsistencies in published data, we performed a meta-analysis to ascertain the association between IL-10 polymorphisms and NPC risk. Two case-control studies and two cohort studies were quantitatively analyzed to evaluate IL-10 promoter gene polymorphisms and NPC risk. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for each genetic model and allelic comparison. A random-effect model or a fixed-effect model was used to calculate the overall combined risk estimates. Overall, the variant genotypes (AA and AG) of the IL-10-1082 A/G polymorphism were associated with elevated risk of NPC compared with the GG homozygote (AG vs GG: OR = 1.77; 95%CI = 1.39-2.26; AG + GG vs AA: OR = 1.78; 95%CI = 1.42-2.22); no significant associations were observed in allelic contrast and the recessive model. Strong positive association was seen in the cohort studies but not in the case-control studies. No statistically significant association was detected between IL-10-819 T/C and IL-10-592 A/C polymorphisms and NPC. Additionally, publication bias was not found. Based on the current evidence, this meta-analysis suggests that IL-1082 A/G polymorphism may increase the risk of NPC, but IL-10-819 T/C and IL-10-592 A/C polymorphisms do not. Further multicenter studies that are better controlled are required to confirm these findings.

To screen or not to screen for breast cancer? How do modelling studies answer the question?

Breast cancer screening is a topic of hot debate, and currently no general consensus has been reached on starting and ending ages and screening intervals, in part because of a lack of precise estimations of the benefit-harm ratio. Simulation models are often applied to account for the expected benefits and harms of regular screening; however, the degree to which the model outcomes are reliable is not clear. In a recent systematic review, we therefore aimed to assess the quality of published simulation models for breast cancer screening of the general population. The models were scored according to a framework for qualitative assessment. We distinguished seven original models that utilized a common model type, modelling approach, and input parameters. The models predicted the benefit of regular screening in terms of mortality reduction; and overall, their estimates compared well to estimates of mortality reduction from randomized controlled trials. However, the models did not report on the expected harms associated with regular screening. We found that current simulation models for population breast cancer screening are prone to many pitfalls; their outcomes bear a high overall risk of bias, mainly because of a lack of systematic evaluation of evidence to calibrate the input parameters and a lack of external validation. Our recommendations concerning future modelling are therefore to use systematically evaluated data for the calibration of input parameters, to perform external validation of model outcomes, and to account for both the expected benefits and the expected harms so as to provide a clear balance and cost-effectiveness estimation and to adequately inform decision-makers.