Inhibitor of apoptosis proteins (IAP) inhibitor APG-1387 monotherapy or in combination with programmed cell death 1 (PD-1) inhibitor toripalimab in patients with advanced solid tumors: results from two phase I trials.

BACKGROUND: APG-1387 is a novel second mitochondrial-derived activator of caspases mimetic, small-molecule inhibitor targeting inhibitor of apoptosis proteins. We report results from two phase I trials evaluating the tolerability, safety, and antitumor activity of APG-1387 monotherapy and APG-1387 plus toripalimab [a programmed cell death 1 (PD-1) inhibitor] for advanced solid tumors. PATIENTS AND METHODS: Participants aged ≥18 years who had histologically confirmed advanced solid tumors with no appropriate standard of care (or refractory to standard care) were eligible. Patients received escalating intravenous doses of APG-1387 alone or combined with fixed-dose toripalimab (240 mg every 3 weeks) in a '3 + 3' design. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) in the monotherapy trial, and recommended phase II dose (RP2D) in the combination therapy trial. Secondary endpoints included the pharmacokinetic and pharmacodynamic profiles and preliminary efficacy in both trials. RESULTS: In the monotherapy trial, 28 subjects were enrolled and received ≥1 treatment cycle. No DLT was reported among the 28 subjects, and the MTD was not reached. One participant (3.6%) had a grade ≥3 treatment-related adverse event (TRAE) of alanine aminotransferase elevation. In efficacy analysis of 23 participants, none achieved an objective response, and the disease control rate was 21.7%. In the combination trial, 22 subjects were enrolled and included in all analyses. There was one DLT of grade 3 lipase elevation. The MTD was not reached. Four grade ≥3 TRAEs occurred in three participants (13.6%), with the most common being lipase elevation (n = 2). The RP2D was 45 mg weekly. The objective response rate was 13.6%, with complete response achieved in one subject, and the disease control rate was 54.5%. CONCLUSIONS: APG-1387 45 mg weekly plus toripalimab was well tolerated and is recommended for further study, with preliminary clinical activity observed in study participants with advanced solid tumors.

Retraction Note: MiR-1294 acts as a tumor suppressor in clear cell renal cell carcinoma through targeting HOXA6.

The article "MiR-1294 acts as a tumor suppressor in clear cell renal cell carcinoma through targeting HOXA6", by W. Pan, L.-J. Pang, H.-L. Cai, Y. Wu, W. Zhang, J.-C. Fang, published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 3719-3725-DOI: 10.26355/eurrev_201905_17797-PMID: 31114997 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer regarding a possible manipulation in Figures 2 and 3, the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The authors have been informed about the journal's investigation but remained unresponsive. The journal investigation revealed duplications in panels miR-1294 mimic - Caki01 and Caki01 of Figure 2D and in the Western blots of Figure 3 with previously published articles. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17797.

Interplay of metabolic dysfunction-associated fatty liver disease and papillary thyroid carcinoma: insights from a Chinese cohort.

PURPOSE: Thyroid cancer is one of a set of extrahepatic cancers that closely linked to metabolic dysfunction-associated fatty liver disease (MAFLD). However, the connection between MAFLD and the characteristics of papillary thyroid cancer (PTC) remains unexplored. METHODS: Between Jan 2020 and Oct 2022, surgical cases of PTC patients were examined at the first Affiliated Hospital of Wenzhou Medical University. Clinical data extracted from the electronic medical system underwent a rigorous comparison between two groups, classified based on MAFLD criteria, using logistic regression analysis. RESULTS: In this study of 4,410 PTC patients, 18.3% had MAFLD. MAFLD emerged as a distinct risk factor for lymph node metastasis (OR = 1.230, 95% CI 1.018-1.487) in this cohort, especially in females (OR = 1.321, 95% CI 1.026-1.702) and those with BMI ≥ 23 kg/m2 (OR = 1.232, 95% CI 1.004-1.511). The presence of MAFLD was found to significantly elevate the risk of BRAF V600E mutation in both subgroups characterized by FIB-4 score ≥ 1.3 (OR = 1.968, 95% CI 1.107-3.496) and BMI < 23 kg/m2 (OR = 2.584, 95% CI 1.012-6.601). Moreover, among the subset of individuals without non-alcoholic fatty liver disease (NAFLD), it was noted that MAFLD considerably increased the likelihood of tumor multifocality (OR = 1.697, 95% CI 1.111-2.592). Nevertheless, MAFLD did not exhibit any correlation with increased tumor size, extra-thyroidal extension (ETE), or later TNM stage in PTC. CONCLUSION: In this cross-sectional study, we discovered a significant association between MAFLD and increased occurrences of lymph node metastasis. Furthermore, MAFLD was linked to a higher chance of BRAF V600E mutation and the presence of multiple tumors in certain subgroups.

[Comparison of ultrathin bronchoscopy with conventional bronchoscopy for the diagnostic value of peripheral pulmonary lesions].

Objective: To assess and compare the diagnostic efficacy of next-generation ultrathin bronchoscopy (UTB) and conventional bronchoscopy (CB), both combined with radial endobronchial ultrasound (r-EBUS), in the evaluation of peripheral pulmonary lesions (PPL). Methods: A cohort of 39 patients with PPL who underwent multimodal bronchoscopy at Dushu Lake Hospital, Soochow University, from June 1, 2021 to May 31, 2023 was consecutively enrolled. A single bronchoscopist performed multimodal bronchoscopies using CB (external diameter 4.9 mm or 5.9 mm, working channel diameter 2 or 3 mm, CB group) for transbronchial biopsy under r-EBUS guidance (rEBUS-TBLB), followed by UTB (external diameter 3 mm, working channel diameter 1.7 mm, UTB group) for transbronchial biopsy under r-EBUS guidance. Pathological findings and a 6-month clinical follow-up were used as the gold standard to compare the diagnostic yield of biopsy specimens, ultrasound characteristics, and localization rates of the two bronchoscope types. The aim was to evaluate the clinical application value of UTB combined with r-EBUS. Binary variables were analysed using the McNemar test for paired data. Continuous variables or ranked data were analysed using the Wilcoxon signed-rank test for paired data. Results: The diagnostic yields for UTB and CB groups were 66.67% (26/39) and 30.77% (12/39), respectively, with the UTB group significantly surpassing the CB group (χ2=10.56, P=0.001, 1-ß=0.968). r-EBUS with CB exhibited no visible lesion in 13 cases, adjacent to the lesion in 19 cases, and within the lesion in 7 cases.Substitution of UTB resulted in r-EBUS images changing from no visible lesion to adjacent to the lesion in 7 cases, from no visible lesion to within the lesion in 3 cases, and from adjacent to the lesion to within the lesion in 12 cases. The positioning of the r-EBUS probe in relation to the lesions improved significantly with UTB usage (Z=-4.46, P<0.001). Localization rates (number of patients with "within" or "adjacent to" the image/total number of patients) for UTB and CB were 92.30% (36/39) and 66.67% (26/39), respectively (χ2=8.10, P=0.002). UTB improved r-EBUS probe localization rates. The diagnostic yields of UTB were higher than CB for solid lesions, lesions>30 mm in diameter, non-upper lobar location, benign or malignant lesions and lesions with or without a bronchus sign. Conclusion: The UTB group demonstrated a significantly higher diagnostic yield than the CB group, providing superior r-EBUS probe images, and a significant diagnostic advantage for PPL.

Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522.

BACKGROUND: KEYNOTE-522 demonstrated statistically significant improvements in pathological complete response (pCR) with neoadjuvant pembrolizumab plus chemotherapy and event-free survival (EFS) with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in patients with high-risk, early-stage triple-negative breast cancer (TNBC). Prior studies have shown the prognostic value of the residual cancer burden (RCB) index to quantify the extent of residual disease after neoadjuvant chemotherapy. In this preplanned exploratory analysis, we assessed RCB distribution and EFS within RCB categories by treatment group. PATIENTS AND METHODS: A total of 1174 patients with stage T1c/N1-2 or T2-4/N0-2 TNBC were randomized 2 : 1 to pembrolizumab 200 mg or placebo every 3 weeks given with four cycles of paclitaxel + carboplatin, followed by four cycles of doxorubicin or epirubicin + cyclophosphamide. After surgery, patients received pembrolizumab or placebo for nine cycles or until recurrence or unacceptable toxicity. Primary endpoints are pCR and EFS. RCB is a prespecified exploratory endpoint. The association between EFS and RCB was assessed using a Cox regression model. RESULTS: Pembrolizumab shifted patients into lower RCB categories across the entire spectrum compared with placebo. There were more patients in the pembrolizumab group with RCB-0 (pCR), and fewer patients in the pembrolizumab group with RCB-1, RCB-2, and RCB-3. The corresponding hazard ratios (95% confidence intervals) for EFS were 0.70 (0.38-1.31), 0.92 (0.39-2.20), 0.52 (0.32-0.82), and 1.24 (0.69-2.23). The most common first EFS events were distant recurrences, with fewer in the pembrolizumab group across all RCB categories. Among patients with RCB-0/1, more than half [21/38 (55.3%)] of all events were central nervous system recurrences, with 13/22 (59.1%) in the pembrolizumab group and 8/16 (50.0%) in the placebo group. CONCLUSIONS: Addition of pembrolizumab to chemotherapy resulted in fewer EFS events in the RCB-0, RCB-1, and RCB-2 categories, with the greatest benefit in RCB-2. These findings demonstrate that pembrolizumab not only increased pCR rates, but also improved EFS among most patients who do not have a pCR.

Sex-Specific Associations of Dietary Iron Intake with Brain Iron Deposition on Imaging and Incident Dementia: A Prospective Cohort Study.

OBJECTIVES: The study aimed to evaluate the association of dietary iron intake with incident dementia and brain iron deposition. DESIGN/SETTING/PARTICIPANTS: We included dementia-free participants from the UK Biobank who completed at least one 24-hour dietary recall at study baseline (2009-2012) and were followed up to 2021. Incident dementia was determined through linkage to medical records and death registries. Brain MRI was conducted in a subgroup of participants since 2014, with T2* measurements being used as indicators of brain iron deposition. MEASUREMENTS: Cox proportional hazard models were used to assess the associations of high (top quintile) and low (bottom quintile) versus medium (quintile 2 to 4) level of dietary iron intake with incident dementia, respectively. Linear regression was applied to assess the relations between dietary iron intake and brain T2* measurements. RESULTS: During follow-up (mean = 9.5 years), a total of 1,454 participants (650 women and 804 men) developed dementia among 191,694 participants (55.0% female; mean age, 56.2 years). When adjusted for sociodemographic, lifestyle, and other dietary factors, participants with low dietary iron intake (< 10.05 mg/day) had a significantly higher dementia risk (hazard ratio [HR], 1.50, 95% confidence interval [CI], 1.19-1.89), while the relation for high intake (> 16.92 mg/day) was non-significant (HR, 1.16, 95% CI, 0.92-1.46). A significant gender difference (P-interaction < 0.001) was observed, with a U-shaped association in male participants (HR for low vs. medium, 1.56, 95% CI, 1.14-2.13; HR for high vs. medium, 1.39, 95% CI, 1.03 - 1.88; P-nonlinearity < 0.001) and no significant association in females, regardless of their menopause status. In general, dietary iron intake was not related to T2* measurements of iron deposition in most brain regions. CONCLUSION: Our findings suggested a U-shape relationship between dietary iron intake and risk of dementia among males, but not females.

[Phacoemulsification combined with goniosynechialysis under a gonioscope in the treatment of angle-closure glaucoma: the effect of reopening the synechial anterior chamber angle].

A total of 170 consecutive patients (181 eyes) who were diagnosed with primary angle-closure glaucoma (PACG) and underwent phacoemulsification and intraocular lens implantation (PEI) combined with goniosynechialysis (GSL) with an instrument under a gonioscope in the Eye Hospital, Wenzhou Medical University from January 1, 2017 to December 31, 2019 were observed. Anterior chamber angle synechiae of 0 (0, 2) clock hour were released after PEI, while after combined goniosynechialysis, synechiae of 6 (3, 8) clock hours were further released. No matter in chronic PACG and acute PACG with cornea edema, the extent of anterior chamber angle synechiae was different before surgery and after PEI, and so was it in post-PEI and PEI-GSL prospectively (all P<0.01). Phacoemulsification alone can reopen the synechial anterior chamber angle in both chronic PACG and acute PACG in part, but not sufficiently. Combined goniosynechialysis under a gonioscope with an instrument is essential and effective.

[Preliminary evaluation on the efficacy of emergency transcatheter aortic valve replacement: a multicenter study].

Objectives: To explore the efficacy and safety of emergency transcatheter aortic valve replacement (TAVR). Methods: Data of patients who underwent emergency TAVR in eight centers, namely Fuwai Hospital, Wuhan Asia Heart Hospital, Xijing Hospital, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Guangdong Provincial People's Hospital, Zhongshan Hospital Affiliated to Fudan University, the First Affiliated Hospital of Zhengzhou University, the Second Xiangya Hospital of Central South University, between May 2017 and December 2020 were retrospectively analyzed. The use of mechanical circulatory support system (MCS) and the results of laboratory tests (N-terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography (mean aortic valve cross valve pressure difference and left ventricular ejection fraction) before and after operation were collected. The primary endpoint was all-cause death, and the secondary endpoints were stroke, major bleeding, major vascular complications, myocardial infarction, permanent pacemaker implantation, and acute renal injury. Device success was caculated, which refered to absence of procedural mortality and correct positioning of a single prosthetic heart valve into the proper anatomical location and intended performance of the prosthetic heart valve (mean aortic valve gradient<20 mmHg(1 mmHg=0.133 kPa) or peak velocity<3 m/s, with no moderate or severe prosthetic valve regurgitation). Kaplan-Meier survival curve was used to estimate the survival rate of patients during follow-up. Results: This study included 48 patients. The age was (72.5±8.1) years, and 34 patients were males (70.8%). Device success rate was 91.7% (44/48). The mean aortic valve transvalvular pressure was significantly decreased after operation ((12.3±6.4)mmHg vs. (60.2±23.8)mmHg, P<0.000 1). Left ventricular ejection fraction was significantly increased ((41.5±11.7)% vs. (31.0±11.3)%, P<0.000 1). NT-proBNP significantly decreased (3 492.0 (1 638.8, 7 165.5) ng/L vs. 12 418.5 (6 693.8, 35 000.0) ng/L, P<0.000 1). In-hospital all-cause mortality was 8.3% (4/48). During hospitalization, the rate of stroke was 2.1% (1/48), major bleeding was 6.3% (3/48), major vascular complications was 10.4% (5/48), myocardial infarction was 4.2% (2/48), permanent pacemaker implantation was 6.3% (3/48), and the rate of acute renal injury was 12.5% (6/48). MCS was used in 20 patients (41.7%). The median follow-up time was 196 days. During the follow-up, one patient died (due to systemic metastasis of pancreatic cancer), two cases suffered new myocardial infarction and one case received permanent pacemaker implantation. The survival rate of 30 days, 1 year and 2 years after the operation were 91.7% (44/48), 89.6% (43/48), 89.6% (43/48), respectively. Conclusion: Emergency TAVR may be a safe and effective treatment for patients with severe decompensated aortic valve stenosis.

[Follow-up study of fetal cardiac birth defects after prenatal diagnosis and graded counseling].

Objective: To explore accurate prenatal diagnosis, full-coverage graded counseling and follow-up for the fetus with cardiac birth defects (CBD). Methods: CBD fetus diagnosed prenatal by echocardiography from January 2018 to December 2020 in Guangdong Provincial People's Hospital were enrolled. Fetal CBD was graded (Ⅰ-Ⅵ) according to prognosis and possible operation time after birth, and the classification criteria and common diseases included were proposed. After the prenatal grading counseling, the outcome of the fetus was followed-up. The induced labor rate, live birth rate, prenatal and postnatal ultrasound diagnosis coincidence rate and other indicators were calculated. The disease composition ratio, prognosis of fetus with different grades and the outcome of integrated treatment were analyzed. Results: The detection rate of fetal CBD was up to 16.2% (1 971/12 188), 30 cases of which were excluded. A total of 1 941 cases were included in this study, including 196 cases (10.1%) of gradeⅠ, 433 cases (22.3%) of gradeⅡ, 615 cases (31.7%) of grade Ⅲ, 261 cases (13.4%) of grade Ⅳ, 388 cases (20.0%) of gradeⅤ, 48 cases (2.5%) of grade Ⅵ. Grade Ⅱ and gradeⅢ (the operation time was within 1 year after birth) accounted for 54.0% (1 048/1 941). The distribution of some diseases in different grades had obvious proportion advantage, which was representative. Among 1 747 CBD fetus, 736 cases (induced labor rate 42.1%) chose to terminate pregnancy due to CBD. Of the 1 010 live births, 975 cases (96.5%) had the same prenatal and postnatal diagnosis, 3 cases were missed diagnosis and 32 cases were misdiagnosed. The diagnostic accuracy of live births with severe and complex congenital heart disease was 383 out of 389 (98.5%). A total of 258 cases have received surgery or intervention. The age at the time of surgery or intervention was different among grades（χ²=47.3，P<0.001）. With the improvement of prognosis from gradeⅠ to Ⅴ, the live birth rate increased and the induced labor rate decreased accordingly; the difference between grades was significant（χ²=623.6，P<0.001）. Conclusions: Prenatal diagnosis and graded counseling is important in the integrated model. Fetal CBD grading could refine post-natal treatment strategies, guide delivery decisions and become an evaluation standard.

[Efficacy of fenestrated atrial septal defect occulders on pulmonary hypertension dogs].

Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO2) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO2 at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery. Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.

[In vitro and in vivo anti-periodontitis effects of combination treatment of photodynamic and antibiotic therapies].

Objective: To investigate the effects of combination treatment of photodynamic therapy (PDT) based on photosensitizer chlorin e6 (Ce6) and antibiotic agent tinidazole (TNZ) against periodontitis both in vitro and in vivo. Methods: The Sprague-Dewley (SD) rat periodontitis model was constructed using the method of orthodontic wire ligation. After successful modeling, SD rats were randomly divided into the following 6 groups (3 rats in each group): positive control (Ctrl+), Ce6, TNZ, a mixture of Ce6 and TNZ (Ce6/TNZ), Ce6 with laser irradiation (Ce6+L), a mixture of Ce6 and TNZ with laser irradiation (Ce6/TNZ+L). Methyl thiazolyl tetrazolium (MTT) assay was used to assess the cytotoxic activities of Ce6 (concentration range: 0-20 mg/L), TNZ (concentration range: 0-16.6 mg/L) and their mixture (Ce6/TNZ) in mouse fibroblast L929 cells. Fluorescence probe method was applied to measure the production of reactive oxygen species in the dental plaque biofilms after various treatments with and without 5-minute laser irradiation at 635 nm at a power density of 0.5 W/cm2 (Ce6+L and Ce6/TNZ+L groups), thus to evaluate the PDT performances. Cell counting kit-8 (CCK-8) and live/dead staining were used to assess the antibacterial activity in each of the groups and the combination index (CI) of PDT combined with TNZ was calculated subsequently. Flow cytometry was utilized to detect the apoptosis-inducing effects of these treatments in macrophage RAW264.7 cells after processing with the apoptosis detection kit. The inhibitory effects of various treatments on the absorption of alveolar bone of SD rats were further evaluated in the periodontitis rats by using the micro-CT. Results: The survival rates of L929 cells in the preset concentration range were all above 90% in Ce6, TNZ and Ce6/TNZ groups. Upon laser irradiation, the plaque biofilms in Ce6 and Ce6/TNZ groups showed significant green fluorescence, indicating that large amounts of reactive oxygen species were triggered and generated significantly in the dental plaque biofilms. However, the survival rates of dental plaque microorganisms in 5 Ce6/TNZ concentrations were (85.4±5.5)%, (76.0±8.9)%, (61.7±0.6)%, (56.3±2.6)% and (43.5±0.6)% respectively, which were significantly lower than that in Ce6 only and TNZ only groups (P<0.01). The CI levle of each drug concentration group was less than 1.0, which showed a significant synergistic antibacterial efficiency. Stronger apoptotic activities were observed in Ce6+L and Ce6/TNZ+L groups compared with those in Ce6 only and Ce6/TNZ only groups (P<0.01). In periodontitis rats, Ce6/TNZ combined laser irradiation could effectively inhibit the absorption of alveolar bone. The alveolar bone volume and the ratio of bone volume and tissue volume were (1.49±0.07) mm3 and (47.08±0.71)%, respectively. The distances between cementoenamel junction to alveolar bone crest on buccal and palatal sites decreased to (2.13±0.07) mm and (1.94±0.10) mm respectively, showing a high inhibition efficiency. Conclusions: Ce6-mediated PDT combined with TNZ possessed notable synergistic effects against periodontitis, reflecting in the efficient antibacterial effect, the apoptosis-inducing action on macrophages, and the inhibitory efficacy on the alveolar bone absorption in vivo.

[Study on the prognostic value of preoperative anti hepatitis B virus therapy in patients with hepatocellular carcinoma complicated with microvascular tumor thrombus and establishment of survival prediction model].

Objective: To explored the effect of preoperative antiviral therapy on the prognosis of microvascular tumor thrombi patients, and to established a prognostic prediction model for these patients after radical resection of liver cancer. Methods: The clinicopathological and survival data of hepatocellular carcinoma patients with microvascular tumor thrombus who underwent radical resection in the Third Affiliated Hospital of Sun Yat-sen University from January 1, 2013 to December 31, 2015 were retrospectively collected. Kaplan-Meier method was used to calculate the survival curve, and log-rank test was used to compare the prognosis of patients with and without antiviral treatment before operation. Univariate and multivariate Cox proportional hazard regression model was used to screen predictive factors. R software was used to make predictive nomogram, and discrimination and calibration degree were used to evaluate the prediction model. Results: Among all 153 patients, 22 were female and 131 were male, aged (51.3±11.7) years. The preoperative antiviral therapy significantly improved overall survival and recurrence-free survival (χ2=41.423, 54.389; both P<0.001). According to the results of multivariate and regression analysis, preoperative antiviral therapy (HR=0.301,95%CI:0.171-0.532,P<0.001), alpha fetoprotein (HR=1.226,95%CI:1.157-1.776,P=0.032) and tumor size (HR=1.008,95%CI:1.001-1.016,P=0.02) were important prognostic factors for overall survival. The area under curve value of 3-year survival prediction model was 0.749(95%CI: 0.712-0.782), and that of 5-year survival prediction model was 0.755(95%CI: 0.724-0.793), with good calibration. Conclusions: Preoperative anti hepatitis B virus(HBV) therapy can significantly improve the prognosis of patients with hepatocellular carcinoma complicated with microvascular tumor thrombus, we develope the prediction models of 3-year and 5-year survival rate that can improve the reference for clinical work and benefit patients.

MiR-320c prevents the malignant development of cervical cancer by regulating GABRP level.

OBJECTIVE: This study aims to explore the role of microRNA-320c (miR-320c) in regulating biological behaviors of cervical cancer and the potential mechanism, thus providing experimental references for developing therapeutic target of cervical cancer. PATIENTS AND METHODS: Differential expressions of miR-320c in cervical cancer samples and normal cervical tissues were determined. Potential association between miR-320c level and clinical characteristics of cervical cancer patients was analyzed. After overexpression of miR-320c, migratory potential changes in HeLa, and C33-A cells were examined. At last, target gene binding to miR-320c was predicted online and its involvement in the malignant development of cervical cancer was finally explored. RESULTS: It was found that miR-320c was lowly expressed in cervical cancer tissues. Compared with cervical cancer patients with high expression of miR-320c, those with low expression had higher rates of lymphatic metastasis and distant metastasis. Besides, the overexpression of miR-320c markedly inhibited migratory potential in HeLa and C33-A cells. GABRP was verified to be the target gene binding to miR-320c. Notably, GABRP was able to reverse the role of miR-320c in regulating migratory potential in cervical cancer. CONCLUSIONS: MiR-320c is capable of inhibiting migratory potential in cervical cancer by targeting GABRP, which may be utilized as a therapeutic target of cervical cancer.

[Analysis of treatment modalities and prognosis of patients with gallbladder cancer in China from 2010 to 2017].

Objective: To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China. Methods: This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed. Results: Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn't be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%. Conclusions: More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

Improved survival and survival without bronchopulmonary dysplasia in very low birth weight infants after active perinatal care.

BACKGROUND: Perinatal and neonatal care for very low birth weight (VLBW) infants have changed significantly during the past two decades. However, it is unclear how these changes have affected neonatal mortality and morbidity in developing countries. OBJECTIVES: The aim of this study was to investigate the impact of the advanced neonatal care on short-term outcomes of VLBW infants. METHODS: A retrospective study was performed to compare the mortality and morbidity of VLBW infants between period I (2007-2011) and period II (2012-2016) in our unit. RESULTS: A total of 188 infants in period I and 214 infants in period II were evaluated. The overall in-hospital mortality for VLBW infants dropped from 26.1% in period I to 13.1% in period II. The incidence of birth asphyxia decreased significantly during period II (10.1% [period I] vs 3.7% [period II]). The rate of nasal continuous positive airway pressure (NCPAP) use (69.8% vs 87.1%) and the duration of NCPAP therapy (median: 3 days [period I] vs 5 days [period II]) increased significantly, while the proportion of infants treated with mechanical ventilation and the duration of mechanical ventilation significantly decreased. There was a significant increase in the proportion of survivors without major neonatal morbidity, mainly due to a significant increase in the incidence of survival without bronchopulmonary dysplasia (BPD) (72.7% vs 82.8%). In contrast, the incidence of late-onset sepsis increased significantly during period II (7.9% vs 19.4%). CONCLUSIONS: Active perinatal care is associated with improvements in survival and survival free of BPD for VLBW infants. However, late-onset sepsis is still a major concern.

Enhanced stability of quantum Hall skyrmions under radio-frequency radiations.

We present in this paper the results from a recent study on the stability of the quantum Hall skyrmions state at a Landau level filling factor (ν) close to ν = 1 in a narrow GaAs quantum well. Consistent with previous work, a resonant behavior is observed in the resistively detected NMR measurements. In the subsequent current-voltage (I-V) measurements to examine its breakdown behavior under radio frequency radiations, we observe that the critical current assumes the largest value right at the 75As nuclear resonant frequency. We discuss possible origin for this unexpectedly enhanced stability.

HOXA10 promotes the development of bladder cancer through regulating FOSL1.

OBJECTIVE: This study was aimed to investigate the expression characteristics of HOXA10 in bladder cancer (BCa), and to further study whether it can promote the development of BCa via regulating FOSL1. PATIENTS AND METHODS: The expression of HOXA10 was examined by quantitative Real Time-PCR (qRT-PCR) in 37 pairs of tumor tissue and paracancerous specimens of BCa patients; meanwhile, in BCa cell lines, the expression of HOXA10 was also verified using qRT-PCR. Subsequently, after HOXA10 knockdown model was constructed in BCa cell lines (EJ and J82) using lentivirus transfection, transwell, as well as wound healing assays, were performed to analyze the influence of the downregulation of HOXA10 on the biological function of BCa cells. Finally, Luciferase reporting assay and cell reverse experiment were applied to explore the specific interaction between HOXA10 and FOSL1. RESULTS: The results of qRT-PCR indicated that the expression level of HOXA10 in BCa tissue samples was remarkably higher than that in adjacent normal ones, with a statistically significant difference. At the same time, the overall survival rate of patients with high expression of HOXA10 was found to be lower than those with low expression. Meanwhile, compared with cells in sh-NC group, the metastasis ability of BCa cells in sh-HOXA10 group was remarkably weakened. In addition, it was found that the levels of FOSL1 and HOXA10 were negatively correlated in BCa tissues. The result of the Luciferase reporter gene assay revealed that HOXA10 could be targeted by FOSL1 through certain binding sites between them. In addition, HOXA10 was found to be capable of further regulating the malignant progression of BCa by modulating FOSL1. CONCLUSIONS: HOXA10 expression is remarkably elevated in BCa tissues and cell lines, which is closely relevant to the poor prognosis of BCa patients. In addition, HOXA10 may be able to accelerate BCa metastasis via modulating FOSL1 expression.

High sugar-sweetened beverage intake frequency is associated with smoking, irregular meal intake and higher serum uric acid in Taiwanese adolescents.

Types of sugar-sweetened beverages (SSB) can differ greatly between countries, with greater consumption of sweetened tea in Asia. This study aimed to understand changes in SSB consumption by adolescents in Taiwan over 18 years and their association with demographic characteristics and clinical outcome. This study used survey data from the 1993-1996 and 2010-2011 Nutrition and Health Surveys in Taiwan. Participants were high school students aged 13 to 18 years. Data were weighted and analysed using SUDAAN 11.0 and SAS 9.4. Participants were asked about intake frequencies of SSB and were grouped into four different SSB intake groups based on the combination of high or low frequency (including moderate frequency) of intake of sweetened tea and soda/sports/energy drinks. Results indicated over 99 % of teens reported having at least one SSB in the past week. Smoking status was significantly associated with SSB intake types with high tea intake (high tea and low soda (HL) group, OR 7·56, P < 0·001; high tea and high soda (HH) group, OR 9·96, P < 0·001). After adjustment for potential confounders, adolescents in the low tea and high soda (LH) group (ß = 0·05, P = 0·034) had significantly higher mean serum uric acid values. In conclusion, sugary tea remains the SSB of choice for Taiwanese adolescents. Those with a frequent intake of soda/sports/energy drinks had a higher chance of being hyperuricaemic.

Predictive value of combining the SYNTAX score with reactive hyperemia index in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

OBJECTIVE: To investigate the predictive value of SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score (SS) combined with reactive hyperemia index (RHI) in predicting 2-year major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Both SS and RHI are good predictors of MACE; however, it is unknown whether combining SS and RHI could improve predictability of MACE in patients with ACS undergoing PCI. METHODS: We undertook a prospective study in 401 ACS patients that underwent PCI. The RHI-SYNTAX score (RSS) was calculated by categorizing and summing up the RHI and SS of individual patients. Patients with RHI < 1.67 are given 1 point, RHI ≥ 1.67 given 0 points, and those with SS ≤ 22 scored as 0 and SS > 22 as 1 point. Patients were classified into three groups: low RSS (group 0), moderate RSS (group 1), and high RSS (group 2). RESULTS: Among patients in the low, moderate, and high groups, the 2-year rates of MACE were 5.50, 10.66, and 23.33%, respectively (p < .0001). Total revascularization rates were 1.83, 2.54, and 8.89%, respectively (p = .015). Ischemic stroke rates were 0.00, 3.67, and 5.56%, respectively (p = .031). By multivariate analysis, the RSS was an independent predictor of 2-year MACE (hazard ratio: 2.09, 95% CI: 1.36-3.21, p = .001). Receiver-operator characteristic analysis indicated that the area under the curve significantly improved from 0.63 to 0.69, when RHI was added to SS (p < .0001). CONCLUSIONS: RSS is correlated with 2-year MACE in patients presenting with ACS undergoing PCI.

[One-stage posterior correction and second-stage anterior debridement and fusion in treating children with thoracic tuberculosis complicated with kyphoscoliosis].

Objective: To investigate the clinical outcomes of one-stage posterior correction surgery and second-stage anterior debridement and fusion in treating children with thoracic tuberculosis complicated with kyphoscoliosis. Methods: From January 2008 to December 2014, a total of 17 children with thoracic vertebral tuberculosis complicated with kyphoscoliosis who underwent a one-stage posterior correction and second-stage anterior debridement and complementary fusion were included. There were 8 males and 9 females with an average age of (8±4) years (5-14 years). All patients underwent posterior correction and anterior debridement and bone graft fusion surgery. The neurological function was determined by Frankel grade. The operation time, estimated blood loss (EBL), levels fused and numbers of screws were recorded. The following radiographic parameters were measured: Cobb angle of the coronal curve, regional kyphosis and sagittal vertical axis (SVA). The incidence of intraoperative and postoperative complications was recorded. The data before and after the operation were compared with paired sample t test. Results: The tuberculosis lesions located in the thoracic vertebrae, and the abscess involved 2 to 4 vertebral segments. The average operation time was (4.1±0.8) h, the EBL was (526±275) ml, the levels fused were 7.6±2.3, and 173 pedicle screws were placed. The preoperative coronal curve averaged 12.6°±6.2°, and it was corrected to 4.2°±1.9° postoperatively (t=4.628, P<0.01), the regional kyphosis was 67.2°±19.4°, and it was corrected to 15.7°±8.2° postoperatively (t=8.192, P<0.01). The SVA improved from (8.1±5.0) mm to (3.0±1.7) mm postoperatively. The mean duration of follow-up for all the patients were (38±11) months. At final follow-up, SVA was reduced to (2.4±2.0) mm and the other parameter kept stable. Thirteen patients had more than one grade improvement of Frankel grade. The VAS score for all patients improved from 4.7±2.8 to 2.2±0.5 postoperatively (t=3.973, P=0.01), and improved to 0.5±0.5 at final follow-up (t=-7.880, P<0.01). No recurrence of primary spinal tuberculosis was seen at final follow-up of all patients. Conclusions: One-stage posterior correction and second-stage anterior complementary debridement and fusion is an effective procedure for children with thoracic tuberculosis complicated with kyphoscoliosis. Significant postoperative deformity correction could be achieved with satisfactory improvement of neurological function. Solid fusion and satisfactory correction maintenance were observed at mid-to long-term follow-up.