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Objective. To evaluate the effectiveness and safety of transarterial chemoembolization (TACE) combined with immune checkpoint inhibition (camrelizumab) plus an antiangiogenic agent (apatinib) for advanced hepatocellular carcinoma (HCC). Methods. Between March 2019 and April 2021, the clinical data of 38 patients diagnosed with advanced HCC who initially received TACE combined with camrelizumab plus apatinib were reviewed retrospectively. The objective response rate (ORR) and disease control rate (DCR) according to modified response evaluation criteria in solid tumors, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. Results. At 2-3 months after initial therapy, the ORR and DCR was 50.0% (19/38) and 76.3% (29/38), respectively. The median PFS and OS were 7.3 months (range: 1.0–22.6 months) and 13.5 months (range: 2.3–24.3 months), respectively. Treatment-related AEs (grades 3-4) were observed in 25 patients (67.8%). No treatment-related deaths occurred. Conclusion. The combination of TACE with camrelizumab plus apatinib for the treatment of patients with advanced HCC showed promising efficacy and a manageable safety profile.

Purpose To determine the ability of prostatic artery embolization (PAE) to achieve freedom from catheterization in patients with acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH). Materials and Methods This retrospective single-center study was performed between June 2014 and March 2019 in patients with lower urinary tract symptoms (LUTS) caused by BPH. PAE was performed in 154 eligible patients, of which 76 suffered from spontaneous AUR and had indwelling catheters placed and kept until the procedure, owing to clinical failure in the removal of the previous intermittent catheter. Each patient was followed for at least 12 months. The first trial without catheter was performed 3 days after PAE. Successful catheter removal within the first 30 days after PAE was considered a clinical success. The rate of patients free from catheterization, LUTS relief, prostate volume, and adverse events was recorded. Results Clinical success was achieved in 70 (92.1%) patients. The rates of freedom from catheterization were 90.3% (65/72), 83.3% (60/72), and 80.6% (58/72) at 3-, 6-, and 12-months follow-up, respectively. The median elapsed time from PAE to catheter removal was 10 days. However, 18 patients needed further interventions. Symptom scores revealed a continuous improvement in urinary symptoms. The mean prostate volume showed a statistically significant decrease at 3 and 12 months compared with its baseline value. No severe adverse events occurred. Conclusions PAE can achieve freedom from catheterization in patients with AUR caused by BPH.

Background PRP injection was proved to promote the health condition of individuals with mild to moderate Carpal Tunnel Syndrome (CTS). However, carpal tunnel release (CTR) was still a necessary treatment for individuals with moderate and severe CTS. Methods To explore whether adjuvant PRP treatment would improve the prognosis while using CTR, we included 82 patients in this study. Preoperative and postoperative visual analog scale (VAS), Boston carpal tunnel syndrome questionnaire-symptom severity scale (BCTQ-SSS), Boston carpal tunnel syndrome questionnaire-functional status scale (BCTQ-FSS), and grip strength were used to examine the patient's symptoms and function. Results CTR combined with PRP treatment improved the VAS (1.9 ± 0.5 versus 1.4 ± 0.4, P P P Conclusions PRP does not affect long-term prognosis while increasing the surgery cost. To conclude, PRP as an adjuvant treatment of CTR has limited effect. Considering the additional financial burden on patients, CTR combined with PRP should be cautious in CTS treatment.

To evaluate the safety and efficacy of prostatic artery embolization (PAE) in patients with recurrent lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) who underwent a previous transurethral resection of the prostate (TURP).This retrospective study analyzed 15 of 19 patients who underwent PAE for recurrent LUTS after TURP between February 2014 and April 2019. The technical and clinical success rates and complications related to the procedure were recorded. International Prostate Symptom Score (IPSS), quality of life (QoL), and prostatic volume (PV) were evaluated at baseline and 3- and 12-mo follow-up.The intervals from TURP to recurrent symptoms and from TURP to PAE were 4.3 y ± 3.2 and 5.6 y ± 3.8, respectively. Technical success was achieved in all patients. The clinical success rate for LUTS relief at 12 mo was 93.3% (14 of 15). IPSS significantly reduced from 22.5 ± 4.1 at baseline to 9.9 ± 4.9 at 12-mo follow-up, and QoL score improved from 4.7 ± 1.0 to 2.1 ± 1.1 (P.05 for both). There was a significant mean reduction of 26.6% in PV at 12 mo, improving from 100.7 cmPAE may be a safe and effective treatment option for the management of recurrent LUTS secondary to BPH in patients who have previously undergone TURP.

BackgroundThere are few studies on predictive biomarkers for hyperuricemia, and the predictive value of these biomarkers tends to be poor. Additionally, no reports have described the predictive value of retinol binding protein 4 (RBP4) for hyperuricemia.PurposeThis study was performed to evaluate the value of RBP4 for predicting the risk of hyperuricemia in a general population, determine whether RBP4 could be used alone or in combination with other factors to predict the risk of hyperuricemia in the general population, and establish an optimum predictive model.MethodsWe conducted a population-based cross-sectional survey in 2018, involving a questionnaire, physical examination, and laboratory testing. We enrolled 2303 individuals by stratified random sampling, and 2075 were included in the data analysis after applying the eligibility criteria.ResultsSerum RBP4 level had a highly significant association with hyperuricemia (PPPConclusionsRBP4 is strongly associated with hyperuricemia, and its predictive value was higher than that of traditional predictors.

Excess levels of chemical hepatotoxicants (alcohol, aflatoxin B1), oxidative drugs (acetaminophen) and some cytokines (ET-1, TGF-β1) can induce chronic or acute liver injury. After these, the severe hepatic disease, especially the liver fibrosis (LF) occurs without taking measures, which brings threat to human health. The dibenzocyclooctadiene lignans of S. chinensis (SCDLs) were found to act as the hepatoprotective components via blocking endothelin B receptor (ETBR). While study on its anti-LF mechanisms especially for its refined compound of schisantherin D (SC-D) is still a lack. So this study aims to investigate the anti-fibrosis effect of SC-D with in vitro and in vivo assays. Bioinformatics analysis revealed the close relations of ETBR to Smad2, Smad3, Nrf2, etc. in LF-related signaling pathways (such as TGF-β/Smad and Nrf2/ARE). Histopathological staining on livers showed the recovery trend in SC-D treated LF mice. SC-D also modulated expressions of ETBR and fibrosis or anti-oxidative related proteins (such as TIMP1, p-Smad2/3, Nrf2, Smad7, etc.) in LF mice livers. Serum levels of TNF-α, COLI, ALT, AST and LDH in SC-D treated mice were also downregulated compared with LF mice, and upregulated expression of GSH. In vitro studies, SC-D also modulated expressions of LF-related proteins to the normal tendency in LX-2 cell, while weakened its anti- LX-2 proliferation effect by transfections of si-Smad7 or si-Nrf2. Accordingly the anti-LF approach of SC-D showed relations with modulating ETBR linked fibrosis and anti-oxidative related signaling. Also, Smad7 and Nrf2 might be the key factors for SC-D mediated anti-LF effect.

Background and objectivesCerebrospinal fluid (CSF) and interstitial fluid exchange along a brain-wide network of perivascular spaces (PVS) termed the ‘glymphatic system’. The aquaporin-4 (AQP4) water channels abundantly expressed on astrocytic endfeet play a key role in the CSF circulation in the glymphatic system. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS) featured with a specific autoantibody directed against AQP4 in most of patients. Anti-AQP4 antibodies are likely resulting in the impairment of the brain glymphatic system and the enlargement of PVS in NMOSD patients. In the current study, we aimed to demonstrate the features of EPVS detected by MRI and its association with the CSF anti-AQP4 antibody titer, CNS inflammatory markers, and disease severity in NMOSD patients.MethodsWe conducted a retrospective review of a consecutive cohort of 110 patients with NMOSD who had brain MRI. We assessed the correlation of EPVS with markers of neuroinflammation, blood-brain barrier (BBB) function and severity of neurological dysfunction in patients. We used multivariate logistic regression analysis to determine the independent variables associated with disease severity.ResultsThe median number of total-EPVS was 15.5 (IQR, 11-24.2) in NMOSD patients. The number of total-EPVS was significantly related to EDSS score after correcting for the effects of age and hypertension (r=0.353, pDiscussionIn our cohort, we found a relationship between EPVS and neuroinflammation and BBB function in NMOSD. Moreover, EPVS might independently predict neurological dysfunction in patients with NMOSD.

Apurinic endonuclease 1 (APE1) has been suggested as an oncogene of lung tumours and our bioinformatics analysis identified the association between Erlotinib resistance and interleukin-6 (IL-6). Thus, we performed this work to delineate the mechanistic actions of APE1/IL-6 signalling in Erlotinib resistance of non-small cell lung cancer (NSCLC).We selected human NSCLC cell lines HCC827 and PC9 to establish Erlotinib-resistant HCC827R and PC9R cells. Cancer stem cells (CSCs) were isolated from Erlotinib-sensitive HCC827P and PC9P cells (PCSCs) and from HCC827R and PC9R cells (RCSCs). Further, extracellular vesicles (EVs) were separated from PCSCs (PCSC-EVs) and RCSCs (RCSC-EVs) and co-cultured with RCSCs with or without short hairpin RNA (shRNA)-targeting APE1 (APE1 shRNA) transduction. In addition, functional assays were conducted to determine the effect of APE1 shRNA on malignant phenotypes of cancer cells in vitro and in vivo and the activation of IL-6/STAT3 signalling.It was found that NSCLC cells could internalize both RCSC-EVs and PCSC-EVs. RCSC-EVs augmented the resistance of NSCLC cells to Erlotinib. The overexpression of APE1 occurred in NSCLC tissues, and IL-6 was enriched in serum samples of patients with NSCLC. APE1 shRNA was demonstrated to restrict the Erlotinib resistance of NSCLC cells by inactivating the IL-6/STAT3 signalling. Additionally, shAPE1-loaded RCSC-EVs suppressed the Erlotinib resistance of NSCLC via the IL-6/STAT3 axis both in vitro and in vivo, as reflected by impeded malignant phenotypes and xenograft tumour formation.Collectively, these data indicate that APE1 confers Erlotinib resistance by activating the IL-6/STAT3 signalling, suggesting targeting APE1 as a possible therapeutic target in Erlotinib-resistant NSCLC.

To explore the efficacy of prostatic artery embolization (PAE) for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) during long-term follow-up and analyze predictors related to LUTS recurrence.This was a single-center retrospective study involving 125 BPH patients with LUTS who underwent PAE from February 2014 to February 2020. The median follow-up was 36 months. Clinical success was defined as reductions in the International Prostate Symptom Score (IPSS) and quality of life (QoL) score and no need for any other treatment for LUTS; otherwise, it was regarded as a clinical failure. Recurrence was defined as a clinical failure that occurred after an initial success. Cumulative clinical success rates, recurrence rates and re-intervention rates were evaluated. Friedman test was performed to compare differences in IPSS, QoL and prostatic volume (PV) among baseline and follow-up times. Predictors for LUTS recurrence were analyzed with the univariate and multivariate Cox regression model.Technical success (bilateral PAE) rate was 92.8% (116/125). Significant differences in IPSS, QoL and PV were observed between baseline and follow-up time points (P 0.001). The cumulative clinical success rates at 2, 3, 4 and 5 years were 82.4%, 65.5%, 52.4% and 37.4%. The cumulative recurrence rates and re-intervention rates at 1, 2 and 5 years were 6.8%, 12.7%, 60.4% and 5.9%, 10.2%, 50.8%, respectively. Unilateral PAE was an significant predictor of recurrence (P 0.05).PAE is an effective treatment option for LUTS. Unilateral PAE is a significant independent predictor of LUTS recurrence.

Background: Persistent infection with the high-risk of human papillomavirus (HR-HPVs) is the primary etiological factor of cervical cancer; HR-HPVs express oncoproteins E6 and E7, both of which play key roles in the progression of cervical carcinogenesis. Zinc Finger Nucleases (ZFNs) targeting HPV E7 induce specific shear of the E7 gene, weakening the malignant biological effects, hence showing great potential for clinical transformation. Objective: Our aim was to develop a new comprehensive therapy for better clinical application of ZFNs. We here explored the anti-cancer efficiency of HPV targeted ZFNs combined with a platinum-based antineoplastic drug Cisplatin (DDP) and an HDAC inhibitor Trichostatin A (TSA). Methods: SiHa and HeLa cells were exposed to different concentrations of DDP and TSA; the appropriate concentrations for the following experiments were screened according to cell apoptosis. Then cells were grouped for combined or separate treatments; apoptosis, cell viability and proliferation ability were measured by flow cytometry detection, CCK-8 assays and colony formation assays. The xenograft experiments were also performed to determine the anti-cancer effects of the combined therapy. In addition, the HPV E7 and RB1 expressions were measured by western blot analysis. Results: Results showed that the combined therapy induced about two times more apoptosis than that of ZFNs alone in SiHa and HeLa cells, and much more inhibition of cell viability than either of the separate treatment. The colony formation ability was inhibited more than 80% by the co-treatment, the protein expression of HPV16/18E7 was down regulated and that of RB1 was elevated. In addition, the xenografts experiment showed a synergistic effect between DDP and TSA together with ZFNs. Conclusion: Our results demonstrated that ZFNs combined with DDP or TSA functioned effectively in cervical cancer cells, and it provided novel ideas for the prevention and treatment of HPV-related cervical malignancies.

Sarcopenia is emerging as a prognostic factor in patients with malignant diseases. The prognostication of perihilar cholangiocarcinoma (PHC) with obstructive jaundice was complex, because these patients suffered compete mortality events beyond cancer itself. Our study was to investigate the association between low skeletal-muscle index and overall survival (OS) after percutaneous transhepatic biliary drainage (PTBD) for obstructive jaundice due to PHC. We performed a retrospective survival analysis of patients undergoing PTBD for PHC-related obstructive jaundice between January 2016 and March 2019. Using computed tomography, we measured skeletal-muscle mass at the third lumbar vertebra (L3) to obtain a skeletal-muscle index (SMI). Then, we compared OS between low- and high-SMI groups. Furthermore, factors that could potentially affect OS were assessed. One hundred and four patients (56 males; mean age 66 ± 12 years) were analyzed. Median OS after PTBD was 150 days. OS was shorter in patients with low SMI than in those with high SMI (median OS, 120 vs. 270 days; P

To compare the feasibility and efficacy of emergency transarterial embolization (TAE) followed by staged hepatectomy (SH) with emergency hepatectomy (EH) for ruptured hepatocellular carcinoma (HCC). Between January 2012 and December 2017, 102 patients with HCC rupture received EH or emergency TAE followed by SH in our center. Patients were followed until April 2019. Propensity score matching (PSM) analysis was used at a 1:2 ratio, resulting in 20 patients in the SH group and 40 patients in the EH group. We retrospectively compared the operative variables, recurrence status, disease-free survival (DFS), and overall survival (OS) of patients between the two matched groups. Compared with the matched EH group, the SH group showed significantly decreased perioperative blood loss or blood transfusion, shortened intraoperative duration of clamping and postoperative hospital stay (P

PURPOSE: We aimed to identify the treatment options and prognostic factors for patients with initially unresectable ruptured hepatocellular carcinoma (HCC). METHODS: Between June 2012 and December 2016, 94 consecutive patients with initially unresectable ruptured HCC were analyzed retrospectively. Patients were followed until December 2017. Predictors of short-term (≤30 days) and long-term (>30 days) survival were identified by using logistic regression model and Cox proportional hazard model, respectively. RESULTS: Of the 94 patients, initial hemostasis was achieved by transarterial embolization (TAE) in 59 patients, surgical hemostasis in 14 patients, and conservative treatment in 21 patients. Twenty-five (26.6%) patients died within 30 days of tumor rupture. In the multivariate analysis, patients treated with aggressive initial treatment strategies (TAE or surgical hemostasis) (P < 0.001) or those with better Child-Pugh class (P = 0.003) and absence of shock on admission (P = 0.001) had a better chance of short-term survival. For 69 patients who survived more than 30 days after initial treatment, the median survival time was 268 days. In the multivariate analysis, among the 69 who survived, early modified LCSGJ stage (P = 0.003) and staged hepatectomy as definitive treatment (P < 0.001) were significant predictors of increased long-term survival. CONCLUSION: Short-term survival of patients with initially unresectable ruptured HCC could be achieved in the presence of better Child-Pugh class, absence of shock, and with the use of aggressive initial treatment strategies. Among survivors of the emergency phase of tumor rupture, long-term survival was significantly increased with early modified LCSGJ stage and staged hepatectomy therapy.

Background The type I human interferon (IFN) family consists of a group of cytokines with a multiplicity of biological activities, including antiviral, antitumor, and immunomodulatory effects. However, because the half-life of IFN is short, its clinical application is limited. Increasing the yield and biological activity of IFN while extending its half-life is currently the focus of IFN research. Results Two novel long-acting recombinant human IFN-α2b (rhIFN-α2b) proteins were designed in which the carboxyl-terminal peptide (CTP) of the human chorionic gonadotropin β su bunit and N-linked glycosylation sequences were linked to rhIFN-α2b. They were designated IFN-1CTPON (fused at the C-terminus of rhIFN-α2b) and IFN-2CTPON (fused at both the C-terminus and N-terminus of rhIFN-α2b). Monoclonal CHO cell strains stably and efficiently expressing the IFNs were successfully selected with methotrexate (MTX), and the highest expression levels were 1468 mg/l and 1196 mg/l for IFN-1CTPON and IFN-2CTPON, respectively. The proteins were purified with affinity chromatography and molecular sieve chromatography. IFN-1CTPON and IFN-2CTPON showed antiviral and antiproliferative activities in vitro. Notably, the half-life of IFN-1CTPON and IFN-2CTPON in vivo were three-fold and two-fold longer than that of commercially available rhIFN-α2b. Conclusions CHO cell strains stably expressing long-acting rhIFN-α2b were screened. The purified IFN-CTPON protein has biological activity and an extended half-life, and therefore potential applications.

Although 5-methylcytosine (m5C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m5C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m5C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m5C 'reader' recognizing m5C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m5C methylation site in the HDGF 3' untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m5C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.

Our objective was to assess the impact of hs-cTnT elevation on functional outcome and mortality in AIS patients with large vessel occlusion (LVO) in the anterior circulation 3 months after ET and explore factors affecting hs-cTnT elevation. A total of 143 consecutive AIS patients with large vessel occlusion (LVO) in the anterior circulation following ET in a single stroke center were enrolled between January 2015 and November 2017. Hs-cTnT was quantitated on admission. Demographic characteristics, clinical data, functional outcome and all-cause mortality were compared between patients with elevated hs-cTnT levels (14 ng/L) and those with normal hs-cTnT levels (≤14 ng/L). 58/143(40.6%) patients showed elevated hs-cTnT levels before ET. Factors independently associated with hs-cTnT elevation were admission NIHSS score (OR = 1.08, 95% CI 1.01-1.16, p = 0.032), coronary heart disease (OR = 4.89, 95% CI 1.82-13.11, p = 0.002) and congestive heart failure (OR = 4.10, 95% CI 1.07-15.68, p = 0.039). In the univariate analysis, patients with elevated hs-cTnT levels were at significantly higher risk of 3-month poor outcome (p = 0.029) and mortality (p 0.001) than those with normal hs-cTnT levels. After multivariable analysis, hs-cTnT elevation remained an independent predictor of 3-month mortality (OR = 4.49, 95% CI 1.68-11.98, p = 0.003). In this cohort of AIS patients with LVO in the anterior circulation undergoing ET, hs-cTnT elevation is an independent predictor of 3-month mortality. Admission NIHSS score, coronary heart disease and congestive heart failure are independently associated with elevated hs-cTnT levels.

BackgroundDry eye is often the first presenting manifestation of primary Sjögren’s syndrome (pSS). Because of the high prevalence of dry eye disease in normal population, ophthalmologists urgently need a non-invasive and reliable screening test to diagnose dry eye associated SS patients, other than ocular symptoms and signs. Currently, there is no single test available. The correlation of serum IL-14α with pSS has been found in pSS mouse model.PurposeTo evaluate whether IL-14α can serve as a biomarker to stratify dry eye in primary Sjögren’s syndrome and its correlation to BAFF in a cohort of patients with non-SS dry eye (NSDE), pSS with dry eye disease, rheumatoid arthritis (RA), and healthy controls (HC).MethodsRetrospective study based on serum levels of IL-14α (defined by Western Blot) and BAFF (measured by ELISA) were evaluated among pSS with dry eye disease, NSDE, RA, and HC groups. Serum levels of SS related autoantibodies (Ro, La, SP1, PSP, and CA6) were also measured by ELISA.ResultsOne hundred and eighty patients were included for the current study, patients were separated into four groups as defined by pSS (n=65), NSDE (n=20), RA (n=50) and HC (n=45). The level of serum IL-14α in pSS was significantly higher compared to NSDE, RA, and HC (p=0.0011, p=0.0052 and pConclusionsThis is the first paper to report both IL-14α and BAFF could serve as a critical cytokine biomarker for the stratification of dry eye in primary Sjögren’s syndrome. This may help ophthalmologists to develop non-invasive metrics for the diagnosis of dry eye associated pSS.

Ferroptosis is critically involved in the pathophysiology of diabetic nephropathy (DN). As a bioactive peptide, salusin-β is abundantly expressed in the kidneys. However, it is unclear whether salusin-β participates in the pathologies of diabetic kidney damage by regulating ferroptosis. The present study found that high glucose (HG) treatment upregulated the protein expressions of salusin-β in a dose- and time-dependent manner. Genetic knockdown of salusin-β retarded, whereas overexpression of salusin-β aggravated, HG-triggered iron overload, antioxidant capability reduction, massive reactive oxygen species production and lipid peroxidation in HK-2 cells. Mechanistically, salusin-β inactivated nuclear factor erythroid-derived 2-like 2 (Nrf-2) signaling, thus contributing to HG-induced ferroptosis-related changes in HK-2 cells. Notably, the protein expression of salusin-β was upregulated by ferroptosis activators, such as erastin, RSL3, FIN56 and buthionine sulfoximine. Pretreatment with ferrostatin-1 (a ferroptosis inhibitor) prevented the upregulated protein expression of salusin-β in HK-2 cells exposed to HG. Taken together, these results suggested that a positive feedback loop between salusin-β and ferroptosis primes renal tubular cells for injury in diabetes.

Background Gestational diabetes mellitus (GDM) is a common endocrine metabolic disease, involving a carbohydrate intolerance of variable severity during pregnancy. The incidence of GDM-related complications and adverse pregnancy outcomes has declined, in part, due to early screening. Machine learning (ML) models are increasingly used to identify risk factors and enable the early prediction of GDM. Objective The aim of this study was to perform a meta-analysis and comparison of published prognostic models for predicting the risk of GDM and identify predictors applicable to the models. Methods Four reliable electronic databases were searched for studies that developed ML prediction models for GDM in the general population instead of among high-risk groups only. The novel Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess the risk of bias of the ML models. The Meta-DiSc software program (version 1.4) was used to perform the meta-analysis and determination of heterogeneity. To limit the influence of heterogeneity, we also performed sensitivity analyses, a meta-regression, and subgroup analysis. Results A total of 25 studies that included women older than 18 years without a history of vital disease were analyzed. The pooled area under the receiver operating characteristic curve (AUROC) for ML models predicting GDM was 0.8492; the pooled sensitivity was 0.69 (95% CI 0.68-0.69; P Conclusions Compared to current screening strategies, ML methods are attractive for predicting GDM. To expand their use, the importance of quality assessments and unified diagnostic criteria should be further emphasized.

To evaluate the safety and efficacy of superselective vesical artery embolization (SVAE) in the treatment of intractable hemorrhagic cystitis (HC) following hematopoietic stem cell transplantation (HSCT). From January 2010 to December 2018, 26 patients with hematologic malignancy who underwent SVAE for treatment of intractable HC following HSCT were retrospectively reviewed. SVAE was performed with 300–500 μm gelatin-sponge particles initially. Technical success was defined as achieving bilateral SVAE for all the prominent vesical arteries. Therapeutic efficacy was defined as: Complete response (CR): macroscopic hematuria completely disappeared on more than 2 consecutive days after SVAE; Partial response (PR): macroscopic hematuria reduced after SVAE or briefly disappeared after SVAE but reappeared soon within 2 days; No response: no response to SVAE or hematuria aggravated after SVAE; Recurrence: macroscopic hematuria relapsed on follow-up after achieving an initial CR. Adverse events were also registered. There was a mean follow-up of 11.4 months (range, 0.5–83.7). The mean interval for the onset of HC after HSCT was 39.7 ± 19.0 days, and mean duration of hematuria before embolization was 14.9 ± 15.7 days. SVAE was technically successful in all patients. After embolization, macroscopic hematuria regressed within 48 h for all patients. The mean urine erythrocyte counts dropped from 14,213.2 ± 20,999.0/uL before SVAE to 6072.9 ± 12,720.7/uL on 3d after SVAE (P = 0.002) and 3720.2 ± 8988.9/uL on 7 d after SVAE (P = 0.001), respectively. Hematuria completely disappeared prior to discharge in 23 (88.5%) patients (including 20 with one embolization and 3 with 2 embolizations) and remainder 3 patients had PR. No major procedure-related complications were noted, except for post-embolization syndrome in 8 patients, which resolved with symptomatic treatment. On follow-up monthly, hematuria recurrence was seen in 4/23 patients (17.4%) and was managed conservatively in 2 patients and with repeat embolization in the remainder 2 patients. For fragile patients with hematologic malignancy, SVAE is safe and effective to treat HC following HSCT, even though repeat embolization may be required to achieve a sustained complete remission of the hematuria.

Integration of high-risk HPV genomes into cellular chromatin has been confirmed to promote cervical carcinogenesis, with HPV16 being the most prevalent high-risk type. Herein, we evaluated the therapeutic effect of the CRISPR/Cas9 system in cervical carcinogenesis, especially for cervical precancerous lesions. In cervical cancer/pre-cancer cell lines, we transfected the HPV16 E7 targeted CRISPR/Cas9, TALEN, ZFN plasmids, respectively. Compared to previous established ZFN and TALEN systems, CRISPR/Cas9 has shown comparable efficiency and specificity in inhibiting cell growth and colony formation and inducing apoptosis in cervical cancer/pre-cancer cell lines, which seemed to be more pronounced in the S12 cell line derived from the low-grade cervical lesion. Furthermore, in xenograft formation assays, CRISPR/Cas9 inhibited tumor formation of the S12 cell line in vivo and affected the corresponding protein expression. In the K14-HPV16 transgenic mice model of HPV-driven spontaneous cervical carcinogenesis, cervical application of CRISPR/Cas9 treatment caused mutations of the E7 gene and restored the expression of RB, E2F1, and CDK2, thereby reversing the cervical carcinogenesis phenotype. In this study, we have demonstrated that CRISPR/Cas9 targeting HPV16 E7 could effectively revert the HPV-related cervical carcinogenesis in vitro, as well as in K14-HPV16 transgenic mice, which has shown great potential in clinical treatment for cervical precancerous lesions.

Background Currently, the percutaneous approach is the mainstream of treatment for malignant bilioenteric anastomotic stricture (BAS). However, there is no consensus on the optimal bile drainage method since previous studies on malignant BAS related jaundice are very limited. The purpose of the study is to compare self-expandable metallic stent placement with catheter drainage for malignant bilioenteric anastomotic stricture in terms of efficacy and safety. Materials and Methods This study included 54 patients with malignant bilioenteric anastomotic stricture treated from March 2016 to February 2020. Twenty-seven patients underwent insertion of self-expandable metallic stent (Stent group); the remaining twenty-seven patients underwent internal-external catheter drainage (Catheter group). Technical success was defined as successful placement of stent or drainage catheter in the appropriate position; clinical success was defined as a 20% reduction in serum bilirubin within 1 week after the procedure, compared with baseline. Complications, duration to stent/catheter malfunction, and overall survival were evaluated. Results Technical success was achieved in all patients in both groups. In the Stent group, 21 patients received one stent and the other 6 patients required two stents. Clinical success rates were similar between the groups (Stent group, 92.6% [25/27]; Control group, 88.9% [24/27]). There were no major complications. The median duration to stent/catheter malfunction was significantly longer in the Stent group (130 days) than in the Control group (82 days; P = 0.010). The median overall survival was also significantly longer in the Stent group (187 days) than in the Catheter group (118 days; P = 0.038). Conclusion Self-expandable metallic stent placement may be better than internal-external catheter drainage for malignant bilioenteric anastomotic stricture in terms of the duration before stent/catheter malfunction and patient survival.

Background: With the spread of Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, its effect on society is amplified. We aimed to describe the viral detection results across different timepoints throughout the disease course. Methods: A retrospective study of 301 confirmed COVID-19 patients hospitalized at Tongji Hospital in Wuhan, China, were included. Demographic characteristics of the patients were collected. Upper respiratory specimens (throat and/or nasal swabs) were obtained and analyzed by real-time RT-PCR for SARS-CoV-2 infection. Period of viral infection and the contagious stage were analyzed. Results: Of 301 hospitalized COVID-19 patients, the median age was 58 years and 51.2% were male. The median period between symptoms presence and positive SARS-CoV-2 RT-PCR results was 16 days (IQR, 10-23, N=301). The median period between symptoms presence and an effective negative SARS-CoV-2 RT-PCR result was 20 days (IQR, 17-24; N=216). Infected patient ≥65 years old stayed contagious longer (22 days vs 19 days, p=0.015). Although two consecutive negative results were confirmed in 70 patients, 30% of them had positive viral test results for the third time. Using specimens from nasal swabs to run the RT-PCR test showed a higher positive rate than using specimens from throat swabs. Conclusions: This large-scale investigation with 1113 RT-PCR test results from 301 COVID-19 patients showed that the average contagious period of SARS-CoV-2 infected patients was 20 days. Longer observation period and more than 2 series of negative viral test are necessary for patients ≥65 years. Funding Statement: No funding resources to declare for this study. Declaration of Interests: All authors declare that there are no conflicts of interest. Ethics Approval Statement: This study was approved by the Ethics committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Background. Insulin receptor substrate 1 (IRS-1) is an important molecule of the insulin signal transduction pathway and has been associated with the occurrence and development of many tumors, including hepatocellular carcinoma (HCC). Our study was designed to determine the expression and significance of IRS-1 in human HCC. Methods. Two hundred and forty specimens were drawn from 140 patients, including 100 HCC tissues and 100 paracancerous (PC) tissues from 100 HCC patients, 20 liver cirrhosis (LC) tissues from 20 LC patients, and 20 chronic hepatitis (CH) tissues from 20 CH patients. Baseline and pathological characteristics were included, and the expression of IRS-1 was examined by immunohistochemical (IHC) staining. Binary logistic regression model calculation was used for multivariate analysis. Results. The total positive rates of IRS-1 expression were 41.0%, 17.0%, 15.0%, and 10.0% in HCC, PC, LC and CH tissues, respectively. IRS-1-positive signals were brown in color and located in the nucleus and cytoplasm. Compared with PC, LC, and CH tissues, a significantly increased expression was observed in human HCC tissues (P<0.001, P=0.028, and P=0.008). Eight of the total 240 specimens had the strong immunostaining of IRS-1 expression, and all of them were HCC tissues. After control of the age, gender, and HBV and HCV infection, IRS-1 expression was independently associated with the diagnosis of HCC (OR 6.60, 95% CI 2.243-19.425, P=0.001). Conclusions. Positive expression of IRS-1 in HCC was increased significantly and may play an important role in the occurrence and development of human HCC.

To evaluate the efficacy and prognostic factors following transarterial embolization (TAE) as initial treatment for spontaneously ruptured hepatocellular carcinoma (HCC). From June 2012 to June 2016, a total of 57 spontaneously ruptured HCC patients who received TAE as initial therapy were retrospectively studied at our institution. Patients were followed until October 2016. Survival rates were estimated using the Kaplan–Meier method, and prognostic factors related to survival were evaluated using Cox regression analysis. Among them, 8 (14.0%) patients died within 30 days after initial TAE. The median overall survival time was 208 days. The 6-month, 1-year, and 2-year cumulative overall survival rates were 50.3%, 35.9%, and 14.7%, respectively. Multivariate analysis indicated that tumor size [HR (hazard ratio) 1.12; 95% CI (confidence interval) 1.02–1.23, P = 0.022] Child–Pugh class (HR 1.78; 95% CI 1.13–2.80; P = 0.013), absence of shock on admission (HR 0.40; 95% CI 0.17–0.95; P = 0.039), and embolization with lipiodol and gelatin sponge particles (HR 0.33; 95% CI 0.16–0.70; P = 0.004) were independent prognostic factors for survival. TAE appeared to be an effective initial treatment for spontaneously ruptured HCC. The results indicated that large tumors, poor Child–Pugh class, and shock on admission were associated with poor prognosis. For these patients, embolization with lipiodol and gelatin sponge particles could achieve better survival than PVA particles used.

BackgroundPrevious studies suggest that recurrence of hemoptysis after arterial embolization is associated with the underlying pulmonary disease.PurposeTo compare the baseline information and imagi...

Persistent high-risk HPV infection is the main cause of cervical cancer. The HPV oncogene E7 plays an important role in HPV carcinogenesis. Currently, HPV vaccines do not offer an effective treatment for women who already present with cervical disease, and recommended periodical cervical screenings are difficult to perform in countries and areas lacking medical resources. Our aim was to develop nanoparticles (NPs) based on poly (β-amino ester) (PBAE) and HPV16 E7-targeting CRISPR/short hairpin RNA (shRNA) to reduce the levels of HPV16 E7 as a preliminary form of a drug to treat HPV infection and its related cervical malignancy. Our NPs showed low toxicity in cells and mouse organs. By reducing the expression of HPV16 E7, our NPs could inhibit the growth of cervical cancer cells and xenograft tumors in nude mice, and they could reverse the malignant cervical epithelium phenotype in HPV16 transgenic mice. The performance of NPs containing shRNA is better than that of NPs containing CRISPR. HPV-targeting NPs consisting of PBAE and CRISPR/shRNA could potentially be developed as drugs to treat HPV infection and HPV-related cervical malignancy.

Non-small-cell lung cancer (NSCLC), the most common type of lung cancer accounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymethylcytosine (5hmC) signatures in circulating cell-free DNA (cfDNA) that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminating tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here, we employed a sensitive and reliable method to map genome-wide 5hmC in the cfDNA of Chinese NSCLC patients and detected a significant 5hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identified six potential biomarkers from 66 patients and 67 healthy controls (mean decrease accuracy >3.2, P

Ubiquitin-specific protease 22 (USP22) is a member of the "death-from-cancer" signature, which plays a key role in cancer progression. Previous evidence has shown that USP22 is overexpressed and correlates with poor prognosis in glioma. The effect and mechanism of USP22 in glioma malignancy, especially cancer stemness, remain elusive. Herein, we find USP22 is more enriched in stem-like tumorspheres than differentiated glioma cells. USP22 knockdown inhibits cancer stemness in glioma cell lines. With a cell-penetrating TAT-tag protein, B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), a robust glioma stem-cell marker, is found to mediate the effect of USP22 on glioma stemness. By immunofluorescence, USP22 and BMI1 are found to share similar intranuclear expression in glioma cells. By analysis with immunohistochemistry and bioinformatics, USP22 is found to positively correlate with BMI1 at the post-translational level only rather than at the transcriptional level. By immunoprecipitation and in vivo deubiquitination assay, USP22 is found to interact with and deubiquitinate BMI1 for protein stabilization. Microarray analysis shows that USP22 and BMI1 mutually regulate a series of genes involved in glioma stemness such as POSTN, HEY2, PDGFRA and ATF3. In vivo study with nude mice confirms the role of USP22 in promoting glioma tumorigenesis by regulating BMI1. All these findings indicate USP22 as a novel deubiquitinase of BMI1 in glioma. We propose a working model of the USP22-BMI1 axis, which promotes glioma stemness and tumorigenesis through oncogenic activation. Thus, targeting USP22 might be an effective strategy to treat glioma especially in those with elevated BMI1 expression.

Viral infections cause at least 10%-15% of all human carcinomas. Over the last century, the elucidation of viral oncogenic roles in many cancer types has provided fundamental knowledge on carcinogenetic mechanisms and established a basis for the early intervention of virus-related cancers. Meanwhile, rapidly evolving genome-editing techniques targeting viral DNA/RNA have emerged as novel therapeutic strategies for treating virus-related carcinogenesis and have begun showing promising results. This review discusses the recent advances of genome-editing tools for treating tumorigenic viruses and their corresponding cancers, the challenges that must be overcome before clinically applying such genome-editing technologies, and more importantly, the potential solutions to these challenges.

Objective To identify the risk factors for early and late relapse of haemoptysis after bronchial artery embolisation (BAE). Design We performed a retrospective study of 255 patients with haemoptysis who underwent BAE from January 2009 to June 2016 at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Using a Cox regression model, risk factors contributing to early (within the first month) and late (>1 month) recurrence were analysed. We censored recurrence-free patients at 1 month and patients without rebleeding after 1 month. Results The cumulative recurrence rate at 1, 6, 12, 24 and 48 months was respectively 14.9%, 16.9%, 20.6%, 31.0% and 39.9%, with a median follow-up of 574 days. Early relapse occurred in 38 of 255 patients, while late recurrence was found in 45 of the remaining 217 patients. The risk factors related to early recurrence were lung destruction on computed tomography of the chest and involvement of non-bronchial systemic arteries. The risk factors associated with late recurrence were tuberculosis sequelae, the presence of shunts and the use of gelfoam as an embolisation material. Conclusions The variables related to incomplete embolisation were the risk factors for early rebleeding. The variables associated with same-vessel recanalisation and formation of a new collateral circulation influenced late recurrence.

BACKGROUND Lower respiratory tract illness is a major cause of morbidity and mortality in children worldwide, however, information about the epidemiological and clinical characteristics of LRTIs caused by HMPV and HBoV in China is limited. OBJECTIVES Human bocavirus (HBoV) and human metapneumovirus (HMPV) are two important viruses for children with lower respiratory tract infections (LRTI). We aimed to assay the correlation between viral load and clinical characteristics of HBoV and HMPV with LRTI in Changsha, China. METHODS Nasopharyngeal aspirates (NPAs) from children with LRTI were collected. Real-time PCR was used to screen HBoV and HMPV. Analyses were performed using SPSS 16.0 software. RESULTS Pneumonia was the most frequent diagnosis. There was no significant difference between HBoV- and HMPV-positive patients in age (P = .506) or hospitalization duration (P = .280); 24.1% and 18.2% were positive for HBoV and HMPV. HBoV infections peaked in summer (32.2%), and HMPV infections peaked in winter (28.9%). The HBoV-positive patients had a shorter hospitalization duration than the HBoV-negative patients (P = .021), and the HMPV-positive patients had a higher prevalence of fever than the HMPV-negative patients (P = .002). The HBoV viral load was significantly higher among patients aged

Background/Aims: Metal stent insertion is a common palliative treatment for distal malignant biliary obstruction (MBO) but whether placement across the sphincter of Oddi (SO) causes more complications or shorter survival is in question. The aim of this study was to compare the clinical outcomes of percutaneous uncovered self-expandable metal stent placement above and across the SO in patients with distal MBO. Patients and Methods: We retrospectively studied 59 patients who underwent uncovered metal stent placement for distal MBO between January 2012 and March 2016. Stents were placed above the SO for 22 subjects (group A) and across the SO for 37 subjects (group B). Early cholangitis, stent occlusion, and overall survival time were compared between the two groups. Results: Clinical success was 90.9 and 86.5% for groups A and B, respectively. Early cholangitis occurred in 2 patients (9.1%) in group A and in 6 patients (16.2%) in group B (P = 0.645). Median stent patency and median survival time was 105 and 140 days for group A, 120 and 160 days for group B, respectively. The stent occlusion (31.8% in group A and 21.6% in group B, P = 0.454) and the cumulative stent patency times (P = 0.886) did not differ between the two groups. There was no significant difference in cumulative patient survival between the two groups (P = 0.810). Conclusion: Uncovered metal stent placement across the SO did not significantly affect early cholangitis, stent patency, or patient survival.

Objectives: Congenital renal arteriovenous malformations (rAVMs) represent rare vascular diseases. The heterogeneous vascular architecture of each rAVM determines the endovascular treatment techniques employed. We reported our experience with the endovascular treatment of a series of rAVMs. Materials: This retrospective study consisted of 12 patients with 12 rAVMs who underwent renal arterial embolization (RAE) in our hospital. Embolic materials, including particles, liquid embolic agents (n-butyl 2-cyanoacrylate, Onyx, and ethanol), and coils, were selectively used based on the decisions of interventional radiologists. Technical success was defined as the complete occlusion of the feeding arteries and nidus on postprocedure renal arteriography. Clinical success was defined as the resolution of hematuria or the disappearance of rAVM-relevant symptoms. Results: The median follow-up period was 13.5 months (range: 4-72). The technical success based on 12 procedures in 12 patients was 83.3% (10 of 12). In the 2 procedures that technically failed, the existence of multiple fine feeding arteries arising from the proximal portion of different segmental renal arteries explains the incomplete embolization. One of the 2 patients achieved clinical success without additional RAE. The other patient had recurrent hematuria 25 months after initial treatment, which was successfully managed conservatively with hemostatic agents. Thus, the clinical success was 91.7% (11 of 12). Conclusions: Renal artery embolization with the selective use of various embolic materials is an effective treatment for patients with rAVMs. The existence of multiple fine feeding vessels arising from the proximal portion of different segmental renal arteries is likely to affect the technical success of treatment.

AIMS: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system. Increasing evidence indicates that NMOSD is a Th2‐ and Th17‐dominant disease. IL‐25, IL‐31, and IL‐33 are three newly found Th2‐related cytokines, and their roles in the pathogenesis of NMOSD have not been studied. This study aimed to measure the serum levels of IL‐25, IL‐31, and IL‐33 in patients with NMOSD and evaluate their clinical implications. METHODS: Serum was collected from patients with NMOSD (n = 48) and healthy controls (HC, n = 28). Serum level measurements of IL‐25, IL‐31, IL‐33, IL‐17A, and IL‐6 were performed using enzyme‐linked immunoassay (ELISA) method. RESULTS: The serum levels of IL‐25, IL‐31, and IL‐33 were significantly higher in patients with NMOSD as compared to HC. The serum level of IL‐31 was significantly correlated with IL‐17A (r = 0.382,P = 0.009) in patients with NMOSD; the latter is a critical cytokine in the pathogenesis of NMOSD. The serum level of IL‐33 was higher in patients with characteristic brain lesions than patients without (307 pg/mL vs 166 pg/mL, P = 0.028). Furthermore, the serum level of IL‐33 in the acute phase of the disease was positively correlated with annualized relapse rate (r = 0.364, P = 0.04). CONCLUSION: We found higher serum levels of IL‐25, IL‐31, and IL‐33 in patient with NMOSD as compared to healthy controls. The serum level of IL‐33 during acute phase was associated with more past attacks in patients with NMOSD.

Oculomotor nerve palsy (ONP) may result from Posterior communicating artery (Pcom) aneurysms. Endovascular treatment of ruptured Pcom aneurysms generally is a safe procedure, but the effect of this therapy on ONP is incompletely elucidated. This retrospective study evaluates outcomes of ONP after endovascular treatment for ruptured Pcom aneurysm and with the intention to clarify predictors of recovery. From May 2010 to October 2015, 210 patients with Pcom aneurysms underwent endovascular treatment at our institution. Among them, 34 patients with ruptured aneurysms and either complete or incomplete ONP were identified. The outcomes and predictors of ONP recovery were analyzed. At the last available clinical follow-up, ONP resolution was complete in 21 (61.8%) patients and incomplete in 8 (23.5%) patients. The mean resolution time after embolization was 24.5 days. Five patients showed no signs of ONP recovery. In no case was an initial incomplete ONP observed to worsen. There was a statistically insignificant trend toward complete recovery among patients with initial incomplete ONP (OR = 4.17; 95% CI, 0.75–23.18; P = 0.103). Endovascular treatment appears to be an effective treatment modality for ruptured Pcom aneurysm and related ONP. The initial incomplete ONP might encourage complete ONP recovery after endovascular treatment.

Aberrant activation of beta-catenin/TCF signaling is one of the hallmarks of colon cancer. It is of great interest to study the mechanism for the regulation of beta-catenin/TCF signaling. In this study, it was found that LRP1B was down-regulated in colon cancer tissues and inhibited the growth, migration and metastasis of colon cancer cells. The molecular mechanism study revealed that LRP1B interacted with DVL2, inhibited the interaction between DVL2 and Axin, and negatively regulated beta-catenin/TCF signaling. Taken together, our study demonstrated the suppressive roles of LRP1B in the progression of colon cancer, implicating that restoring the function of LRP1B would be a promising strategy for the treatment of colon cancer.

Chemical hepatotoxicity, especially alcoholic liver injury (ALI), commonly occurs in young and middle-aged people who drink heavily. ALI is extremely harmful and can induce severe disease states, such as hepatitis, liver fibrosis, cirrhosis, or liver cancer, which are similar to CClThis study sought to elucidate the mechanisms underlying SCDL-mediated hepatoprotection.We first used in silico target prediction and computational simulation methods to identify putative lignan-binding targets relative to the hepatoprotective effect. A gene microarray analysis was performed to identify differently expressed genes that might have significance in the disease pathological process. We then used histological analyses in a mice hepatotoxicity model to test the effectiveness of SCDLs in vivo, and a hepatocellular toxicity model to analyze the candidate-compound-mediated hepatoprotection and expression states of the key targets in vitro.The in silico analysis results indicated that endothelin receptor B (ETBR/EDNRB) is likely a significant node during the liver pathological change process and a promising key target for the SCDL compound schisantherin D on the hepatoprotective effect; experimental studies showed that schisantherin D alleviated the EtOH- and ET-1-induced HL-7702 cell (belongs to liver parenchymal cell lines) injury ratio, decreased the expression of ETBR, and inhibited ECMs and ET-1 secretion in LX-2 cells (one form of hepatic stellate cells). SCDLs ameliorated EtOH- and CClThe findings indicated that SCDLs prevent hepatotoxicity via their anti-fibrotic, anti-oxidant, and anti-apoptosis properties. ETBR may be the key factor in promoting chemical hepatotoxicity.

The rational allocation of resources is crucial to suppress the outbreak of epidemics. Here, we propose an epidemic spreading model in which resources are used simultaneously to prevent and treat disease. Based on the model, we study the impacts of different resource allocation strategies on epidemic spreading. First, we analytically obtain the epidemic threshold of disease using the recurrent dynamical message passing method. Then, we simulate the spreading of epidemics on the Erdős-Renyi (ER) network and the scale-free network and investigate the infection density of disease as a function of the disease infection rate. We find hysteresis loops in the phase transition of the infection density on both types of networks. Intriguingly, when different resource allocation schemes are adopted, the phase transition on the ER network is always a first-order phase transition, while the phase transition on the scale-free network transforms from a hybrid phase transition to a first-order phase transition. Particularly, through extensive numerical simulations, we find that there is an optimal resource allocation scheme, which can best suppress epidemic spreading. In addition, we find that the degree heterogeneity of the network promotes the spreading of disease. Finally, by comparing theoretical and numerical results on a real-world network, we find that our method can accurately predict the spreading of disease on the real-world network.

Nowadays, early oral feeding after gastrectomy has been gradually accepted and applied in the clinical practice, but there is still no specific uniform feeding regimen available which works best for patients in different regions with different races and eating habits. Aiming to establish an early oral feeding schedule suitable for local Chinese patients after gastric surgery, from May 2014 to May 2018, 87 gastric cancer patients undergoing various types of gastric resections were enrolled in an early feeding protocol and their clinical course was reviewed retrospectively. A stepwise, local patient-specific, early oral feeding schedule was proposed, implemented within an early recovery after surgery (ERAS) protocol and accessed in terms of its safety and tolerability. The primary surgical outcomes included: a median (interquartile range; IQR) postoperative hospital stay of 6 (3) days; 67 (77%) patients were well tolerant of this schedule from postoperative day (POD) 1 to POD 4; 20 (23%) patients had mild I/II grade complications (Clavien-Dindo classification); 3 (3%) patients had IIIB complications, zero cases of hospital mortality. Compared to similar studies in the past, our early oral feeding program is also safe and beneficial, and it can shorten the postoperative hospital stay without causing any increase in postoperative complications. In summary, our work herein reported the establishment of a detailed early oral feeding schedule embedded within an ERAS protocol which was found to be suitable for local Chinese patients after gastric surgery. Accordingly, this early oral feeding schedule is worth further research and promotion.

Cervical cancer is one of the most common cancers threatening women's health, and the persistent infection of high-risk human papillomavirus (HPV) is closely related to the pathogenesis of cervical cancer and many other cancers. The carcinogenesis is a complex process from precancerous lesion to cancer, which provides an excellent window for clinical prevention, diagnosis, and treatment. However, despite the various preventions and treatments such as HPV screening, prophylactic HPV vaccines, surgery, radiotherapy, and chemotherapy, the disease burden remains heavy worldwide. Currently, three types of prophylactic vaccines, quadrivalent HPV vaccine, bivalent HPV vaccine, and a new nonavalent HPV vaccine, are commercially available. Although these vaccines are effective in protecting against 90% of HPV infection, they provide limited benefits to eliminate pre-existing infections. Therefore, new progress has been made in the development of therapeutic vaccines. Therapeutic vaccines differ from prophylactic vaccines in that they aim to stimulate cell-mediated immunity and kill the infected cells rather than neutralizing antibodies. This review aims at systematically covering the progress, current status and future prospects of various vaccines in development for the prevention and treatment of HPV-associated lesions and cancers and laying foundations for the development of the new original vaccine.

The purpose of this study was to find out the activity and molecular mechanism of NF-kB subunits in cervical cancer which in turn were used as a molecular marker in diagnosing cancer progression.Different cervical cancer biopsies were obtained from patients after obtaining proper written consent and approval, which were subjected to immunohistochemistry. Performed were Western blot analysis and electrophoretic mobility shift assays.Immunohistochemical analysis of low-grade, high-grade and squamous cell carcinoma (SCC) (stage IIIA, IIIB and IV) showed low to high nuclear expression of p52/RelB compared with p50/RelA, whereas in normal cells, c-Rel was expressed in the cytosol. p52/RelB expression was further validated by Western blot analysis. The binding ability of NF-κB to p52/RelB was increased during the progression of cervical cancer. All cervical carcinoma biopsies showed increased expression of p50/RelA and p52/RelB, but the p52/RelB NF-κB protein complex showed elevated nuclear expression and binding ability, indicating a pathway other than the classical pathway. The non-canonical NF-κB pathway also played an important role in cervical cancer progression by activating the p52/RelB NF-κB complex.This study provides a new approach for diagnosing, and establishing an appropriate treatment against cervical cancer progression.

Cervical cancer is a serious threat to women's health and is the third most common malignancy in women worldwide. Recent studies indicate that the long non-coding RNA CCAT1 plays a role in the malignant behavior of many tumors. However, the role of CCAT1 in cervical cancer is still unknown. Our aim is to evaluate the expression and investigate the regulatory role and potential mechanism of CCAT1 in cervical cancer. CCAT1 expression was measured by qRT-PCR. In addition, CCK-8 assays, colony formation assays, qRT-PCR assays, Transwell assays and xenograft experiments were performed to determine the role of CCAT1 in the proliferation and invasion in cervical cancer cells. The expression of CCAT1 in the cervical cancer tissues was higher than in the adjacent normal tissues. Overexpressing CCAT1 promoted cervical cancer cell proliferation, colony formation, and invasion in vitro. Elevated CCAT1 suppressed miR-181a expression, which was accompanied by an increased expression of MMP14 and HB-EGF. In contrast, knocking down CCAT1 resulted in increased expression of miR-181a, along with decreased expression of MMP14 and HB-EGF. Thus, CCAT1 is a key oncogenic lncRNA associated with cervical cancer and plays a role in promoting cervical cancer cell proliferation and invasion by regulating the miR-181a-5p/MMP14 axis.

Despite the overall success of using R-CHOP for the care for non-Hodgkin’s lymphoma patients, it is clear that the disease is quite complex and new insight is needed to further stratify the patient for a better personized treatment. In current study, based on previous studies from animal model, new panels combining well-established cytokine (BAFF) and autoantibodies (anti-SSA/Ro) with newly identified cytokine (IL14) and autoantibodies (TSA) were used to evaluate the association between B cell growth factor and Sjögren’s related autoantibodies in NHL patients. The result clearly indicates that there was a unique difference between BAFF and IL14 in association with autoantibodies. While serum BAFF was negatively associated with the presence of both traditional anti-SSA/Ro and novel TSA antibodies in GI lymphoma patient, IL14 was positively associated with the presence of both traditional anti-SSA/Ro and novel TSA antibodies in non-GI lymphoma patient. Long-term follow-ups on these patients and evaluation of their response to the R-CHOP treatment and recurrence rate will be very interesting. Our result provides a solid evidence to support using novel diagnostic panel to better stratify the NHL patients.

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well-defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty-seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real-time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged < 1 year (P = 0.003), children without fever and wheezing (P = 0.015 and P = 0.000), days of illness < 14 days (P = 0.002), children with bronchiolitis (P = 0.012) and children with RSV single infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co-infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89: 589-597, 2017. (C) 2016 Wiley Periodicals, Inc.

To investigate the prevalence, anatomy and distribution of the hepatic falciform artery (HFA) and Sappey’s superior artery (SSA) using C-arm CT hepatic arteriography (C-arm CTHA). From January 2011 to December 2012, 220 patients who underwent C-arm CTHA during initial transarterial treatment for hepatocellular carcinoma were included in this retrospective study. The HFAs and SSAs prevalence and origin were evaluated using axial images of C-arm CTHA. A 5-point scale for HFAs and a 4-point scale for SSAs were used to designate the radiologically conspicuous arteries. The prevalences of the total HFAs and SSAs were 95 % (n=209) and 22 % (n=49), while those of radiologically conspicuous HFAs and SSAs were 62 % (n=137) and 10 % (n=22), respectively. Thirty HFAs (22 % of radiologically conspicuous HFAs and 14 % of the total study population) were distributed in the subcutaneous layer of the anterior abdominal wall, while the majority of SSAs ran through the superior part of the falciform ligament in the left-anterior direction and anastomosed with left inferior phrenic artery. Our study using C-arm CTHA revealed that the prevalence of the HFA is higher than the existing knowledge and proved the existence of the SSA radiologically for the first time. • Prevalence of hepatic falciform artery is 95 %, higher than previously known. • 22 % of conspicious hepatic falciform arteries distributed in subcutaneous tissue around umbilicus. • The existence of Sappey’s superior artery was proved with a radiological method.

Transarterial embolization (TAE) appears to be a safe and effective treatment for patients with intractable epistaxis, despite different etiologies or angiography findings. Idiopathic epistaxis is prone to present with negative angiographic findings.To retrospectively evaluate the safety and effectiveness of TAE for intractable epistaxis, and focus on the factors of etiology and angiographic findings.From March 2008 to December 2014, the data of 43 patients with intractable bleeding undergoing TAE were reviewed. The outcomes of interventional therapy were assessed according to different etiology (malignant or benign disease) and angiographic finding (positive or negative angiogram).Positive angiographic findings were found in 11 of 12 cases with malignant diseases and 22 of 31 cases with benign diseases, respectively (p = 0.237). Among the 10 cases with negative angiographic findings, the negative angiography rate of idiopathic epistaxis was higher than that of epistaxis with definite etiology (p = 0.003). Bleeding was controlled successfully in all of the 43 patients after embolization. During the mean follow-up period of 24.0 ± 16.7 months, five patients relapsed. No significant difference was found in recurrence rates between malignant and benign diseases or between positive and negative angiography (p = 0.241, p = 0.704, respectively).