Transurethral water vapour thermal therapy for benign prostatic hyperplasia under local anaesthesia alone: initial experience in Chinese patients.

INTRODUCTION: This study evaluated the perioperative and early postoperative outcomes of transurethral water vapour thermal therapy (WVTT) under local anaesthesia alone for benign prostatic enlargement in Chinese patients. METHODS: This retrospective review of transurethral WVTT for benign prostatic enlargement focused on 50 Chinese patients who exhibited clinical indications (acute retention of urine or symptomatic lower urinary tract symptoms due to benign prostatic enlargement) for surgical treatment between June 2020 and December 2021 in Hong Kong. Exclusion criteria included active urinary tract problems and urological malignancies. Follow-up was conducted at 3 months postoperatively. RESULTS: The median patient age was 71.5 years. The mean preoperative prostatic volume was 56.7 mL. The mean operation time was 25.1 minutes. All procedures were performed under local anaesthesia alone. The mean pain scores for transrectal ultrasound probe insertion, transperineal local anaesthesia injection, and transurethral WVTT were 2, 5, and 4, respectively. Forty-nine patients (98%) were discharged on the same day with a urethral catheter. Forty-eight patients (96%) successfully completed a trial without catheter within 3 weeks postoperatively. Five patients (10%) had unplanned hospital admission within 30 days postoperatively due to surgical complications (Clavien-Dindo grade 1). CONCLUSION: Transurethral WVTT, an advanced surgical treatment for benign prostatic enlargement, is a safe procedure that relieves lower urinary tract symptoms with minimal hospital stay. It can be performed in an office-based setting under local anaesthesia, maximising utilisation of the surgical theatre.

Preclinical evaluation of the VEGF/Ang2 bispecific nanobody BI 836880 in nasopharyngeal carcinoma models.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic to parts of Asia and overexpression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α are common in NPC. Anti-vascular agents have known clinical activity in patients with recurrent/ metastatic NPC and in this study, we investigated the anti-tumor effect of BI 836880, a humanized bispecific nanobody against VEGF and angiopoietin-2 (Ang2), in preclinical models of EBV-positive and EBV-negative NPC. The efficacy of BI 836880 was also compared with bevacizumab, a recombinant humanized monoclonal antibody against VEGF. We found that BI 836880 could exert growth-inhibitory effect on endothelial cells (HUVEC-C) and the EBV-negative NPC cell line (HK1), but to a lesser extent in the EBV-positive NPC cell lines, C17C and C666-1. In patients-derived xenograft (PDX) models of NPC - Xeno-2117 and Xeno-666, BI 836880 could suppress tumor growth and Ki67, as well as induce tumor necrosis and reduce microvessel density. Moreover, treatment with BI 836880 increased the level of macrophage infiltration in both PDX tumor models of NPC, suggesting that BI 836880 may exert immunomodulatory effect on the NPC immune microenvironment. When compared with bevacizumab, BI 836880 appeared to show at least comparable activity as bevacizumab in terms of its anti-proliferative and anti-angiogenic effects. This study showed that BI 836880 has anti-proliferative, anti-angiogenic and possibly immunomodulatory effect in clinical models of NPC, therefore the dual targeting of VEGF and Ang2 signaling in NPC should be further investigated.

The relationship between famine exposure in early life and left atrial enlargement in adulthood.

BACKGROUND: Increased left atrium diameter (LAD) is associated with an elevated risk of cardiovascular diseases. The relationship between nutrition status and left atrial enlargement (LAE) is still unclear. The present study aimed to investigate the association of famine exposure in early life with LAE in adulthood. METHODS: Participants were divided into non-exposed, fetal, early, middle and late childhood exposed groups according to birth data. LAE was defined when LAD was ≥3.9 cm in women and ≥4.1 cm in men, or ≥2.3 cm m-2 by a sex-independent cut-off normalised for body surface area. Multivariate logistic regression was performed to calculate the odds ratio (OR) and confidence interval (CI) between famine exposure and LAE. RESULTS: In total, 2522 [905 male, mean (SD) age 59.1 (3.65) years] subjects were enrolled, including 392 (15.5%) LAE subjects. The prevalence of LAE in non-exposed, fetal, early, middle and late childhood exposed groups was 55 (10.8%), 38 (11.2%), 88 (18.1%), 102 (16.7%) and 109 (19.0%), respectively. Compared to the non-exposed group, the ORs for LAE were in fetal (OR = 0.956, 95% CI = 0.605-1.500, P = 0.847), late (OR = 1.748, 95% CI = 1.208-2.555, P = 0.003), middle (OR = 1.647, 95% CI = 1.140-2.403, P = 0.008) and early (OR = 1.630, 95% CI = 1.116-2.399, P = 0.012) childhood exposed groups after adjusting potential cofounders. When stratified by gender, smoking, body mass index, hypertension and diabetes, we found that the effect of famine exposure on LAE was only modified by diabetes (Pinteraction  = 0.007). CONCLUSIONS: Famine exposure during childhood stage might increase the risk of LAE in adults, and this effect interacts with diabetes.

The St. George's Respiratory Questionnaire in Pulmonary Sarcoidosis.

RATIONALE: The Saint George's Respiratory Questionnaire (SGRQ) is a frequently used tool to assess health status in pulmonary disease patients. However, its performance characteristics in sarcoidosis patients are not well characterized. METHODS: Data from a clinical trial of 138 symptomatic adults with sarcoidosis were used to examine the performance characteristics of SGRQ. Data were available at both baseline and week 24. Other assessments included FVC, FEV1, ATS dyspnea score, Borg's CR 10 dyspnea score, 6-min walk distance (6MWD), and Short Form-36 Physical Component Summary (SF-36 PCS) score. RESULTS: Baseline SGRQ was 46.8, indicating impaired health status. At baseline, SGRQ total score correlated significantly with % predicted FVC, FEV1, ATS dyspnea score, Borg's CR 10 dyspnea score, 6MWD, and SF-36 PCS (r = - 0.37, - 0.32, 0.57, 0.40, - 0.55, and - 0.80, respectively, p < 0.001). Change from baseline in SGRQ score also statistically significantly correlated with change from baseline in these parameters at week 24: r = - 0.25, - 0.20, 0.30, 0.22, - 0.20, - 0.45, respectively (p < 0.05). CONCLUSIONS: The SGRQ correlated with other outcome measures in sarcoidosis initially and with treatment. Improvement in FVC % predicted correlated with improvement in SGRQ. These data suggest the SGRQ may function as a reliable endpoint in clinical sarcoidosis trials.

Theoretical Tools to Analyze Anorectal Mechanophysiological Data Generated by the Fecobionics Device.

A mechanical approach is needed for understanding anorectal function and defecation. Fecal continence is achieved by several interacting mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, motility, and psychological factors. The balance is easily disturbed, resulting in symptoms such as fecal incontinence and constipation. Novel technologies have been developed in recent years for studying anorectal function. Especially, the Fecobionics device, a simulated feces, has gained attention recently. This facilitates new analysis of anorectal mechanical function. In this study, a theoretical model is developed to analyze anorectal mechanophysiological data generated by the Fecobionics device. Theoretical approaches can enhance future interdisciplinary research for unraveling defecatory function, sensory-motor disorders, and symptoms. This is a step in the direction of personalized treatment for gastrointestinal disorders based on optimized subtyping of anorectal disorders.

Outcomes of transperineal and transrectal ultrasound-guided prostate biopsy.

OBJECTIVE: To compare the clinical outcomes and pathological findings of transperineal ultrasound-guided prostate biopsy (TPUSPB) and transrectal ultrasound-guided prostate biopsy (TRUSPB) in a secondary referral hospital. METHODS: This was a retrospective study of 100 TPUSPBs and 100 TRUSPBs performed in our centre. Pre-biopsy patient parameters (eg, patient age, clinical staging, serum prostate-specific antigen [PSA] level, prostate size, and PSA density), as well as pathological results and 30-day complication and readmission rates, were retrieved from the patients' medical records and compared between the two groups. RESULTS: One hundred TPUSPBs performed from January 2018 to May 2018 and 100 TRUSPBs performed from January 2016 to April 2016 were included for analysis. Mean age did not significantly differ between the groups. The TPUSPB group had a higher mean PSA level, smaller prostate size, and higher PSA density, compared with the TRUSPB group. The overall prostate cancer detection rate was similar between the TPUSPB and TRUSPB groups (35% vs 25%, P=0.123). There were no significant differences between the groups in prostate cancer detection rates after stratification according to PSA density and clinical staging. With respect to complications, no patients developed fever in the TPUSPB group, while 4% of patients in the TRUSPB group had fever and required at least 1-week admission for intravenous antibiotic administration. CONCLUSION: For prostate biopsy, TPUSPB is safer, with no infection complications, and has similar prostate cancer detection rate compared with TRUSPB.

Tandem thiotepa with autologous hematopoietic cell rescue in patients with recurrent, refractory, or poor prognosis solid tumor malignancies.

BACKGROUND: The purpose of this study was to determine the feasibility and tolerability of tandem courses of high-dose thiotepa with autologous hematopoietic cell rescue (AHCR) in patients with recurrent, refractory solid tumors who were ineligible for a single course of high-dose therapy due to greater than minimal residual disease. Patients with decreased hearing or poor renal function were eligible. PROCEDURE: Thiotepa was administered intravenously at a dose of 200 mg/m2 /day (6.67 mg/kg/day) daily for 3 days followed by AHCR. A second course of thiotepa was given 4 weeks later provided blood counts recovered sufficiently without evidence of tumor progression. RESULTS: Fifty-eight patients received 96 courses. Thirty-eight (65%) patients received two courses of therapy. Twenty-seven courses (28%) were administered completely in the outpatient setting. A toxic mortality rate of 3.4% was observed. Five of 26 patients with medulloblastoma were alive at a median of 35 months, whereas 21 patients died at a median of 11.7 months. Four of five patients with central nervous system germ cell tumors (CNS GCT) were alive 68-103 months following AHCR. CONCLUSIONS: Two cycles of high-dose thiotepa with AHCR were well tolerated even in these heavily pretreated patients. This therapy may provide prolonged survival in patients with recurrent malignant brain tumors, particularly medulloblastoma and CNS GCT.

Microwave enhanced advanced oxidation treatment of dairy manure.

The microwave enhanced advanced oxidation process (MW-AOP) was used to treat dairy manure in a continuous-flow 915 MHz microwave wastewater treatment system. The treatment efficiency increased with an increase in temperature, as well as hydrogen peroxide dosage. The settling property was also improved in all treated sets, regardless of temperature applied. The system operated at temperatures >100 °C had a much higher soluble chemical oxygen demand than at temperatures <100 °C. The highest soluble carbonaceous compounds, orthophosphate and ammonia were obtained at 110 °C and 0.6%H2O2 per % of total solids content. The process should be operated at higher temperatures and higher hydrogen peroxide dosages for maximizing solids disintegration, nutrient release and energy efficiency. An energy fingerprint correlating the cumulative energy consumption and temperature rise was developed. The results demonstrated that the custom designed MW-AOP system is suitable for the effective treatment of dairy manure. The system can readily be scaled up and integrated into a dairy farm manure treatment and resource recovery system.

TSC1/2 mutations define a molecular subset of HCC with aggressive behaviour and treatment implication.

OBJECTIVE: We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis. DESIGN: We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models. RESULTS: We identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of TSC1 and TSC2 genes in the HCC samples. The spectrum of TSC1/2 mutations likely disrupts the endogenous gene functions in suppressing the downstream mTOR activity through different mechanisms and leads to more aggressive tumour behaviour. Mutational disruption of TSC1 and TSC2 was also observed in HCC cell lines and our PDTX models. TSC-mutant cells exhibited reduced colony-forming ability on rapamycin treatment. With the use of biologically relevant TSC2-mutant PDTXs, we demonstrated the therapeutic benefits of the hypersensitivity towards rapamycin treatment. CONCLUSIONS: Taken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent TSC1/2 mutations in HBV-associated HCCs. They define a molecular subset of HCC having genetic aberrations in mTOR signalling, with potential significance of effective specific drug therapy.

Men's knowledge of their own fertility: a population-based survey examining the awareness of factors that are associated with male infertility.

STUDY QUESTION: How knowledgeable are men about the medical, environmental and psychological factors that are associated with male infertility? SUMMARY ANSWER: Men, across most demographic groups, have limited knowledge of the various factors that are associated with male infertility. WHAT IS KNOWN ALREADY: Few surveys have focused on men's knowledge of their own fertility. Studies of both men and women have found that men are comparatively less knowledgeable about issues of fertility and reproductive health. STUDY DESIGN, SIZE, DURATION: A regionally representative sample of Canadian men completed a web-based survey of male fertility and reproductive health, over a 2-month period in 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men, aged 18-50 years, were recruited for the study. There were 701 male participants, with a mean age of 34.1 years. Each participant was asked to identify factors associated with male infertility; fertility knowledge was assessed through two open-ended questions and a comprehensive list of risk factors and attendant health issues. MAIN RESULTS AND THE ROLE OF CHANCE: Men were only able to identify 51% of the risk factors and 45% of the health issues associated with male infertility. Men were most aware of the modifiable risk factors for infertility (e.g. sexually transmitted infections, smoking cigarettes), relative to their knowledge of fixed risk factors (e.g. delayed puberty, size of testicles) and the attendant health issues (e.g. cardiovascular disease, diabetes). The overall level of fertility knowledge did not vary by most demographic characteristics (e.g. age, education, employment, income), though men from ethnic minority groups displayed moderately greater awareness. Additionally, younger men, those with lower incomes and those who had no desire to have future biological children were more likely to identify themselves as unaware of associations with infertility in the open-ended questions. Self-reported knowledge was significantly associated with higher overall knowledge scores. More than half of the sample expressed an interest in obtaining information about male fertility and reproductive health, with the majority of these men indicating that medical professionals and online sources were their preferred methods for receiving information. LIMITATIONS, REASONS FOR CAUTION: Participants were self-selected and required to have Internet access in order to participate. This may affect the generalizability of results. WIDER IMPLICATIONS OF THE FINDINGS: Previous studies of fertility knowledge have either omitted men from their samples or when men have been included, they were asked about general fertility or women's fertility. This is the first large-scale survey that focuses solely on men's knowledge of male fertility. Insight into the areas where men's knowledge may be lacking can inform strategies for disseminating fertility-related information and improving men's fertility awareness. Public health initiatives should tailor campaigns to educate men about the lesser known associations with male infertility, particularly those that are most prevalent and preventable through lifestyle modification. STUDY FUNDING/COMPETING INTERESTS: The study was funded by a grant from CIHR TE1-138296. No competing interests.

Multicenter phase II study of the AKT inhibitor MK-2206 in recurrent or metastatic nasopharyngeal carcinoma from patients in the mayo phase II consortium and the cancer therapeutics research group (MC1079).

BACKGROUND: This study investigated the activity of MK-2206, an AKT inhibitor, in metastatic or recurrent nasopharyngeal carcinoma (NPC). METHOD: Oral MK-2206 at a dose of 200 mg was administered on days 1, 8, 15 and 22 of a 28-day cycle until progression. Plasma EBV DNA clearance during the first month of treatment was measured, and archived tumors were analyzed for the expression of AKT and PIK3CA mutation and PIK3CA amplification. The dual primary endpoint was objective response rate and 6-month progression-free survival (PFS) rate. RESULTS: 21 patients were enrolled and one patient achieved a partial response (5 %) and 11 had stable disease (52 %), with a median PFS of 3.5 months (95 % confidence interval, CI: 0.9-7.3). The 6-month PFS rate was 43 % (95 % CI: 22-66 %) and the median OS was 10 months (95 % CI: 5.9 months-not reached). Seven patients (33 %) experienced grade 3 toxicities which could be related to MK-2206. Macular-papular rash was the most common (n = 6), followed by hyperglycemia (n = 2) and fatigue (n = 1). In the 12 tumor samples analyzed, PIK3CA amplification was detected in one patient's primary NPC, who had SD lasting over 12 months. Patients with decreasing EBV DNA values over time were more likely to be alive and progression-free for at least 6 months than those without a decrease (p = 0.001). CONCLUSION: The study was terminated due to the limited activity observed in this heavily pre-treated group of patients. Further studies are needed to elucidate the optimal way of selecting patients for AKT inhibitors.

PubMed-supported clinical term weighting approach for improving inter-patient similarity measure in diagnosis prediction.

BACKGROUND: Similarity-based retrieval of Electronic Health Records (EHRs) from large clinical information systems provides physicians the evidence support in making diagnoses or referring examinations for the suspected cases. Clinical Terms in EHRs represent high-level conceptual information and the similarity measure established based on these terms reflects the chance of inter-patient disease co-occurrence. The assumption that clinical terms are equally relevant to a disease is unrealistic, reducing the prediction accuracy. Here we propose a term weighting approach supported by PubMed search engine to address this issue. METHODS: We collected and studied 112 abdominal computed tomography imaging examination reports from four hospitals in Hong Kong. Clinical terms, which are the image findings related to hepatocellular carcinoma (HCC), were extracted from the reports. Through two systematic PubMed search methods, the generic and specific term weightings were established by estimating the conditional probabilities of clinical terms given HCC. Each report was characterized by an ontological feature vector and there were totally 6216 vector pairs. We optimized the modified direction cosine (mDC) with respect to a regularization constant embedded into the feature vector. Equal, generic and specific term weighting approaches were applied to measure the similarity of each pair and their performances for predicting inter-patient co-occurrence of HCC diagnoses were compared by using Receiver Operating Characteristics (ROC) analysis. RESULTS: The Areas under the curves (AUROCs) of similarity scores based on equal, generic and specific term weighting approaches were 0.735, 0.728 and 0.743 respectively (p < 0.01). In comparison with equal term weighting, the performance was significantly improved by specific term weighting (p < 0.01) but not by generic term weighting. The clinical terms "Dysplastic nodule", "nodule of liver" and "equal density (isodense) lesion" were found the top three image findings associated with HCC in PubMed. CONCLUSIONS: Our findings suggest that the optimized similarity measure with specific term weighting to EHRs can improve significantly the accuracy for predicting the inter-patient co-occurrence of diagnosis when compared with equal and generic term weighting approaches.

Characteristics and outcomes of patients with percutaneous coronary intervention for unprotected left main coronary artery disease: a Hong Kong experience.

OBJECTIVE: To evaluate the intermediate-term outcomes of patients with unprotected left main coronary artery stenosis who were treated with percutaneous coronary intervention in Hong Kong. DESIGN: Historical cohort. SETTING: A regional hospital in Hong Kong. PATIENTS: Patients with unprotected left main coronary artery disease undergoing stenting with bare-metal stents or drug-eluting stents between January 2008 and September 2011. MAIN OUTCOME MEASURES: Incidence of restenosis and major adverse cardiac and cerebrovascular events including cardiac death, non-fatal myocardial infarction, stroke, and target lesion revascularisation. RESULTS: Of the 111 patients included in the study, 86 received drug-eluting stents and 25 received bare-metal stents. Procedural success was achieved in 98.2% of cases. Angiographic follow-up was available in 83.8% of cases and restenosis rate was significantly lower with drug-eluting stents than with bare-metal stents (14.0% vs 40.0%; P=0.004). After a mean clinical follow-up of 26.1 (standard deviation, 12.6) months, the incidences of cardiac death (5.8% vs 16.0%; P=0.191) and non-fatal myocardial infarction (3.5% vs 8.0%; P=0.262) were similar between drug-eluting stents and bare-metal stents. However, the risks of target lesion revascularisation (9.3% vs 32.0%; P=0.001) and major adverse cardiac and cerebrovascular events (19.8% vs 44.0%; P=0.004) were significantly lower with drug-eluting stents than with bare-metal stents. CONCLUSIONS: Performing percutaneous coronary intervention for unprotected left main coronary artery disease was safe and feasible in selected patients with high procedural success rate. The incidence of major adverse cardiac and cerebrovascular events in patients receiving drug-eluting stents remains low after intermediate-term follow-up. Compared with bare-metal stents, drug-eluting stents were associated with a lower need for repeating revascularisation without increasing the risk of death or myocardial infarction in patients with unprotected left main coronary artery disease.

Scrotal antegradesclerotherapy demonstrates anatomical variations on venous drainage in paediatric, adolescent and young adult varicoceles.

AIM OF THE STUDY: Anatomical variations on venous drainage in varicoceles are under-reported. We report our experience in scrotal antegrade sclerotherapy (SAS) for adolescent varicoceles. METHODS: Since 2011, 15 consecutive boys with left varicoceles were recruited. Under general anaesthesia, a 5-mm transverse incision was made at scrotal neck, testicular vein was cannulated at pampiniform plexus with venogram performed. Foam sclerosant by mixing sodium tetradecyl sulphate (STS), Lipiodol(®) and air was slowly injected under fluoroscopy. Postoperatively the patients were followed-up for varicocele grading, testicular size, and complications. MAIN RESULTS: Median age at operation was 14 (10-19) years. 80 % had grade three varicoceles, 33.3 % had smaller left testis before operation. Intra-operative venogram showed three different anatomical variations. Group I: eleven patients (73.3 %) had single distinct internal spermatic vein; Group II: two patients demonstrated duplication of internal spermatic vein draining into left renal vein; Group III: two patients had pampiniform plexus draining to iliac and/or paraspinal veins. SAS was performed in Group I and II patients. Sclerosant volume injected ranged from 1.5 to 4.5 ml. In Group III patients, surgical ligation of testicular veins was performed rather than SAS to avoid uncontrolled systemic sclerosant spillage. Mean length of stay was 1.13 day. One patient with scrotal haematoma and one other with minor wound dehiscence were managed conservatively. Mean follow-up period was 10.9 (1-22) months. Thirteen patients (86.7 %) achieved varicocele grading ≤ 1. There was no postoperative testicular atrophy, hydrocele and epididymo-orchitis. CONCLUSION: Scrotal antegrade sclerotherapy using STS foam is a safe and effective treatment for adolescent varicoceles. Anatomical variations on venous drainage in varicoceles are common.

Operational strategy for nitrogen removal from centrate in a two-stage partial nitrification--anammox process.

This paper presents the operational strategy for nitrogen removal in a two-stage, partial nitrification (PN) process coupled with anaerobic ammonium oxidation (Anammox) process. The process was used to remove ammonium from centrate obtained from a full-scale, wastewater treatment plant in British Columbia, Canada. The PN, which was carried out in a sequencing batch reactor (SBR), successfully converted approximately 49.5 +/- 1.0% of ammonium to nitrite. The operation of SBR under higher dissolved oxygen in combination with slow feeding resulted in significant reduced HRT without nitrate accumulation. Partially nitrified centrate was further treated in Anammox reactors, where the mixture of ammonium and nitrite was converted mainly to nitrogen gas. Anammox treatment was carried out in two different types of Anammox reactors: a moving bed hybrid reactor and an up-flow fixed-bed biofilm reactor. The hybrid Anammox reactor removed an average of 55.8% of NH4-N, versus the 48.3% NH4-N removed in the up-flow fixed-bed reactor. Nitrite removal in the hybrid and up-flow fixed-bed Anammox reactors averaged 80.8% and 62.5%, respectively. This study also illustrated that in both Anammox reactors, better ammonium removal was achieved when the nitrite to ammonium ratio is between 1.35 and 1.45. As such, alkalinity was found to neither control nor limit the Anammox reaction.

Tongue-Coating Microbial and Metabolic Characteristics in Halitosis.

Halitosis is a common oral condition, which leads to social embarrassment and affects quality of life. Cumulative evidence has suggested the association of tongue-coating microbiome with the development of intraoral halitosis. The dynamic variations of tongue-coating microbiota and metabolites in halitosis have not been fully elucidated. Therefore, the present study aimed to determine the tongue-coating microbial and metabolic characteristics in halitosis subjects without other oral diseases using metagenomics and metabolomics analysis. The participants underwent oral examination, halitosis assessment, and tongue-coating sample collection for the microbiome and metabolome analysis. It was found that the microbiota richness and diversity were significantly elevated in the halitosis group. Furthermore, species from Actinomyces, Prevotella, Veillonella, and Solobacterium were significantly more abundant in the halitosis group. However, the Rothia and Streptococcus species exhibited opposite tendencies. Eleven Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched in the halitosis tongue coatings, including cysteine and methionine metabolism. Functional genes related to sulfur, indole, skatole, and cadaverine metabolic processes (such as serA, metH, metK and dsrAB) were identified to be more abundant in the halitosis samples. The metabolome analysis revealed that indole-3-acetic, ornithine, and L-tryptophan were significantly elevated in the halitosis samples. Furthermore, it was observed that the values of volatile sulfur compounds and indole-3-acetic abundances were positively correlated. The multiomics analysis identified the metagenomic and metabolomic characteristics to differentiate halitosis from healthy individuals using the least absolute shrinkage and selection operator logistic regression and random forest classifier. A total of 19 species and 39 metabolites were identified as features in halitosis patients, which included indole-3-acetic acid, Bacillus altitudinis, Candidatus Saccharibacteria, and Actinomyces species. In conclusion, an evident shift in microbiome and metabolome characteristics was observed in the halitosis tongue coating, which may have a potential etiological significance and provide novel insights into the mechanism for halitosis.

Laparoscopic Heller's cardiomyotomy achieved lesser recurrent dysphagia with better quality of life when compared with endoscopic balloon dilatation for treatment of achalasia.

Achalasia is a rare primary motility disorder of esophagus; treatments include endoscopic balloon dilatation (EBD) and laparoscopic Heller's cardiomyotomy (LC). This study compared EBD versus LC for treatment of achalasia with focus on quality of life (QoL) and prevalence of post-treatment gastroesophageal reflux disease. This was a retrospective cohort study of all patients diagnosed with achalasia older than 16 treated with either EBD or LC from January 1998 to April 2008. Patients' demographic data, comorbidities, postintervention GERD symptoms, QoL, recurrence of dysphagia, reintervention rate, hospital stay, and time to resumption of diet were collected. Sixty-eight patients were recruited into the study (EBD n= 50; LC n= 18). A significant improvement in QoL was found in patients undergoing LC (0.917 vs. 0.807, P= 0.006). A higher proportion of patients treated with EBD developed post-treatment gastroesophageal reflux symptoms (60.5% vs. 43.8%) when compared with LC, although statistically insignificant (P= 0.34). Patients treated with balloon dilatation had a greater percentage of recurrence of dysphagia (55.1% vs. 26.7%; P= 0.235) and need of reintervention (42.1% vs. 9.1%; P= 0.045). However, these patients had a shorter median hospital stay (1d [range 0-4]) and earlier resumption of diet (0d [range 0-3]). Although EBD is associated with a quicker perioperative recovery, LC accomplished a better QoL, lower incidence of recurrence of dysphagia, and need of reintervention after treatment for achalasia.

Development of the hybrid Sleeping Beauty: baculovirus vector for sustained gene expression and cancer therapy.

Antiangiogenesis is an appealing anticancer approach but requires continued presence of the antiangiogenic agents, which can be remedied by gene therapy. Baculovirus is an emerging gene delivery vector but only mediates transient expression (<7 days); thus, this study primarily aimed to develop a hybrid baculovirus for sustained antiangiogenic gene expression and cancer therapy. We first constructed plasmids featuring adeno-associated virus inverted terminal repeats (AAV ITRs), oriP/Epstein-Barr virus-expressed nuclear antigen 1 (EBNA1) or Sleeping Beauty (SB) transposon and compared their efficacies in terms of persistent expression. In human embryonic kidney (HEK293) cells, AAV ITR failed to prolong the expression while oriP/EBNA1 moderately extended the expression to 35 days. In contrast, the SB system led to stable expression beyond 77 days even without antibiotic selection. Given this finding, we constructed a hybrid SB baculovirus expressing the SB transposase and harboring the transgene cassette flanked by inverted repeat/direct-repeat (IR/DR) elements recognizable by SB. The hybrid SB baculovirus efficiently transduced mammalian cells and mediated an expression duration longer than that by conventional baculoviruses, thanks to the transgene persistence and integration. The SB baculovirus (Bac-SB-T2hEA/w) expressing the antiangiogenic fusion protein comprising endostatin and angiostatin (hEA) also enabled prolonged hEA expression. With sustained hEA expression, Bac-SB-T2hEA/w repressed the angiogenesis in vivo, hindered the growth of two different tumors (prostate tumor allografts and human ovarian tumor xenografts) in mice and extended the life span of animals. These data altogether implicated the potential of the hybrid SB-baculovirus vector for prolonged hEA expression and for the treatment of multiple types of angiogenesis-dependent tumors.