The trends of pediatric duodenal ulcer and predictors of recurrence.

BACKGROUND: Duodenal ulcer (DU) causes various symptoms in children. The prevalence of Helicobacter pylori (Hp)-associated DU has been reducing in some regions, yet the updated trend in Taiwan is unknown. Risk factors of DU recurrence have not been comprehensively investigated in children. METHODS: This retrospective study included children diagnosed with DU to evaluate the demographics, symptoms, diagnostics, treatment, and outcomes. Specific populations (infant, surgery required) were sorted for subgroup analysis. Predictors of DU recurrence was analyzed in patients who received endoscopic follow-ups. RESULTS: A total of 488 children were included. Most patients were male (72.5%), school-aged (11.3 ± 4.8 years old), and with varied underlying diseases in one-fifth. The annual incidences were around 3-5%, with a declining trend of case numbers and the Hp-positive proportion. Hp infection, concurrent gastric ulcer, perforation, and mortality were noted in 32.7%, 16%, 1.6%, and 1% of patients. Patients with or without Hp infection showed different clinical features but similar outcomes. The characteristics of subpopulations were depicted respectively. Male sex, lower Hb level, and perforation were independent risk factors associated with recurrence. CONCLUSIONS: Hp-positive DU seems to wane. Patients with male sex, lower Hb level, or perforation at diagnosis carried a higher risk of recurrence, which may warrant active surveillance and endoscopic follow-up.

Factors Determining Testicular Torsion and Consequent Orchiectomy in Pediatric Patients Presenting With Scrotal Pain.

OBJECTIVE: Factors associated with testicular torsion (TT) and consequent orchiectomy in patients presenting to pediatric emergency departments (PEDs) with scrotal pain (SP) are not well described. We report the factors predicting TT and consequent orchiectomy in children with SP. METHODS: The data on patients (aged ≤18 years) who presented with SP to PEDs at 4 branches of the Chang Gung Hospital through 10 years were analyzed. RESULTS: In all, 256 pediatric patients presented with SP. Their mean age was 11.60 ± 4.61 years and 72.7% (n = 186) were aged 10 to 18 years. The pain was left-sided in 54.7% (n = 140) and the interval between SP onset and PED arrival was 22.45 ± 31.27 hours. Overall, 84 (32.8%) patients needed surgery and 72 (28.1%) had TT. Of the patients with TT, 28 (38.9%) patients needed an orchiectomy. After analysis, TT and consequent orchiectomy were associated with a longer interval between SP onset and PED arrival, absent of testicular ultrasonic blood flow, interval between SP onset and surgery of more than 24 hours, and a high degree of TT. None of them experienced recurrent SP symptoms or TT again. CONCLUSIONS: The rate of TT in patients presenting to PEDs with an SP was 28.1%, and 38.9% of the patients with TT needed an orchiectomy. Early diagnosis and intervention helped to prevent subsequent orchiectomy in pediatric patients with TT.

MiR-424/TGIF2-Mediated Pro-Fibrogenic Responses in Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) has been recognized as a potentially malignant disorder and is characterized by inflammation and the deposition of collagen. Among various regulators of fibrogenesis, microRNAs (miR) have received great attention but the detailed mechanisms underlying the miR-mediated modulations remain largely unknown. Here, we showed that miR-424 was aberrantly overexpressed in OSF tissues, and then we assessed its functional role in the maintenance of myofibroblast characteristics. Our results demonstrated that the suppression of miR-424 markedly reduced various myofibroblast activities (such as collagen contractility and migration ability) and downregulated the expression of fibrosis markers. Moreover, we showed that miR-424 exerted this pro-fibrosis property via direct binding to TGIF2, an endogenous repressor of the TGF-ß signaling. In addition, our findings indicated that overexpression of miR-424 activated the TGF-ß/Smad pathway, leading to enhanced myofibroblast activities. Altogether, our data revealed how miR-424 contributed to myofibroblast transdifferentiation, and targeting the miR-424/TGIF2 axis may be a viable direction for achieving satisfactory results from OSF treatment.

Curbing COVID-19 progression and mortality with traditional Chinese medicine among hospitalized patients with COVID-19: A propensity score-matched analysis.

BACKGROUND: Viral- and host-targeted traditional Chinese medicine (TCM) formulae NRICM101 and NRICM102 were administered to hospitalized patients with COVID-19 during the mid-2021 outbreak in Taiwan. We report the outcomes by measuring the risks of intubation or admission to intensive care unit (ICU) for patients requiring no oxygen support, and death for those requiring oxygen therapy. METHODS: This multicenter retrospective study retrieved data of 840 patients admitted to 9 hospitals between May 1 and July 26, 2021. After propensity score matching, 302 patients (151 received NRICM101 and 151 did not) and 246 patients (123 received NRICM102 and 123 did not) were included in the analysis to assess relative risks. RESULTS: During the 30-day observation period, no endpoint occurred in the patients receiving NRICM101 plus usual care while 14 (9.27%) in the group receiving only usual care were intubated or admitted to ICU. The numbers of deceased patients were 7 (5.69%) in the group receiving NRICM102 plus usual care and 27 (21.95%) in the usual care group. No patients receiving NRICM101 transitioned to a more severe status; NRICM102 users were 74.07% less likely to die than non-users (relative risk= 25.93%, 95% confidence interval 11.73%-57.29%). CONCLUSION: NRICM101 and NRICM102 were significantly associated with a lower risk of intubation/ICU admission or death among patients with mild-to-severe COVID-19. This study provides real-world evidence of adopting broad-spectrum oral therapeutics and shortening the gap between outbreak and effective response. It offers a new vision in our preparation for future pandemics.

Depletion of miR-155 hinders the myofibroblast activities and reactive oxygen species generation in oral submucous fibrosis.

BACKGROUND/PURPOSE: Emerging evidence suggests the significance of microRNA-155 (miR-155) in fibrogenesis and oxidative stress accumulation, but its function in oral submucous fibrosis (OSF) has not been investigated. In this study, we assessed the expression of miR-155 and its effects on the maintenance of myofibroblast activation. METHODS: qRT-PCR was conducted to assess the expression of miR-155 in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF samples. Collagen gel contraction, migration, and invasion capabilities were examined in fBMFs. DCFDA ROS assay was used to examine ROS generation. A luciferase reporter assay was carried out to verify the relationship between miR-155 and its potential target RPTOR. RESULTS: We showed that the expression of miR-155 was aberrantly upregulated in OSF specimens and fBMFs. Inhibition of miR-155 ameliorated various myofibroblast activities, including collagen gel contraction, migration, and invasion abilities as well as ROS production. Results from the luciferase reporter assay demonstrated that miR-155 directly interacted with its target RPTOR. CONCLUSION: Taken together, these findings indicate that miR-155 is implicated in the pathogenesis of oxidative stress-associated OSF, possibly through the regulation of RPTOR.

Silencing periostin inhibits myofibroblast transdifferentiation of fibrotic buccal mucosal fibroblasts.

BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF) a well-recognized oral premalignant disorder. Several studies have demonstrated that periostin, a matricellular protein, is involved in the development and pathogenesis of fibrosis diseases. Nevertheless, the contribution of periostin in OSF remains to be uncovered. The purpose of the study was to illustrate the functional role of periostin involved in OSF pathogenesis. METHODS: RNA-sequencing was employed to screen for differentially expressed genes in normal and OSF tissues. Validation of the upregulation of periostin in OSF specimens and fibrotic buccal mucosal fibroblasts (fBMFs) was conducted by qRT-PCR. The correlation of the gene expression of periostin and various fibrosis markers was analyzed. In addition, the functional role of periostin in myofibroblast features was tested using collagen gel contraction and transwell migration assays. RESULTS: We observed overexpression of periostin in OSF specimens using RNA-sequencing and confirmed its upregulation in OSF tissues and patient-derived fBMFs. Besides, there was a positive relationship between the expression of periostin and several fibrosis-associated markers, including ACTA2 (α-smooth muscle actin; α-SMA), COL1A1 (type 1 collagen α1 chain), TGFB1 (TGF-ß1), and FN1 (fibronectin). Furthermore, we examined the effect of silencing periostin on the maintenance of myofibroblast characteristics and showed that knockdown of periostin suppressed the expression of α-SMA. Also, inhibition of periostin markedly downregulated the myofibroblast activities (collagen gel contraction and migration capacities). CONCLUSION: Our results indicate the aberrant expression of periostin in OSF tissues and myofibroblasts. Moreover, the expression of periostin is positively associated with fibrosis markers, and repression of periostin may be a promising direction to alleviate the progression of OSF.

Association of oral health-related quality of life and Alzheimer disease: A systematic review.

STATEMENT OF PROBLEM: Oral health-related quality of life (OHRQoL) is a subjective measure that assesses a person's perception of oral health. Patients with Alzheimer disease (AD) suffer from impaired cognitive function and a compromised ability to perform activities of daily living. Further exploration is needed to clarify whether OHRQoL is negatively impacted by cognitive degeneration and oral health conditions among patients with AD. PURPOSE: The purpose of this systematic review was to increase understanding of OHRQoL among patients with AD and explore factors that may affect OHRQoL. MATERIAL AND METHODS: Searches were conducted in PubMed, the Cochrane Library database, Medline, EBSCO, ProQuest, and EMBASE until August 30, 2018, with no date restrictions. The initial search targeted quantitative observational studies published in English that included the keywords AD, oral, prosthesis, and OHRQoL. Data extraction was independently conducted by 2 reviewers. OHRQoL was investigated as the outcome. Cognitive status and oral health conditions were treated as exposures. Tools used to measure OHRQoL included the Geriatric Oral Health Assessment Index (GOHAI) and the Oral Health Impact Profile. The research adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Six studies were included. The sample sizes ranged from 30 to 226 participants, 5 studies used cross-sectional designs, and 1 was a nonrandomized controlled trial. Three studies reported higher OHRQoL scores among participants with AD than those among controls, but only 1 study showed a statistically significant difference. A statistical analysis was conducted with 4 studies that reported GOHAI scores, and no significant differences were found in GOHAI scores between participants with AD and controls (standard mean difference: 0.09; 95% confidence interval: -0.66 to 0.85). All studies that explored factors affecting OHRQoL showed different associations between cognitive impairment, oral health conditions, and OHRQoL. One study showed that cognitive impairment was negatively associated with OHRQoL. Three studies found oral health conditions (including periodontitis, gingival bleeding, probing depth >4 mm, and number of natural teeth) impaired the OHRQoL of participants with AD. Three studies reported that prosthetic type and quality positively affected OHRQoL among participants with AD. CONCLUSIONS: OHRQoL may not fully represent actual oral health problems of patients with AD. Clinical dentists should evaluate oral problems in this population, preferably by using both subjective and objective examinations, including oral and dental conditions. This will ensure oral problems among patients with AD can be detected early and timely treatment provided.

miR-1246 as a therapeutic target in oral submucosa fibrosis pathogenesis.

BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF) is a precancerous condition of oral cancer with a complex etiology. Our previous work has demonstrated that non-coding RNA miR-1246 contributes to the cancer stemness of oral cancer. In the current study, we sought to investigate the effect of the inhibition of miR-1246 on the oral fibrogenesis. METHODS: The expression levels of miR-1246 in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were examined by qRT-PCR. Collagen gel contraction and migration assays were conducted to evaluate the myofibroblast activities. The relationship between miR-1246 and type I collagen was assessed and the protein expression of type I collagen was determined by Western blot. RESULTS: MiR-1246 expression was upregulated in both OSF specimen and fBMFs compared to the normal counterparts. Inhibition of miR-1246 successfully suppressed the myofibroblast activities, including collagen gel contractility and migration capacity. Moreover, the expression of miR-1246 was positively correlated with type I collagen and the expression of type I collagen was abrogated by repression of miR-1246. CONCLUSION: MiR-1246 is not only critical to the maintenance of oral stemness but also important to the activation of myofibroblasts. Our results showed that miR-1246 is positively associated with the type I collagen, which may be a downstream effector of miR-1246 and responsible for the fibrosis effect on fBMFs.

Efficacy and Safety of a Low-Level Light Therapy for Androgenetic Alopecia: A 24-Week, Randomized, Double-Blind, Self-Comparison, Sham Device-Controlled Trial.

BACKGROUND: Previous studies have reported the benefits of low-level/light laser therapy (LLLT) for the promotion of hair regrowth. However, the effectiveness of LLLT for the treatment of androgenetic alopecia (AGA) is still a topic of debate. OBJECTIVE: To investigate the efficacy and safety of LLLT on hair regrowth in patients with AGA. METHODS: This 24-week, randomized, double-blind, self-comparison, sham device-controlled trial enrolled 100 patients with AGA. All participants were randomly assigned to receive the investigational LLLT on one side of the head and sham light treatment on the contralateral side, 3 times weekly for 30 minutes each, over a 24-week period. Global scalp photography, phototrichogram assessment, the investigator's global assessment (IGA) of hair regrowth, and the subject's assessment of the treatment satisfaction were used for evaluation. RESULTS: After 24 weeks of treatment, the LLLT-treated scalp exhibited significantly greater hair coverage than the sham light-treated side (14.2% vs. 11.8%, p < .001). A significantly greater improvement from baseline in hair thickness, hair count, hair coverage, and IGA were also observed in the LLLT-treated side than in the sham light-treated side at the 12- and 24-week visits. No serious adverse events were observed. CONCLUSION: The use of LLLT might be an effective, safe, well-tolerated treatment for AGA.

The status of Her2 amplification and Kras mutations in mucinous ovarian carcinoma.

Jayson GC et al. remarked in Lancet that nearly 100% of mucinous ovarian cancer cases have Kras mutation as well as a high frequency of Her2 amplification. Using the Abbott PathVysion Her2 DNA Probe Kit and Kras mutant-enriched PCR Kits (FemtoPath®), 21 samples of primary ovarian mucinous cystadenocarcinomas from Taiwanese patients were examined to determine the status of Her2 amplification and Kras mutations. Our results showed the Her2 amplification rates were 33.33%, while the Kras mutation rates were 61.90%. We present here our results in order to enlighten the readership that the ~100% Kras mutant frequency and the high Her2 amplification rate reported by Jayson et al. may be too exaggerated to be applicable into all populations. Additionally, we report another 2 novel Kras mutations (A11V, V14I).

Downregulation of miR-1 enhances tumorigenicity and invasiveness in oral squamous cell carcinomas.

BACKGROUND/PURPOSE: Cumulative evidence suggest that microRNAs (miRNAs) function as biosignatures of oral squamous cell carcinomas (OSCC). However, the functional roles of miR-1 as well as its downstream targets in the regulation of tumorigenicity in OSCC remain unclear. METHODS: miRNAs RT-PCR analysis was performed to identify miR-1 as a putative candidate on mediating invasiveness of OSCC cells. Consequently, we elucidated the tumorigenicity of OSCC cells with miR-1 downregulation or overexpression, respectively. Finally, miR-1 on OSCC tumor tissues was examined. RESULTS: miR-1 levels were significantly downregulated in the malignant OSCC cells. Overexpression of miR-1 significantly reduced migration/invasiveness of OSCC cells. In addition, overexpression of miR-1 decreased cancer stem cells properties. Conversely, downregulation of miR-1 promotes migration and invasiveness in OSCC cells. We have shown that miR-1 is able to target Slug, suppressing their expression. Clinically, lower miR-1 expression was found in patients with advanced nodal metastasis OSCC. CONCLUSION: miR-1 as novel biosignatures in OSCC lymph node metastatic patients, supporting the development of novel strategies for OSCC treatment.

Experience of single-incision laparoscopy in children.

CONTEXT: Laparoscopic surgery is commonly used for the treatment of many pediatric surgical diseases at our department. Single-incision laparoscopic surgery (SILS) is well-known for its cosmetic benefit. We, hereby, present our experience of SILS and evaluate its efficacy. MATERIALS AND METHODS: From July 2012 to June 2014, 78 patients aged less than 18 years who underwent SILS were retrospectively evaluated. There were 44 males and 34 females, with a mean age of 10.3 years. The procedures included appendectomy (n = 64), reduction of intussusception (n = 8), removal of an intestinal foreign body (n = 3), and Meckel's diverticulectomy (n = 3). We compared the patients who underwent SILS with those who underwent conventional laparoscopic surgery (CLS), regarding these procedures. The parameters for analysis included the patient's demographic data, surgical indication, complications, operative time, and length of hospital stay. CONCLUSION: SILS is comparable to CLS regarding two major procedures, namely, appendectomy and reduction of intussusception. There were no significant differences between the two groups regarding the patients' demographic data, complications, and length of hospital stay. According to our experience of SILS, it could be a feasible and safe procedure for the treatment of various pediatric surgical diseases. However, large prospective randomized studies are needed to identify the differences between SIL and CLS.

Elevated Lin28B expression is correlated with lymph node metastasis in oral squamous cell carcinomas.

BACKGROUND: Lymph node (LN) metastasis is the most common cause of oral squamous cell carcinoma (OSCC)-related death. Searching the detailed molecular mechanisms involved LN metastasis in OSCC is still an open question. METHODS: Paired tissue samples from tumor (T) and adjacent non-cancerous matched tissues (NCMT) parts, as well as LN metastatic lesions in patient with OSCC tissues were subjected to quantitative real-time PCR analysis for the expression levels of Lin28B. Arecoline, a major areca nut alkaloid, was to explore whether expression of Lin28B could be changed dose dependent in oral epithelial cells. Control and Lin28B-knockdown arecoline-stimulated oral epithelial cells were subjected to migration/invasion/anchorage-independent growth assay. RESULTS: Compared with NCMT samples from the same OSCC patient, the expression of Lin28B was increased in all of the tumor samples. A similar upregulation of Lin28B was also observed in LN metastatic when compared with local tumors. Arecoline treatment dose dependently induced Lin28B expression in SG and FaDu cells. Lentiviral-mediated silencing Lin28B expression significantly attenuated arecoline-induced oncogenicity including proliferation, migration, invasiveness, and anchorage-independent growth in SG and FaDu cells. CONCLUSIONS: Lin28B may be a useful biomarker and novel molecular target for LN metastasis OSCC patients' treatment.

Resveratrol suppresses TPA-induced matrix metalloproteinase-9 expression through the inhibition of MAPK pathways in oral cancer cells.

BACKGROUND: Naturally occurring agents, such as resveratrol, have been determined to benefit health. Numerous studies have demonstrated that resveratrol has antioxidative, cardioprotective, and neuroprotective properties. However, the effect of resveratrol exerts on the metastasis of oral cancer cells remains unclear. In this study, we investigated the effect the anti-invasive activity of resveratrol on a human oral cancer cell line (SCC-9) in vitro and the underlying mechanisms. METHODS: Cell viability was examined by MTT assay, whereas cell motility was measured by migration and wound-healing assays. Zymography, reverse-transcriptase polymerase chain reaction (PCR), and promoter assays confirmed the inhibitory effects of resveratrol on matrix metalloproteinase-9 (MMP-9) expression in oral cancer cells. RESULTS: We established that various concentrations (0-100 µM) of resveratrol inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced migration capacities of SCC-9 cells and caused no cytotoxic effects. Zymography and Western blot analyses suggested that resveratrol inhibited TPA-induced MMP-9 gelatinolytic activity and protein expression. In addition, the results indicated that resveratrol inhibited the phosphorylation of c-Jun N-terminal kinase (JNK)1/2 and extracellular-signal-regulated kinase (ERK)1/2 involved in downregulating protein expression and the transcription of MMP-9. CONCLUSION: In summary, resveratrol inhibited MMP-9 expression and oral cancer cell metastasis by downregulating JNK1/2 and ERK1/2 signals pathways and, thus, exerts beneficial effects in chemoprevention.

A putative novel protein, DEPDC1B, is overexpressed in oral cancer patients, and enhanced anchorage-independent growth in oral cancer cells that is mediated by Rac1 and ERK.

BACKGROUND: The DEP domain is a globular domain containing approximately 90 amino acids, which was first discovered in 3 proteins: Drosophila disheveled, Caenorhabditis elegans EGL-10, and mammalian Pleckstrin; hence the term, DEP. DEPDC1B is categorized as a potential Rho GTPase-activating protein. The function of the DEP domain in signal transduction pathways is not fully understood. The DEPDC1B protein exhibits the characteristic features of a signaling protein, and contains 2 conserved domains (DEP and RhoGAP) that are involved in Rho GTPase signaling. Small GTPases, such as Rac, CDC42, and Rho, regulate a multitude of cell events, including cell motility, growth, differentiation, cytoskeletal reorganization and cell cycle progression. RESULTS: In this study, we found that it was a guanine nucleotide exchange factor and induced both cell migration in a cultured embryonic fibroblast cell line and cell invasion in cancer cell lines; moreover, it was observed to promote anchorage-independent growth in oral cancer cells. We also demonstrated that DEPDC1B plays a role in regulating Rac1 translocated onto cell membranes, suggesting that DEPDC1B exerts a biological function by regulating Rac1. We examined oral cancer tissue; 6 out of 7 oral cancer tissue test samples overexpressed DEPDC1B proteins, compared with normal adjacent tissue. CONCLUSIONS: DEPDC1B was a guanine nucleotide exchange factor and induced both cell migration in a cultured embryonic fibroblast cell line and cell invasion in cancer cell lines; moreover, it was observed to promote anchorage-independent growth in oral cancer cells. We also demonstrated that DEPDC1B exerts a biological function by regulating Rac1. We found that oral cancer samples overexpressed DEPDC1B proteins, compared with normal adjacent tissue. Suggest that DEPDC1B plays a role in the development of oral cancer. We revealed that proliferation was linked to a novel DEPDC1B-Rac1-ERK1/2 signaling axis in oral cancer cell lines.

Regression analysis of multivariate current status data with dependent censoring: application to ankylosing spondylitis data.

Multivariate current-status failure time data consist of several possibly related event times of interest, in which the status of each event is determined at a single examination time. If the examination time is intrinsically related to the event times, the examination is referred to as dependent censoring and needs to be taken into account. Such data often occur in clinical studies and animal carcinogenicity experiments. To accommodate for possible dependent censoring, this paper proposes a joint frailty model for event times and dependent censoring time. We develop a likelihood approach using Gaussian quadrature techniques for obtaining maximum likelihood estimates. We conduct extensive simulation studies for investigating finite-sample properties of the proposed method. We illustrate the proposed method with an analysis of patients with ankylosing spondylitis, where the examination time may be dependent on the event times of interest.

Weight reduction effect of Puerh tea in male patients with metabolic syndrome.

Puerh tea has been proposed to promote weight loss and favorably modify glucose, insulin and blood lipids. This study tested the effect of daily Puerh tea consumption for 3 months on weight and body mass index (BMI), and select metabolic parameters. The effect of daily Puerh tea intake on weight, BMI and changes in glucose, HbA1c and lipids was evaluated in patients with metabolic syndrome. The patients (N = 70) were randomized into two groups: those taking Puerh tea extract capsule (333 mg Puerh tea extract) three times a day and those taking a placebo tea for 3 months. There was a decrease in body weight of 1.3 kg in the Puerh tea group (p = 0.077) versus 0.23 kg in the placebo arm (p = 0.186). There was also a slight decrease in BMI 0.47 kg/m(2) in the Puerh tea group (p = 0.076) versus 0.09 kg/m(2) in the placebo arm (p = 0.185), suggesting a trend of weight change, but without statistical significance. Subgroup analysis of the male patients demonstrated statistically significant improvements in body weight reduction (p = 0.004) and BMI (p = 0.004). However, the change in other metabolic parameters (cholesterol or triglyceride) or HbA1c was not statistically significant. Intake of Puerh tea for 3 months was associated with a slight reduction in body weight and BMI, especially in the male patients. Therefore, daily Puerh tea consumption may be an alternative choice to modify body weight.