Endoscopic ultrasound-guided lauromacrogol injection for treatment of colorectal cavernous hemangioma: Two case reports.

BACKGROUND: Colorectal cavernous hemangioma is a rare vascular malformation resulting in recurrent lower gastrointestinal hemorrhage, and can be misinterpreted as colitis. Surgical resection is currently the mainstay of treatment, with an emphasis on sphincter preservation. CASE SUMMARY: We present details of two young patients with a history of persistent hematochezia diagnosed with colorectal cavernous hemangioma by endoscopic ultrasound (EUS). Cavernous hemangioma was relieved by several EUS-guided lauromacrogol injections and the patients achieved favorable clinical prognosis. CONCLUSION: Multiple sequential EUS-guided injections of lauromacrogol is a safe, effective, cost-efficient, and minimally invasive alternative for colorectal cavernous hemangioma.

2023: A year of accomplishments for the 13 Science Citation Index Expanded- and Emerging Sources Citation Index-indexed Baishideng journals.

In 2023, Baishideng Publishing Group (Baishideng) routinely published 47 open-access journals, including 46 English-language journals and 1 Chinese-language journal. Our successes were accomplished through the collective dedicated efforts of Baishideng staffs, Editorial Board Members, and Peer Reviewers. Among these 47 Baishideng journals, 7 are included in the Science Citation Index Expanded (SCIE) and 6 in the Emerging Sources Citation Index (ESCI). With the support of Baishideng authors, company staffs, Editorial Board Members, and Peer Reviewers, the publication work of 2023 is about to be successfully completed. This editorial summarizes the 2023 activities and accomplishments of the 13 SCIE- and ESCI-indexed Baishideng journals, outlines the Baishideng publishing policy changes and additions made this year, and highlights the unique advantages of Baishideng journals.

Characteristics and Risk Factors of Functional Dyspepsia Fulfilling the Rome IV Criteria Overlapping With Gastroesophageal Reflux Disease, Irritable Bowel Syndrome, and Functional Constipation in South China.

Background/Aims: Functional dyspepsia (FD) overlapping with other gastrointestinal disorders are quite common. The characteristics of FD overlap in Chinese population with latest Rome IV criteria were unclear. This large-scale outpatient-based study assessed the characteristics of FD overlap in South China. Methods: Consecutive FD patients visited the Gastroenterology Clinic at 2 tertiary medical centers in Hangzhou, China who fulfilled the Rome IV criteria were enrolled. Complete questionnaires related to the gastrointestinal symptoms (Rome IV criteria), Reflux Disease Questionnaire, anxiety and depression, quality of sleep and life, and demographic information were collected. Results: Among the total of 3281 FD patients, 50.69% overlapped with gastroesophageal reflux disease, 21.46% overlapped with irritable bowel syndrome, 6.03% overlapped with functional constipation. FD overlap had higher proportion of single/divorced/widowed rate, high education level, being employed, drinking, night shift, unhealthy dietary habit than FD only (P < 0.05). They had higher frequency of consultation and economic burden, as well as lower scores in quality of life (P < 0.001). Multivariate logistic regression showed that increasing age, female, low body mass index, history of gastroenteritis, anxiety, depression, and poor sleep quality were independent risk factors for FD overlap. Conclusions: FD overlap was quite common in China with high economic burden and poor quality of life, FD patients with history of gastroenteritis, anxiety, depression, and poor sleep quality were more likely to have overlap disorders. Awareness of the physical and psychosocial stressors in overlapping condition would help optimize the management of FD overlap in clinical practice.

Influence of Age and Gender on Nasal Airway Patency as Measured by Active Anterior Rhinomanometry and Acoustic Rhinometry.

In this study, we aimed to investigate the influences of age and gender on nasal airway patency, as measured by both active anterior rhinomanometry (AAR) and acoustic rhinometry (AR). The nasal airway patency of healthy subjects was evaluated using AAR and AR. In AAR, the subjects generated airflow actively through inspiration and expiration in repetitions of 10, while nasal patency was measured at an inspiratory and expiratory reference pressure of 75 Pa. In AR, we assessed the geometry of the nasal cavity through the analysis of sound waves reflected from the nasal cavities in order to measure both cross-sectional areas and nasal volumes. The subjects were divided by gender, with all males and females then grouped by ages of 20-39 years, 40-59 years and ≥60 years. There were 40 subjects in each group. The mean resistance measured by AAR and the cross-sectional areas and nasal volumes measured by AR were not different between the different age groups; however, the cross-sectional areas and nasal volumes were found to be lesser in females than in males. Our results showed that nasal airway patency was not affected by age, while females were shown to have wider nasal passages than males.

Improving ocular bioavailability of hydrophilic drugs through dynamic covalent complexation.

The clinical benefits of diquafosol tetrasodium (DQS), a hydrophilic P2Y2 receptor agonist for dry eye, have been hindered by a demanding dosing regimen. Nevertheless, it is challenging to achieve sustained release of DQS with conventional drug delivery vehicles which are mainly designed for hydrophobic small molecule drugs. To address this, we developed an affinity hydrogel for DQS by taking advantage of borate-mediated dynamic covalent complexation between DQS and hydroxypropyl guar. The resultant formulation (3% DQS Gel) was characterized by sustained release, low corneal permeation, and extended ocular retention, which were desirable attributes for ocular surface drug delivery. Both in vitro and in vivo studies had been carried out to verify the biocompatibility of 3% DQS Gel. Using corneal fluorescein staining, the Schirmer's test, PAS staining, quantitative PCR and immunohistological analyses as outcome measures, the superior therapeutic effects of 3% DQS Gel over PBS, the hydrogel vehicle and free DQS were demonstrated in a mouse dry eye model. Our DQS delivery strategy reported herein is readily applicable to other hydrophilic small molecule drugs with cis-diol moieties, thus providing a general solution to improve clinical outcomes of numerous diseases.

The analgesic effects of ß-elemene in rats with neuropathic pain by inhibition of spinal astrocytic ERK activation.

Neuropathic pain takes a heavy toll on individual well-being, while current therapy is far from desirable. Herein, we assessed the analgesic effect of ß-elemene, a chief component in the traditional Chinese medicine Curcuma wenyujin, and explored the underlying mechanisms at the level of spinal dorsal horn (SDH) under neuropathic pain. A spared nerve injury (SNI)-induced neuropathic pain model was established in rats. Intraperitoneal injection (i.p.) of ß-elemene was administered for 21 consecutive days. Mechanical allodynia was explored by von Frey filaments. The activation of the mitogen-activated protein kinase (MAPK) family (including ERK, p38, and JNK) in spinal neurons, astrocytes, and microglia was evaluated using immunostaining 29 days after SNI surgery. The expression of GFAP, Iba-1, p-ERK, p-JNK, and p-p38 within the SDH was measured using immunoblotting. The levels of proinflammatory cytokines (including TNF-α, IL-1ß, and IL-6) were measured with ELISA. The levels of oxidative stress indicators (including MDA, SOD, and GSH-PX) were detected using biochemical tests. Consecutive i.p. administration of ß-elemene relieved SNI-induced mechanical allodynia (with an EC50 of 16.40 mg/kg). SNI significantly increased the expression of p-ERK in spinal astrocytes but not microglia on day 29. ß-elemene reversed spinal astrocytic ERK activation and subsequent upregulation of proinflammatory cytokines in SNI rats, with no effect on the expression of p38 and JNK in spinal glia. ß-elemene also exerted antioxidative effects by increasing the levels of SOD and GSH-PX and decreasing the level of MDA. Our results suggest that SNI induces robust astrocytic ERK activation within the SDH in the late phase of neuropathic pain. ß-elemene exerts remarkable analgesic effects on neuropathic pain, possibly by inhibiting spinal astrocytic ERK activation and subsequent neuroinflammatory processes. Our findings suggest that ß-elemene might be a promising analgesic for the treatment of chronic pain.

Validation of the clinical applicability of the brief self-administered waterless empirical taste test during the era of COVID-19.

BACKGROUND: This study was performed to test the clinical applicability of a new taste test, the Brief Self-Administered Waterless Empirical Taste Test (B-WETT) in the era of COVID-19. METHODS: Sixty healthy volunteers and 60 patients experiencing gustatory dysfunction were enrolled. All subjects received both the Self-Administered WETT and the new B-WETT which are comprised of disposable plastic strips containing sucrose, citric acid, sodium chloride, caffeine, and monosodium glutamate tastants to evaluate taste function. The healthy volunteers were re-tested with the WETT and B-WETT after an inter-test interval of at least 7 days to measure retest reliability. RESULTS: The sum scores of five tastants of the first test were 25.7 for males and 29.5 for females in WETT, and 12.4 for males and 15.2 for females in B-WETT. There were significant differences in the sum scores between males and females whether in WETT or B-WETT. The sum scores strongly correlated between WETT and B-WETT, whether in healthy volunteers or in patients with gustatory dysfunction (r >0.7). There was also a strong correlation between the first and second tests of B-WETT for the sum scores. CONCLUSION: This study shows that B-WETT is a valid and reliable taste test, and is convenient for use in the era of COVID-19 to evaluate the taste function of patients.

Thyroid Disorders and Dementia Risk: A Nationwide Population-Based Case-Control Study.

BACKGROUND AND OBJECTIVES: Dementia has been gaining attention in aging societies and is estimated to affect 50 million adults globally in 2020, and 12% of the US population may develop a thyroid disorder in their lifetime. There have been limited studies investigating the correlation between thyroid disorder and dementia in the Asian population. METHODS: Our large nationwide population-based case-control study used the Taiwanese National Health Insurance Research Database. A total of 7,843 adults with newly diagnosed dementia without a history of dementia or neurodegenerative disease between 2006 and 2013 were identified and included in our study. In addition, 7,843 adults without dementia diagnosis before the index date were age and sex-matched as controls. Diagnosis of hyperthyroidism or hypothyroidism before the diagnosis of dementia or the same index date was identified. Results were obtained from logistic regression models and adjusted for sex, age, history of hypertension, diabetes, coronary artery disease, depression, hyperlipidemia, alcohol dependence syndrome, tinnitus, hearing loss, and radioactive iodine treatment. RESULTS: A total of 15,686 patients were included in the study. Both case and control groups were slightly predominantly female (4,066 [51.8%]). The mean (SD) age for those with dementia was 74.9 (11.3) years and for those without dementia was 74.5 (11.3) years. Among patients aged 65 years or older, a history of hypothyroidism was associated with an increased risk of being diagnosed with dementia (adjusted odds ratio [aOR] 1.81; 95% CI 1.14-2.87; p = 0.011), which was an association not present in patients older than 50 years but younger than 65 years. We found that this association was most significant among patients aged 65 years or older with a history of hypothyroidism who received hypothyroidism medication (aOR 3.17; 95% CI 1.04-9.69; p = 0.043). DISCUSSION: Our large-scale case-control study found that among people aged 65 years or older, those with a history of hypothyroidism were associated with an 81% increased risk of having dementia and among those, there was a more than 3-fold increased dementia risk with thyroid conditions that required thyroid hormone replacement treatment. Future well-controlled prospective longitudinal studies should be conducted to elucidate these potential mechanisms and relationships. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that among patients aged 65 years or older, a history of hypothyroidism was associated with an increased risk of being diagnosed with dementia.

Transoral Robotic Surgery for Early-T Stage Glottic Cancer Involving the Anterior Commissure-News and Update.

BACKGROUND: About 20% of all glottic carcinomas involve the anterior commissure (AC), and AC involvement was deemed to be a risk factor of local recurrence and poor prognosis. Transoral robotic surgery (TORS) has been developed for a panoramic view of the AC and en-bloc resection of the tumor by multidirectional dissection with endo-wristed instruments. With satisfactory preliminary results, we would like to update the data with a bigger cohort and present the news on using TORS for salvage treatment of recurrence from irradiation failure. METHODS: From July 2010 to December 2019, 22 patients with early T1 and 2 stage primary (n = 11) or recurrent (n = 11) glottic cancer with AC involvement received TORS without adjuvant therapy. TORS exposure was found to be better than TLM by conventional laryngoscopy in diagnostic biopsy. Seven of the 22 patients had recurrent cancer from irradiation failure. The perioperative factors that may be associated with survival were retrospectively analyzed, and the 5-year overall survival (OS)/disease-specific survival (DSS)/recurrence-free survival (RFS)/and organ preservation survival (OPS) rate were estimated by the Kaplan-Meier Method. Their voice and swallowing functions were evaluated by questionnaires of Voice Handicap Index-10 (VHI-10) and Functional Outcome Swallowing Scale (FOSS). RESULTS: All 22 TORSs were completed smoothly. After a mean follow-up of 49 ± 35.9 months, the Kaplan-Meier method estimated 5-year OS/DSS/RFS/OPS was 93.8%, 93.8%, 74.6%, and 86.3%, respectively. Our 11 patients with fresh cancer had 100% recurrence-free survival. Although the recurrent rate was higher in patients with history of RT, they could be rescued by further open laryngectomy without compromising the OS and DSS. Only one patient expired. The other 21 patients had satisfactory swallowing function with FOSS of 0.33 ± 0.66. Five patients depended on tracheostomy, but the rest 17 patients had serviceable voice with VHI-10 of 18.41 ± 11.29. CONCLUSIONS: TORS could be used in the primary or salvage management of glottic cancer with AC involvement while TORS was confirmed to have better exposure to TLM. The RFS was good for patients with primary cancer. In patients having irradiation failure, TORS could also be a minimally invasive transoral approach before trying open surgery to preserve the organ.

A topical fluorometholone nanoformulation fabricated under aqueous condition for the treatment of dry eye.

Fluorometholone (FMT) is a frequently prescribed drug for the alleviation of dry eye. However, due to low aqueous solubility, it has been routinely used as an ophthalmic suspension, which is characterized by low bioavailability, inconvenience of administration, and difficulty in delivering accurate dose. Furthermore, the opaque appearance of the ophthalmic suspension is not desirable for optical purpose. In the present study, a transparent FMT nanoformulation (FMT-CD NPs) was fabricated by the cyclodextrin (CD) nanoparticle technology without organic solvents. It was demonstrated that FMT was encapsulated in an amorphous form, which was associated with increased release rate and enhanced corneal penetration efficiency. The biocompatibility of FMT-CD NPs was confirmed by the Live/Dead assay, CCK-8 assay and the wound healing assay. Most importantly, FMT-CD NPs alleviated dry eye signs more efficiently than the commercial eye drop, with one-fifth the dosage of FMT in the latter. Collectively, our study provides a promising FMT formulation for improved management of dry eye while reducing drug related side effects.

Validation of the local applicability of the 'TIB' Olfactory Test Device in the era of COVID-19.

OBJECTIVE: To evaluate the validity and test-retest reliability of the novel 'TIB' Olfactory Test Device (TIB) and to determine its normative values. METHODS: The study stratified the study subjects into normosmic, hyposmic and anosmic groups according to their olfactory function. The olfactory function of the subjects was evaluated using both the traditional Chinese version of the University of Pennsylvania of Smell Identification Test (UPSIT-TC) and the TIB. The normosmic group was used to retest with the UPSIT-TC and TIB at an inter-test interval of at least 7 days. The cut-off scores of TIB among the three different groups were determined by receiver operating characteristic curve analysis. RESULTS: This study enrolled 180 subjects: 60 in each group. The mean scores of TIB were 44.1 for the normosmic group, 27.5 for the hyposmic group and 10.9 for the anosmic group. The TIB scores were significantly different across the three groups. There was a significant correlation between the first and second TIB tests (r = 0.506). The cut-off scores were 41 for normosmic subjects and 24 for hyposmic subjects. CONCLUSION: The validity and test-retest reliability results suggest that the TIB is an appropriate olfactory test for the Taiwanese population.

Predictive value of alarm symptoms in Rome IV irritable bowel syndrome: A multicenter cross-sectional study.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional bowel disease that shares features with many organic diseases and cannot be accurately diagnosed by symptom-based criteria. Alarm symptoms have long been applied in the clinical diagnosis of IBS. However, no study has explored the predictive value of alarm symptoms in suspected IBS patients based on the latest Rome IV criteria. AIM: To investigate the predictive value of alarm symptoms in suspected IBS patients based on the Rome IV criteria. METHODS: In this multicenter cross-sectional study, we collected data from 730 suspected IBS patients evaluated at 3 tertiary care centers from August 2018 to August 2019. Patients with IBS-like symptoms who completed colonoscopy during the study period were initially identified by investigators through medical records. Eligible patients completed questionnaires, underwent laboratory tests, and were assigned to the IBS or organic disease group according to colonoscopy findings and pathology results (if a biopsy was taken). Independent risk factors for organic disease were explored by logistic regression analysis, and the positive predictive value (PPV) and missed diagnosis rate were calculated. RESULTS: The incidence of alarm symptoms in suspected IBS patients was 75.34%. Anemia [odds ratio (OR) = 2.825, 95% confidence interval (CI): 1.273-6.267, P = 0.011], fecal occult blood [OR = 1.940 (95%CI: 1.041-3.613), P = 0.037], unintended weight loss (P = 0.009), female sex [OR = 0.560 (95%CI: 0.330-0.949), P = 0.031] and marital status (P = 0.030) were independently correlated with organic disease. The prevalence of organic disease was 10.41% in suspected IBS patients. The PPV of alarm symptoms for organic disease was highest for anemia (22.92%), fecal occult blood (19.35%) and unintended weight loss (16.48%), and it was 100% when these three factors were combined. The PPV and missed diagnosis rate for diagnosing IBS were 91.67% and 74.77% when all alarm symptoms were combined with Rome IV and 92.09% and 34.10% when only fecal occult blood, unintended weight loss and anemia were combined with Rome IV, respectively. CONCLUSION: Anemia, fecal occult blood and unintended weight loss have high predictive value for organic disease in suspected IBS patients and can help identify patients requiring further examination but are not recommended as exclusion criteria for IBS.

A Pilot Study of the Waterless Empirical Taste Test.

OBJECTIVES: This study was performed to test the clinical applicability of a new taste test-the waterless empirical taste test (WETT). METHODS: Sixty healthy volunteers and 20 patients with oral cancer were enrolled. They all received the conventional solution-based whole-mouth suprathreshold taste test (WMTT), which contained sucrose, citric acid, sodium chloride, and caffeine solutions for tastants, along with the WETT. The WETT used plastic strips to deliver tastants. The strip was embedded with sucrose, citric acid, sodium chloride, caffeine, or monosodium glutamate taste enhancer in 4 different concentrations. Each strip was tested twice. Thirty of the healthy volunteers received the WETT again to measure a retest reliability. Case-control matching by age and gender was used to compare the scores of WMTT and WETT between 13 healthy volunteers and 13 patients with oral cancer. RESULTS: The correlation was not high between the WMTT and WETT (r < 0.7) whether in the healthy volunteers or in patients with oral cancer. In terms of retest reliability of the WETT, the mean total score was 24.9 ± 7.3 for the first test and 25.8 ± 8.4 for the second test. The intraclass correlation coefficient was 0.85 (P < .001). When case-control matching was performed, the WMTT scores were not significantly different between 13 healthy volunteers and 13 patients with oral cancer (P = .266), but the WETT scores were significantly lower in patients with oral cancer (P = .017). CONCLUSION: This study showed that the results of the WETT were not highly correlated with those of the WMTT. However, its retest reliability was high, and its results were significantly different between the healthy volunteers and the patients with oral cancer.

Adeno-associated virus vector intraperitoneal injection induces colonic mucosa and submucosa transduction and alters the diversity and composition of the faecal microbiota in rats.

Background: Viral vector technology, especially recombinant adeno-associated virus vector (rAAV) technology, has shown great promise in preclinical research for clinical applications. Several studies have confirmed that rAAV can successfully transduce the enteric nervous system (ENS), and rAAV gene therapy has been approved by the Food and Drug Administration (FDA) for the treatment of the early childhood blindness disease Leber congenital amaurosis and spinal muscular atrophy (SMA). However, until now, it has not been possible to determine the effect of AAV9 on intestinal microbiota. Methods: We examined the efficiency of AAV9-mediated ascending colon, transverse colon and descending colon transduction through intraperitoneal (IP) injection, performed 16S rRNA gene amplicon sequencing and analysed specific faecal microbial signatures following AAV9 IP injection via bioinformatics methods in Sprague-Dawley (SD) rats. Results: Our results showed (1) efficient transduction of the mucosa and submucosa of the ascending, transverse, and descending colon following AAV9 IP injection; (2) a decreased alpha diversity and an altered overall microbial composition following AAV9 IP injection; (3) significant enrichments in a total of 5 phyla, 10 classes, 13 orders, 15 families, 29 genera, and 230 OTUs following AAV9 IP injection; and (4) AAV9 can significantly upregulate the relative abundance of anaerobic microbiota which is one of the seven high-level phenotypes that BugBase could predict. Conclusion: In summary, these data show that IP injection of AAV9 can successfully induce the transduction of the colonic mucosa and submucosa and alter the diversity and composition of the faecal microbiota in rats.

Engineering Advanced Drug Delivery Systems for Dry Eye: A Review.

Dry eye disease (DED) is a widespread and frequently reported multifactorial ocular disease that not only causes ocular discomfort but also damages the cornea and conjunctiva. At present, topical administration is the most common treatment modality for DED. Due to the existence of multiple biological barriers, instilled drugs generally exhibit short action times and poor penetration on the ocular surface. To resolve these issues, several advanced drug delivery systems have been proposed. This review discusses new dosage forms of drugs for the treatment of DED in terms of their characteristics and advantages. Innovative formulations that are currently available in the market and under clinical investigation are elaborated. Meanwhile, their deficiencies are discussed. It is envisioned that the flourishing of advanced drug delivery systems will lead to improved management of DED in the near future.

Influence of age and sex on taste function of healthy subjects.

The purpose of this study was to determine the influence of age and sex on the taste functions of healthy Taiwanese. Subjects were divided into groups based on their sex and age: 20-39 years, 40-59 years, or ≥ 60 years. We evaluated the taste functions of subjects using the whole mouth suprathreshold taste test and the taste quad test. For the whole-mouth test, subjects were instructed to sip and swish sweet, sour, salty, and bitter solutions, each at 5 different suprathreshold concentrations. Each subject was required to indicate the taste quality, and to rate the intensity and unpleasantness/pleasantness of each taste of the solutions. For the quad test, the 4 quadrants of the tongue surface were tested by applying a drop of one concentration of sweet, sour, salty, or bitter solutions 6 times. Subjects then indicated the taste quality and rated the intensity of the solution. We found that in the whole mouth test, the total correct identification score dropped with age, but the ability to identify sweet and salty qualities was not affected by age. No differences were found between males and females, except women scored better than men for sweetness in the 40-59 years age group. The intensity rating scores were higher in the 20-39 years age group, regardless of sex. With regard to the pleasantness of tastants, female subjects in the 20-39 years age group found sweet solution more pleasant than the older subjects did. In the quad test, the total correct identification score decreased with age, but there were no differences between males and females. Thus, our findings showed that both age and sex affected the taste functions of healthy Taiwanese to some extent, and differences were dependent on tongue region and taste quality.

Predictors of nasal bacterial culture rates in patients with chronic rhinosinusitis.

All nontechnical factors were analyzed to predict nasal bacterial culture results in patients with chronic rhinosinusitis (CRS). Four hundred and ninety-six CRS patients, who underwent functional endoscopic sinus surgery (FESS), were enrolled. Prior to FESS, the severity of each patient's CRS was evaluated using a questionnaire, endoscopic examination, acoustic rhinometry, smell test, saccharine transit test, and CT scan. Nasal bacterial cultures were collected from both middle meati using a cotton-tipped stick. Our results showed that the symptom severity complained of by patients and their loss of smell function did not influence the bacterial culture rate. We discovered that the bacterial culture rate was significantly higher in nostrils with nasal polyps than those without polyps, along with nostrils experiencing thick, purulent discharge as opposed to those without discharge. Additionally, this result also occurred in nostrils with a saccharin transit time of more than 30 min than it did in those with a saccharin transit time of less than or equal to 30 min. Both the total endoscopic score and anterior group CT score were significantly higher in nostrils with positive culture than those with negative culture, while the second minimal cross-sectional area (MCA2) of the nasal cavity was significantly lower in nostrils with positive culture than those with negative culture. Multiple logistic regression analysis showed that both nasal polyps and MCA2 were the predictors for positive nasal bacterial culture results. It was concluded that nasal polyps and MCA2 were the predictors for positive nasal bacterial culture results in CRS patients.

miR-222 targets ACOX1, promotes triglyceride accumulation in hepatocytes.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases. However, the exact pathogenesis of NAFLD remains to be elucidated. Despite the association with tumors and cardiovascular diseases, the role of miR-222 in NAFLD remains unclear. The present study was to investigate the role of miR-222 in NAFLD. METHODS: Wild-type C57BL/6 mice were fed a high-fat diet for 12 weeks to induce NAFLD. Normal human liver cell line (L02) was cultured with free fatty acid (FFA)-containing medium to stimulate cell steatosis. The mRNA levels of miR-222 and acyl Coenzyme A xidase 1 (ACOX1) were detected by quantitative-PCR (Q-PCR). The prediction of ACOX1 as the target gene for miR-222 was conducted via TargetScan. The overexpression or inhibition of miR-222 was mediated by miR-222 mimics or antagomir, and intracellular triglyceride levels were measured using a triglyceride kit. Luciferase reporter assays verified ACOX1 as the target gene for miR-222. RESULTS: miR-222 was significantly elevated in both the in vivo and in vitro NAFLD models. Overexpression of miR-222 significantly increased triglyceride content in the L02 cells, while inhibition of miR-222 expression restricted the accumulation of triglyceride. Overexpression of miR-222 significantly inhibited ACOX1 expression. Transient transfection assays verified that ACOX1 3'-UTR luciferase reporter activity could be inhibited by miR-222 overexpression. CONCLUSIONS: The present study suggested that miR-222 promotes the accumulation of triglycerides by inhibiting ACOX1.

The roles of PDGFRα signaling in the postnatal development and functional maintenance of the SMC-ICC-PDGFRα+ cell (SIP) syncytium in the colon.

BACKGROUND: The SIP syncytium in the gut consists of smooth muscle cells, interstitial cells of Cajal, and PDGFRα+ cells. We studied the fate of SIP cells after blocking PDGFRα receptor to explore the roles of PDGFRα signaling in the postnatal development and functional maintenance of the SIP syncytium. METHODS: Crenolanib was administered to mice from P0, P10, or P50. The morphological changes in SIP cells were examined by immunofluorescence. Protein expression in SIP cells was detected by Western blotting. Moreover, colonic transit was analyzed by testing the colonic bead expulsion time. KEY RESULTS: A dose of 5 mg(kg•day)-1 crenolanib administered for 10 days beginning on P0 apparently hindered the development of PDGFRα+ cells in the colonic longitudinal muscularis and myenteric plexus without influencing their proliferative activity and apoptosis, but this result was not seen in the colonic circular muscularis. SMCs were also inhibited by crenolanib. A dose of 7.5 mg(kg•day)-1 crenolanib administered for 15 days beginning on P0 caused reductions in both PDGFRα+ cells and ICC in the longitudinal muscularis, myenteric plexus, and circular muscularis. However, when crenolanib was administered at a dose of 5 mg(kg•day)-1 beginning on P10 or P50, it only noticeably decreased the number of PDGFRα+ cells in the colonic longitudinal muscularis. Crenolanib also caused PDGFRα+ cells to transdifferentiate into SMC in adult mice. Colonic transit was delayed after administration of crenolanib. CONCLUSIONS & INFERENCES: Therefore, PDGFRα signaling is essential for the development and functional maintenance of the SIP cells, especially PDGFRα+ cells.

Impact of antibiotics on smell dysfunction.

OBJECTIVE: Viral or bacterial respiratory infections can cause long-lasting olfactory dysfunction. Antibiotic therapy is indicated in severe cases; however, it is unclear whether antibiotic use produces a positive, negative, or null effect on olfactory function. This retrospective study sought to determine whether antibiotic use has an influence on odor identification and detection threshold test scores of patients with smell dysfunction secondary to upper respiratory infections (URIs), lower respiratory infections (LRIs), or rhinosinusitis. METHODS: Data from a total of 288 patients presenting to the University of Pennsylvania Smell and Taste Center were evaluated. RESULTS: Patients with a URI etiology who had taken bactericidal antibiotics had lower detection thresholds than did patients who had not taken antibiotics (P < 0.023; analysis of covariance with age and time since infection onset as covariates). Moreover, thresholds were lower for bactericidal antibiotic users than for bacteriostatic antibiotic users with either URI (P = 0.023) or rhinosinusitis (P = 0.028) etiologies. No meaningful influences of antibiotics on the odor identification test scores were evident. CONCLUSIONS: These findings, which need to be confirmed in prospective double-blind studies, suggest that bactericidal antibiotic therapy may be beneficial in mitigating, at least to some degree, chronic decrements in smell sensitivity due to URIs and rhinosinusitis.