BACKGROUND/AIMS: The existence of non-celiac gluten sensitivity has been debated. Indeed, the intestinal and extra-intestinal symptoms of many patients with irritable bowel syndrome (IBS) but without celiac disease or wheat allergy have been shown to improve on a gluten-free diet. Therefore, this study set out to evaluate the effects of gluten on IBS symptoms. METHODS: We performed a double-blind randomized placebo-controlled rechallenge trial in a tertiary care hospital with IBS patients who fulfilled the Rome III criteria. Patients with celiac disease and wheat allergy were appropriately excluded. The participants were administered a gluten-free diet for 4 weeks and were asked to complete a symptom-based questionnaire to assess their overall symptoms, abdominal pain, bloating, wind, and tiredness on the visual analog scale (0-100) at the baseline and every week thereafter. The participants who showed improvement were randomly assigned to one of two groups to receive either a placebo (gluten-free breads) or gluten (whole cereal breads) as a rechallenge for the next 4 weeks. RESULTS: In line with the protocol analysis, 60 patients completed the study. The overall symptom score on the visual analog scale was significantly different between the two groups (P<0.05). Moreover, the patients in the gluten intervention group scored significantly higher in terms of abdominal pain, bloating, and tiredness (P<0.05), and their symptoms worsened within 1 week of the rechallenge. CONCLUSIONS: A gluten diet may worsen the symptoms of IBS patients. Therefore, some form of gluten sensitivity other than celiac disease exists in some of them, and patients with IBS may benefit from gluten restrictions.
Abdominal Pain ; Celiac Disease ; Diet ; Diet, Gluten-Free ; Edible Grain ; Glutens* ; Humans ; Irritable Bowel Syndrome* ; Prospective Studies* ; Tertiary Healthcare ; Visual Analog Scale ; Wheat Hypersensitivity ; Wind

BACKGROUND/AIMS: The existence of non-celiac gluten sensitivity has been debated. Indeed, the intestinal and extra-intestinal symptoms of many patients with irritable bowel syndrome (IBS) but without celiac disease or wheat allergy have been shown to improve on a gluten-free diet. Therefore, this study set out to evaluate the effects of gluten on IBS symptoms. METHODS: We performed a double-blind randomized placebo-controlled rechallenge trial in a tertiary care hospital with IBS patients who fulfilled the Rome III criteria. Patients with celiac disease and wheat allergy were appropriately excluded. The participants were administered a gluten-free diet for 4 weeks and were asked to complete a symptom-based questionnaire to assess their overall symptoms, abdominal pain, bloating, wind, and tiredness on the visual analog scale (0-100) at the baseline and every week thereafter. The participants who showed improvement were randomly assigned to one of two groups to receive either a placebo (gluten-free breads) or gluten (whole cereal breads) as a rechallenge for the next 4 weeks. RESULTS: In line with the protocol analysis, 60 patients completed the study. The overall symptom score on the visual analog scale was significantly different between the two groups (P<0.05). Moreover, the patients in the gluten intervention group scored significantly higher in terms of abdominal pain, bloating, and tiredness (P<0.05), and their symptoms worsened within 1 week of the rechallenge. CONCLUSIONS: A gluten diet may worsen the symptoms of IBS patients. Therefore, some form of gluten sensitivity other than celiac disease exists in some of them, and patients with IBS may benefit from gluten restrictions.
Abdominal Pain ; Celiac Disease ; Diet ; Diet, Gluten-Free ; Edible Grain ; Glutens* ; Humans ; Irritable Bowel Syndrome* ; Prospective Studies* ; Tertiary Healthcare ; Visual Analog Scale ; Wheat Hypersensitivity ; Wind

Objective: To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor. Methods: Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed. Results: Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively. Conclusions: SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Biomarkers, Tumor/analysis* ; Calmodulin-Binding Proteins ; China ; Hemangiopericytoma/pathology* ; Sarcoma/pathology* ; Soft Tissue Neoplasms/pathology*

α-smooth muscle actin (α-SMA) and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironment. We investigated how the expression of α-SMA and tenascin-C was altered in the periodontal ligament (PDL) under orthodontic loading to indirectly reveal the intrinsic mechanical microenvironment in the PDL. In this study, we demonstrated the synergistic effects of transforming growth factor-β1 (TGF-β1) and mechanical tensile or compressive stress on myofibroblast differentiation from human periodontal ligament cells (hPDLCs). The hPDLCs under higher tensile or compressive stress significantly increased their levels of α-SMA and tenascin-C compared with those under lower tensile or compressive stress. A similar trend was observed in the tension and compression areas of the PDL under continuous light or heavy orthodontic load in rats. During the time-course analysis of expression, we observed that an increase in α-SMA levels was matched by an increase in tenascin-C levels in the PDL under orthodontic load in vivo. The time-dependent variation of α-SMA and tenascin-C expression in the PDL may indicate the time-dependent variation of intrinsic stress under constant extrinsic loading.
Actins ; analysis ; drug effects ; Adult ; Animals ; Biomechanical Phenomena ; Cell Culture Techniques ; Cell Differentiation ; physiology ; Cells, Cultured ; Cellular Microenvironment ; physiology ; Humans ; Male ; Myofibroblasts ; physiology ; Orthodontic Wires ; Periodontal Ligament ; chemistry ; cytology ; Pressure ; Rats ; Rats, Sprague-Dawley ; Stress, Mechanical ; Tenascin ; analysis ; drug effects ; Time Factors ; Tooth Movement Techniques ; instrumentation ; Transforming Growth Factor beta1 ; pharmacology

Objective: To investigate the prevalence of diphenoxylate abuse and related factors of forced drug abstainer in Gansu province. Methods: By using a self-designed questionnaire, an epidemiologic investigation was carried out among 2 108 forced drug abstainer selected from the compulsory isolation detoxification center of Gansu province. A case-control study was conducted to analyze the factors related with diphenoxylate abuse. Results: The diphenoxylate abuse rate among forced drug abstainer in Gansu was 19.8% (406/2 046), ranking first in medical drug abuse. Multiple logistic regression analysis showed that factors as relieving withdrawal symptoms (OR=2.08, 95%CI: 1.01- 4.32), ways to obtain diphenoxylate (other ways: OR=1.00; regular clinic: OR=27.67, 95%CI: 2.64-289.82; friend: OR=0.01, 95%CI: 0.01-0.03), degree of euphoria (high: OR=1.00; medium: OR =3.36, 95%CI: 1.18-9.55; low: OR=26.16, 95%CI: 10.30-66.42), years of drug abuse (<5 years: OR=1.00; 10-15 years: OR=2.48, 95%CI: 1.02-6.04), abuse at home or in friend's house (OR=3.04, 95%CI: 1.08-8.68), abuse in car (OR=0.05, 95%CI: 0.00-0.68) and detoxification for the first time (OR=0.61, 95%CI: 0.43-0.86) were the possible influencing factors for diphenoxylate abuse. Conclusions: The prevalence of diphenoxylate abuse in forced drug abstainer in Gansu was relatively high. Reasons of abusing, the way to obtain diphenoxylate, whether using drug together with friends, degree of euphoria, years of abuse, abuse place and times for detoxification were related factors influencing the abuse of diphenoxylate.
Analgesics, Opioid/supply & distribution* ; Case-Control Studies ; China ; Diphenoxylate/supply & distribution* ; Humans ; Substance Withdrawal Syndrome ; Substance-Related Disorders/psychology* ; Surveys and Questionnaires

Objective: To investigate the efficacy of neoadjuvant therapy (NAT) on HER2-positive breast cancer and to analyze their clinicopathological features. Methods: A total of 480 cases of HER2-positive breast cancer who received neoadjuvant therapy (NAT), diagnosed at the Department of Pathology of Fudan University Shanghai Cancer Center from 2015 to 2020, were retrospectively identified. Clinicopathological parameters such as age, tumor size, molecular subtype, type of targeted therapy, Ki-67 proliferation index, ER and HER2 immunohistochemical expression, and HER2 amplification status were analyzed to correlate with the efficacy of NAT. Results: Among 480 patients with HER2-positive breast cancer, 209 achieved pathology complete response (pCR) after NAT, with a pCR rate of 43.5%. Of all the cases,457 patients received chemotherapy plus trastuzumab and 23 patients received chemotherapy with trastuzumab and pertuzumab. A total of 198 cases (43.3%) achieved pCR in patients with chemotherapy plus trastuzumab, and 11 cases (47.8%) achieved pCR in patients with chemotherapy plus trastuzumab and pertuzumab. The pCR rate in the latter group was higher, but there was no statistical significance. The results showed that the pCR rate of IHC-HER2 3+patients (49%) was significantly higher than that of IHC-HER2 2+patients (26.1%, P<0.001). The higher the mean HER2 copy number in the FISH assay, the higher the pCR rate was achieved. The expression level of ER was inversely correlated with the efficacy of NAT, and the pCR rate in the ER-positive group (28.2%) was significantly lower than that in the ER-negative group (55.8%, P<0.001). The pCR rate (29.1%) of patients with luminal B type was lower than that of HER2 overexpression type (55.8%, P<0.001). In addition, higher Ki-67 proliferation index was associated with higher pCR rate (P<0.001). The pCR rate was the highest in the tumor ≤2 cm group (57.7%), while the pCR rate in the tumor >5 cm group was the lowest (31.1%). The difference between the groups was significant (P=0.005). Conclusions: HER2 copy numbers, HER2 immunohistochemical expression level, molecular subtype, ER expression level and Ki-67 proliferation index are significantly associated with pCR after NAT. In addition, fluorescence in situ hybridization results, HER2/CEP17 ratio and tumor size could also significantly affect the efficacy of NAT.
China ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen ; Neoadjuvant Therapy ; Retrospective Studies ; Trastuzumab ; Humans ; Female ; Breast Neoplasms/drug therapy*

Background and Objectives: Heart Failure (HF) remains a major health concern worldwide. In the Philippine General Hospital (PGH), HF is consistently a top cause of mortality and readmissions among adults. The American College of Cardiology (ACC) and European Society of Cardiology (ESC) published guidelines for interventions that improve quality of life and survival, but they are underused and untested for local acceptability. Hospitals overseas used order sets created from these guidelines, which resulted in a considerable decrease in in-hospital mortality and healthcare costs. We aimed to develop an order set for adult patients with acute heart failure (AHF) admitted to the PGH Emergency Department (ED) to improve care outcomes. Methods: This study utilized a mixed methods approach to create the AHF order set. ESC and ACC HF guidelines were appraised using the AGREE II tool. Class I interventions for AHF were included in the initial order set. Through focused group discussions (FGD), clinicians and other care team members involved in the management of AHF patients at PGH ED modified and validated the order set. Stakeholders were asked to use online Delphi and FGD to get a consensus on how to amend, approve, and carry out the order given. Results: Upon review of HF guidelines, 29 recommendations on patient monitoring, initial diagnostic, and therapeutic interventions were adopted in the order set. Orders on subspecialty referrals and ED disposition were introduced. The AHF patient was operationally defined in the setting of PGH ED. The clinical orders fit the PGH context, ensuring evidence-based, cost-effective, and accessible care responsiveness to patients’ needs and suitable for local practice. Workflow changes due to COVID-19 were considered. Potential barriers to implementation were identified and addressed. The final order set was adopted for implementation through stakeholder consensus. Conclusion The PGH developed and adopted its own AHF order set that is locally applicable and can potentially optimize outcomes of care.
Quality Improvement ; Critical Pathways