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Abstract Background Multiple epiphyseal dysplasia (MED) is a rare congenital bone dysplasia. Patients with MED develop secondary hip osteoarthritis as early as the third to the fourth decade. Currently, there is no consensus on the prevention of the progressive hip osteoarthritis secondary to MED. The Bernese periacetabular osteotomy (PAO) is a joint-preserving surgery to reshape acetabulum and extend femoral head coverage. However, there is no documentary evidence for the effect of the procedure on MED hips. Patients and methods We analyzed the preliminary outcomes following the Bernese PAO in 6 MED hips. The average age at the time of surgery was 14.3 years (range from 11.4 to 17.2 years). For our study interest of time efficiency, radiographic parameters were analyzed preoperatively and 1 year postoperatively. The hip function was evaluated by the Harris Hip Score (HHS) before and after surgery. Results The mean follow-up time was 1.7 years. The mean lateral center–edge angle increased from 3.8° to 47.1° (p = 0.02), anterior center–edge angle increased from 7.3° to 35.1° (p = 0.02), and acetabulum index decreased from 27.8° to 14.6° (p = 0.04). The femoral head coverage ratio increased from 66.8% to 100% (p = 0.02). The post-operative anteroposterior pelvic radiograph demonstrated all preoperative broken Shenton lines were reversed. The mean HHS improved from 67.3 to 86.7 (p = 0.05). Conclusion Bernese PAO is a feasible treatment for hip disorders in MED patients. It reshapes acetabular and femoral morphology efficiently. In our study, the preliminary results showed the procedure not only improved radiographic outcomes but also hip function.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive fat accumulation in the liver. Intracellular oxidative stress induced by lipid accumulation leads to various hepatocellular injuries including fibrosis. However, no effective method for mitigating MASLD without substantial side effects currently exists. Molecular hydrogen (H2) has garnered attention due to its efficiency in neutralizing harmful reactive oxygen species (ROS) and its ability to penetrate cell membranes. Some clinical evidence suggests that H2 may alleviate fatty liver disease, but the precise molecular mechanisms, particularly the regulation of lipid droplet (LD) metabolism, remain unclear. This study utilized an in vitro model of hepatocyte lipid accumulation induced by free fatty acids (FFAs) to replicate MASLD in HepG2 cells. The results demonstrated a significant increase in LD accumulation due to elevated FFA levels. However, the addition of hydrogen-rich water (HRW) effectively reduced LD accumulation. HRW decreased the diameter of LDs and reduced lipid peroxidation and FFA-induced oxidative stress by activating the AMPK/Nrf2/HO-1 pathway. Overall, our findings suggest that HRW has potential as an adjunctive supplement in managing fatty liver disease by reducing LD accumulation and enhancing antioxidant pathways, presenting a novel strategy for impeding MASLD progression.

IntroductionThe impact of climate change on ambient temperatures threatens to worsen pediatric pneumonia-related outcomes considerably. This study examined the associations of temperature variation and extreme temperature with pediatric pneumonia-related events using a meta-analysis.MethodsWe systematically searched PubMed, Medline, Embase, and Web of Science databases for relevant literature, and the quality of evidence was assessed. Fixed and random-effects meta-analyses were performed to calculate the pooled relative risks (RRs) of the associations with pneumonia-related events.ResultsWe observed that a 1°C temperature variation increased the RR of pneumonia events by 1.06-fold (95% confidence interval (CI): 1.03–1.10). A 1°C temperature variation increased the RR by 1.10-fold of the pediatric pneumonia hospital admissions (95% CI: 1.00–1.21) and 1.06-fold of the pediatric pneumonia emergency department visits (95% CI: 1.01-1.10). Extreme cold increased the RR by 1.25-fold of the pediatric pneumonia events (95% CI: 1.07–1.45). A 1°C temperature variation increased the RR of pneumonia events in children by 1.19-fold (95% CI: 1.08–1.32), girls by 1.03-fold (95% CI: 1.02–1.05), and in temperate climate zones by 1.07-fold (95% CI: 1.03–1.11). Moreover, an increase in extreme cold increased the RR of pneumonia events in children by 2.43-fold (95% CI: 1.72–3.43), girls by 1.96-fold (95% CI: 1.29–2.98) and in temperate climate zones by 2.76-fold (95% CI: 1.71–4.47).ConclusionOur study demonstrated that pediatric pneumonia events are more prevalent among children, particularly girls, and individuals residing in temperate climate zones. Climate change represents an emergent public health threat, affecting pediatric pneumonia treatment and prevention..Systematic Review RegistrationPROSPERO (CRD42022378610).

AbstractPre-trained language models have been successful in many knowledge-intensive NLP tasks. However, recent work has shown that models such as BERT are not “structurally ready” to aggregate textual information into a [CLS] vector for dense passage retrieval (DPR). This “lack of readiness” results from the gap between language model pre-training and DPR fine-tuning. Previous solutions call for computationally expensive techniques such as hard negative mining, cross-encoder distillation, and further pre-training to learn a robust DPR model. In this work, we instead propose to fully exploit knowledge in a pre-trained language model for DPR by aggregating the contextualized token embeddings into a dense vector, which we call agg★. By concatenating vectors from the [CLS] token and agg★, our Aggretriever model substantially improves the effectiveness of dense retrieval models on both in-domain and zero-shot evaluations without introducing substantial training overhead. Code is available at https://github.com/castorini/dhr.

Abstract Background Ovarian cancer has the highest mortality among gynecological cancers due to late diagnosis and lack of effective targeted therapy. Although the study of interplay between cancer cells with their microenvironment is emerging, how ovarian cancer triggers signaling that coordinates with immune cells to promote metastasis is still elusive. Methods Microarray and bioinformatics analysis of low and highly invasive ovarian cancer cell lines were used to reveal periostin (POSTN), a matrix protein with multifunctions in cancer, with elevated expression in the highly invasive cells. Anchorage independent assay, Western blot, RNA interference, confocal analysis and neutralizing antibody treatment were performed to analyze the effects of POSTN on tumor promotion and to explore the underlying mechanism. Chemotaxis, flow cytometry and cytokine array analyses were undertaken to analyze the involvement of POSTN in cancer-associated fibroblast (CAF) and macrophage modulation. Correlations between POSTN expression levels and clinical characteristics were analyzed using the Oncomine, commercial ovarian cancer cDNA and China Medical University Hospital patient cohort. In vivo effect of POSTN on metastasis was studied using a mouse xenograft model. Results Expression of POSTN was found to be elevated in highly invasive ovarian cancer cells. We observed that POSTN was co-localized with integrin β3 and integrin β5, which was important for POSTN-mediated activation of ERK and NF-κB. Ectopic expression of POSTN enhanced whereas knockdown of POSTN decreased cancer cell migration and invasion in vitro, as well as tumor growth and metastasis in vivo. POSTN enhanced integrin/ERK/NF-κB signaling through an autocrine effect on cancer cells to produce macrophage attracting and mobilizing cytokines including MIP-1β, MCP-1, TNFα and RANTES resulting in increased chemotaxis of THP-1 monocytes and their polarization to M2 macrophages in vitro. In agreement, tumors derived from POSTN-overexpressing SKOV3 harbored more tumor-associated macrophages than the control tumors. POSTN induced TGF-β2 expression from ovarian cancer cells to promote activation of adipose-derived stromal cells to become CAF-like cells expressing alpha smooth muscle actin and fibroblast activation protein alpha. Consistently, increased CAFs were observed in POSTN overexpressing SKOV3 cells-derived metastatic tumors. In clinical relevance, we found that expression of POSTN was positively correlated with advanced-stage diseases and poor overall survival of patients. Conclusions Our study revealed a POSTN-integrin-NF-κB-mediated signaling and its involvement in enhancing M2 macrophages and CAFs, which could potentially participate in promoting tumor growth. Our results suggest that POSTN could be a useful prognosis marker and potential therapeutic target.

Norovirus infection is a leading cause of acute gastroenteritis worldwide and can also cause harmful chronic infections in individuals with weakened immune systems. The role of the gut microbiota in the interactions between the host and noroviruses has been extensively studied. While most past studies were conducted in vitro or focused on murine noroviruses, recent research has expanded to human noroviruses using in vivo or ex vivo human intestinal enteroids culture studies. The gut microbiota has been observed to have both promoting and inhibiting effects on human noroviruses. Understanding the interaction between noroviruses and the gut microbiota or probiotics is crucial for studying the pathogenesis of norovirus infection and its potential implications, including probiotics and vaccines for infection control. Recently, several clinical trials of probiotics and norovirus vaccines have also been published. Therefore, in this review, we discuss the current understanding and recent updates on the interactions between noroviruses and gut microbiota, including the impact of norovirus on the microbiota profile, pro-viral and antiviral effects of microbiota on norovirus infection, the use of probiotics for treating norovirus infections, and human norovirus vaccine development.

Background: Climate change's influence on extreme weather events poses a significant threat to the morbidity and mortality of asthma patients. The aim of this study was to examine associations between extreme weather events and asthma-related outcomes. Methods: A systematic literature search for relevant studies was performed using the PubMed, EMBASE, Web of Science and ProQuest databases. Fixed-effects and random-effects models were applied to estimate the effects of extreme weather events on asthma-related outcomes. Results: We observed that extreme weather events were associated with increasing risks of general asthma outcomes with relative risks of 1.18-fold for asthma events (95% CI 1.13–1.24), 1.10-fold for asthma symptoms (95% CI 1.03–1.18) and 1.09-fold for asthma diagnoses (95% CI 1.00–1.19). Extreme weather events were associated with increased risks of acute asthma exacerbation with risk ratios of asthma emergency department visits of 1.25-fold (95% CI 1.14–1.37), of asthma hospital admissions of 1.10-fold (95% CI 1.04–1.17), of asthma outpatient visits of 1.19-fold (95% CI 1.06–1.34) and of asthma mortality of 2.10-fold (95% CI 1.35–3.27). Additionally, an increase in extreme weather events increased risk ratios of asthma events by 1.19-fold in children and 1.29-fold in females (95% CI 1.08–1.32 and 95% CI 0.98–1.69, respectively). Thunderstorms increased the risk ratio of asthma events by 1.24-fold (95% CI 1.13–1.36). Conclusions: Our study showed that extreme weather events more prominently increased the risk of asthma morbidity and mortality in children and females. Climate change is a critical concern for asthma control.

Abstract Background The development of drug resistance in oral squamous cell carcinoma (OSCC) that frequently leads to recurrence and metastasis after initial treatment remains an unresolved challenge. Presence of cancer stem cells (CSCs) has been increasingly reported to be a critical contributing factor in drug resistance, tumor recurrence and metastasis. Thus, unveiling of mechanisms regulating CSCs and potential targets for developing their inhibitors will be instrumental for improving OSCC therapy. Methods siRNA, shRNA and miRNA that specifically target keratin 17 (KRT17) were used for modulation of gene expression and functional analyses. Sphere-formation and invasion/migration assays were utilized to assess cancer cell stemness and epithelial mesenchymal transition (EMT) properties, respectively. Duolink proximity ligation assay (PLA) was used to examine molecular proximity between KRT17 and plectin, which is a large protein that binds cytoskeleton components. Cell proliferation assay was employed to evaluate growth rates and viability of oral cancer cells treated with cisplatin, carboplatin or dasatinib. Xenograft mouse tumor model was used to evaluate the effect of KRT17- knockdown in OSCC cells on tumor growth and drug sensitization. Results Significantly elevated expression of KRT17 in highly invasive OSCC cell lines and advanced tumor specimens were observed and high KRT17 expression was correlated with poor overall survival. KRT17 gene silencing in OSCC cells attenuated their stemness properties including markedly reduced sphere forming ability and expression of stemness and EMT markers. We identified a novel signaling cascade orchestrated by KRT17 where its association with plectin resulted in activation of integrin β4/α6, increased phosphorylation of FAK, Src and ERK, as well as stabilization and nuclear translocation of β-catenin. The activation of this signaling cascade was correlated with enhanced OSCC cancer stemness and elevated expression of CD44 and epidermal growth factor receptor (EGFR). We identified and demonstrated KRT17 to be a direct target of miRNA-485-5p. Ectopic expression of miRNA-485-5p inhibited OSCC sphere formation and caused sensitization of cancer cells towards cisplatin and carboplatin, which could be significantly rescued by KRT17 overexpression. Dasatinib treatment that inhibited KRT17-mediated Src activation also resulted in OSCC drug sensitization. In OSCC xenograft mouse model, KRT17 knockdown significantly inhibited tumor growth, and combinatorial treatment with cisplatin elicited a greater tumor inhibitory effect. Consistently, markedly reduced levels of integrin β4, active β-catenin, CD44 and EGFR were observed in the tumors induced by KRT17 knockdown OSCC cells. Conclusions A novel miRNA-485-5p/KRT17/integrin/FAK/Src/ERK/β-catenin signaling pathway is unveiled to modulate OSCC cancer stemness and drug resistance to the common first-line chemotherapeutics. This provides a potential new therapeutic strategy to inhibit OSCC stem cells and counter chemoresistance.

Background: Osteoporosis increases the fracture and mortality risk of patients and has a higher disease burden than some cancers. Therefore, global concerns regarding the prevention and treatment of osteoporosis have been raised. However, fast-aging Taiwan lacks national epidemiological data on osteoporosis in recent years. We aimed to establish and update epidemiological data on osteoporosis by analyzing national data from 2008 to 2019. Methods: We estimated the prevalence and incidence of osteoporosis in patients aged ≥50 years based on claims data from Taiwan's National Health Insurance database from 2008 to 2019. We also analyzed the key parameters of fracture care (anti-osteoporosis medication use, bone mineral density examination rate, and length of hospital stay) to understand the secular trend of management and related clinical outcomes (imminent refracture rate and mortality). Results: The number of prevalent osteoporosis increased from 2008 to 2015 and remained constant until 2019; however, the age-standardized prevalence and incidence rates declined from 2008 to 2019 (3.77%–2.91% and 2.08%–1.02%, respectively). The overall incidence rates of hip and spine fractures decreased significantly by 34% and 27%, respectively. For patients with hip and spine fractures, the immanent refracture rates were 8.5% and 12.9% and the 1-year mortality rate remained stable at approximately 15% and 6%, respectively. Conclusion: The age-standardized prevalence and incidence rates decreased remarkably from 2008 to 2019, while the number of prevalent osteoporosis remained steady. Patients with hip fractures encountered a high 1-year mortality rate, while the risk of imminent refracture was notable for patients with spine fractures.

Background: Adherence to anti-osteoporosis medications (AOMs) is crucial. National Health Insurance (NHI) in Taiwan has its own rules of reimbursement rule for AOMs. The midterm adherence remained inconclusive. Here we investigated the adherence according to the initially used AOMs, for three consecutive years. Methods: The nationwide cohort study from 2008 to 2018, based on Taiwan's National Health Insurance Research Database, included 336,229 patients. Their adherence, indicated by medication possession ratio (MPR), to the initial AOMs was investigated yearly for three consecutive years. The overall MPRs (OMPR), including the switched AOMs, were also calculated in the first year. The Sankey diagram further visualized the patient flows toward different adherence according to the initial AOMs. Results: The OMPR in the first year improved if the patients used AOMs with longer dosing intervals. 100%, 68.9%, 40.7%, and 34.0% of the patients started the treatment with zoledronate, denosumab, alendronate, and raloxifene, respectively, had OMPR ≥75% in the first year. In the 3rd year, only 20.89%, 24.13%, and 12.83% of the patients continuously treated with zoledronate, denosumab, and alendronate, respectively, had MPR ≥75%. From the Sankey diagram, we also observed that patients who had poor adherence at one year were inclined to have poor adherence or discontinue antiosteoporosis treatment in the next year. Conclusion: The initial AOMs and the observed adherence may provide clues for optimizing patient treatment. The real-world adherence in Taiwan was far from satisfactory in our study.

Background: The objective of this research was to report the trend of osteoporosis care after hip fractures from usual care (UC) and to compare the quality of care with those who received fracture liaison services (FLSs). Methods: Data on osteoporosis care for patients with hip fracture were acquired from the National Health Insurance claims (UC group), and surveys from FLS programs (FLS group). A total of 183,300 patients receiving UC and 3010 patients receiving FLS were studied. For the two groups, common osteoporosis care indicators, such as bone mineral density (BMD) testing rate, antiosteoporosis medication commencement rate, and adherence rate were described. Results: There were 2488 participants (82.7%) in the FLS group who completed Dual-energy X-ray absorptiometry (DXA) in 8 weeks, 155 (5.1%) who finished it between 8 weeks and 1 year. Even in 2018, when the DXA completion rate was at its highest, the completion rate in the UC group was only 23.5%. In terms of medication commencement, 2372 FLS patients (78.8%) received treatment within 3 months. Only 24.9% of the UC patients received antiosteoporosis medication within 3 months. Furthermore, antiosteoporosis medication adherence rate was 92.2% after 1 year and 83.9% after 2 years in the FLS group, but these were only 66.5% and 42.7%, respectively, in the UC group. Conclusion: Patients who received FLS had more timely BMD exams, antiosteoporosis medication treatment, and higher adherence to antiosteoporosis therapy than those who received UC. The discrepancy in rates of continuing treatment became more significant over time between both groups.

Abstract Certain immune cells and inflammatory cytokines are essential components in the tumor microenvironment to promote breast cancer progression. To identify key immune players in the tumor microenvironment, we applied highly invasive MDA-MB-231 breast cancer cell lines to co-culture with human monocyte THP-1 cells and identified CXCL7 by cytokine array as one of the increasingly secreted cytokines by THP-1 cells. Further investigations indicated that upon co-culturing, breast cancer cells secreted CSF1 to induce expression and release of CXCL7 from monocytes, which in turn acted on cancer cells to promote FAK activation, MMP13 expression, migration, and invasion. In a xenograft mouse model, administration of CXCL7 antibodies significantly reduced abundance of M2 macrophages in tumor microenvironment, as well as decreased tumor growth and distant metastasis. Clinical investigation further suggested that high CXCL7 expression is correlated with breast cancer progression and poor overall survival of patients. Overall, our study unveils an important immune cytokine, CXCL7, which is secreted by tumor infiltrating monocytes, to stimulate cancer cell migration, invasion, and metastasis, contributing to the promotion of breast cancer progression.

Coronaviruses can cause pneumonia, with clinical symptoms that may be similar to the symptoms of other viral pneumonias. To our knowledge, there have been no reports regarding cases of pneumonia caused by coronaviruses and other viruses among hospitalized patients in the past 3 years before and during coronavirus disease 2019 (COVID-19). Here, we analysed the causes of viral pneumonia among hospitalized patients during the coronavirus disease 2019 (COVID-19) pandemic (2019–2021). Between September 2019 and April 2021, patients hospitalized at Shuang Ho Hospital in north Taiwan with a diagnosis of pneumonia were enrolled in this study. Age, sex, onset date, and season of occurrence were recorded. Respiratory tract pathogens were identified with molecular detection using the FilmArray® platform from nasopharyngeal swabs. In total, 1147 patients (128 patients aged 65 years) with pneumonia tested positive for coronavirus most commonly in autumn. Coronavirus was not detected during summer in children or adults. Among children aged 0–6 years, RSV was the most common viral pathogen, and RSV infection occurred most often in autumn. Metapneumovirus infection occurred most often in spring in both children and adults. In contrast, influenza virus was not detected in patients with pneumonia in any season among children or adults from January 2020 to April 2021. Among all patients with pneumonia, the most common viral pathogens were rhinovirus in spring, adenovirus and rhinovirus in summer, RSV and rhinovirus in autumn, and parainfluenza virus in winter. Among children aged 0–6 years, RSV, rhinovirus, and adenovirus were detected in all seasons during the study period. In conclusion, the proportion of pneumonia cases caused by a viral pathogen was higher in children than the proportion in adults. The COVID-19 pandemic period evoked a need for SARS-CoV-2 (severe acute respiratory disease coronavirus 2) vaccination to prevent the severe complications of COVID-19. However, other viruses were also found. Vaccines for influenza were clinically applied. Active vaccines for other viral pathogens such as RSV, rhinovirus, metapneuomoccus, parainfluenza, and adenovirus may need to be developed for special groups in the future.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease. We reported two 7-month-old identical male twins with Pseudomonas aeruginosa sepsis who initially manifested as oral ecthyma gangrenosum and were finally diagnosed to have XLA. In both cases, we confirmed the c.862C > T BTK missense mutation in exon 10 at the SH2 domain.

Proximal femoral varus osteotomy (PFVO) is a common procedure performed in children with developmental dysplasia of the hip (DDH) and Legg–Calvé–Perthes disease (LCPD). However, the long-term effect on angular deformities of the knees and ankles following PFVO remains controversial. This study investigated the relationship between PFVO and alignment changes in the knee and ankle after the procedure. Twenty-five patients undergoing PFVO procedure with a minimum 4-year evaluation period were enrolled in the study, including 14 unilateral LCPD and 11 unilateral DDH. The standing scanogram examinations were collected before the operation, immediately following surgery, after a 1-year follow-up, after a 3-year follow-up, and at the final visit to the clinic. The radiographic parameters included leg length, femoral neck-shaft angle (FNSA), femorotibial angle (FTA), mechanical axis deviation (MAD), tibiotalar angle (TTA), and mechanical lateral distal femoral angle (mLDFA). At the final examination, FNSA demonstrated insignificant change between the operative and non-operative limbs in the DDH group. Compared with the postoperative result, FNSA significantly improved in the LCPD group (p = 0.039). Both groups did not develop statistical significance in TTA, mLDFA, MAD, and leg length discrepancy after more than a 5-year follow-up. From a biomechanical perspective that the foot passes more medial to the knee under the center of leg mass, varus knee was prone to develop. In order to correct the mechanical axis, the knee reverted to a valgus position gradually. Our study indicates that patients with LCPD or DDH receiving PFVO and Pemberton osteotomy narrow the gap of angular growth in knees and ankles between the operative and non-operative limbs after a long-term follow-up.

Background: To compare single-incision laparoscopic appendectomy (SILA) with conventional (CLA) and transumbilical laparoscopic appendectomy (TULA). Methods: This is a retrospective cohort study. Patients were divided into three groups, SILA, CLA, and TULA. SILA was defined as performing appendectomy extracorporeally or intracorporeally by using a glove-port incorporated with 3 trocars. TULA was defined as exteriorizing appendix and performing extracorporeal appendectomy by using an operative telescope. Statistical analysis was conducted in patients with simple (SA) and complicated appendicitis (CA), respectively. Results: A total of 315 patients were enrolled, including 161 in SILA, 105 in CLA, and 49 in TULA. Demographic data were similar. In patients with simple appendicitis, operation time of SILA was shorter than CLA but longer than TULA (62.8 ± 22.5 vs. 82.2 ± 24.3 and 51.6 ± 22.3 min, p

Kawasaki disease (KD), also called mucocutaneous lymph node syndrome, is a febrile multisystem vasculitis mainly affecting children younger than 5 years. KD typically manifests as skin lesions and in the lymph nodes and oral and conjunctival mucosa. It may induce coronary artery abnormalities, such as aneurysms, but gastrointestinal and hepatobiliary involvement are not common. We reviewed 32 cases of patients with a diagnosis of KD with hepatobiliary involvement between 2000 and 2021 and present the case of a 4-year-old girl who received a diagnosis of KD with combined cholestatic hepatitis and Mycoplasma pneumoniae infection. In the 33 cases reviewed, in addition to the classical clinical findings of KD, the most common clinical presentations were jaundice and abdominal pain. Moreover, abnormal laboratory results indicating hyperbilirubinemia, cholestasis, and hepatitis, among other conditions, were noted. Abdominal ultrasonography revealed abnormal findings in more than half children with KD with hepatobiliary involvement. Furthermore, cardiac involvement was noted in a high proportion of the patients. In particular, we noted the case of a 4-year-old girl with a rare presentation of 3-day fever combined with abdominal pain and jaundice. Her levels of aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, alkaline phosphatase, and γ-glutamyl transpeptidase were 489 (15–50) U/L, 253 (5–45) U/L, 4.3 (

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with the colorectum as its major target organ. Involvement of the upper gastrointestinal tract in UC is rare and presents with nonspecific endoscopic and microscopic characteristics. Recent studies have demonstrated proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) to be a serological marker for differentiating UC from Crohn's disease in children and for detecting disease activity and nonresponse to steroid therapy and antitumor necrotizing factor-α agents. Herein, we report a 13-year-old female patient mainly presenting with recurrent bilious vomiting who was initially diagnosed with acute gastroenteritis. Intestinal pseudo-obstruction was confirmed through observation of a patent but segmentally dilated jejunum in the barium follow-through examination and other imaging; such obstruction can be attributed to backwash ileitis, superior mesenteric artery syndrome, ileus due to hypokalemia, or PR3-associated enteritis. Laboratory data revealed leukocytosis with neutrophil predominance and serum antinuclear antibody and PR3-ANCA positivity. Overlapping syndrome with autoimmune diseases was suspected. Pathology revealed a crypt abscess with aggregates of neutrophils consistent with UC but did not indicate vasculitis. The in situ immunohistochemical staining revealed PR3 density mainly in the colon and focally in the duodenum. To our knowledge, this is the first case report with in situ pathological evidence of PR3 in inflamed intestinal tissues in a patient with UC and with rare initial presentation of intestinal pseudo-obstruction–induced recurrent bilious vomiting. Whether the clinical features of the present case constitute overlap syndrome with other autoimmune disease or a disease variation of UC warrants further investigation. Notably, the patient's serum PR3-ANCA titers remained high in coincidence with increased disease activity and nonresponse to steroid therapy, but became lower after infliximab treatment. PR3-ANCA as a potential serum biomarker to aid in making differential diagnoses of UC in children, correlating disease activity, and predicting therapeutic responses was also reviewed.

Background Norovirus (NoV) infection is common in pediatric patients with immunodeficiency and is more likely to cause severe disease. Objective Our study aims to figure out the clinical differences and distribution of intestinal microbiota in immunocompromised children with NoV gastroenteritis. Methods Pediatric patients admitted to Shang-Ho Hospital with diagnosis of acute gastroenteritis including different immune status were enrolled and their medical records were reviewed. NoV gastroenteritis was validated using RT-PCR molecular methods. Viral shedding period was determined by real-time RT-PCR assays. Intestinal microbiota enrichment analysis was carried out by next generation sequencing after fecal DNA extraction and subsequent Linear Discriminant Analysis (LDA) Effect Size (LEfSe) method. Results Significantly higher frequency of diarrhea [mean, (IQR), 3.8 (3–5) /day] and longer viral shedding time [mean, IQR, 8.5 (5–13) days] was found in immunocompromised NoV infections than in immunocompetent patients without NoV infections (p = 0.013*) and immunocompetent patients with NoV infections (p = 0.030**). The fever prevalence was significantly lower in immunocompromised NoV infections than in different immune or infection status. Intestinal microbiota metagenomics analysis showed no significant community richness difference while the LEfSe analysis showed a significant difference in commensal richness at the phylum level, the family level, and the genus level in patients under different immune status. Conclusion We evaluated the clinical significances and microbiota composition in immunocompromised children with norovirus gastroenteritis. This will further facilitate studies of the interaction between the intestinal microbiota in such patients with precise determination of their bacterial infection control and probiotic supplements strategy.

Diabetic neuropathy (DN) is a type of sensory nerve damage that can occur in patients with diabetes. Although the understanding of pathophysiology is incomplete, DN is often associated with structural and functional alterations of the affected neurons. Among all possible causes of nerve damage, Schwann cells (SCs) are thought to play a key role in repairing peripheral nerve injury, suggesting that functional deficits occurring in SCs may potentially exhibit their pathogenic roles in DN. Therefore, elucidating the mechanisms that underlie this pathology can be used to develop novel therapeutic targets. In this regard, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently attracted great attention in ameliorating SCs’ dysfunction. However, the detailed mechanisms remain uncertain. In the present study, we investigated how GLP-1 RA Liraglutide protects against RSC96 SCs dysfunction through a diabetic condition mimicked by high glucose and high free fatty acid (FFA). Our results showed that high glucose and high FFAs reduced the viability of RSC96 SCs by up to 51%, whereas Liraglutide reduced oxidative stress by upregulating antioxidant enzymes, and thus protected cells from apoptosis. Liraglutide also inhibited NFκB-mediated inflammation, inducing SCs to switch from pro-inflammatory cytokine production to anti-inflammatory cytokine production. Moreover, Liraglutide upregulated the production of neurotrophic factors and myelination-related proteins, and these protective effects appear to be synergistically linked to insulin signaling. Taken together, our findings demonstrate that Liraglutide ameliorates diabetes-related SC dysfunction through the above-mentioned mechanisms, and suggest that modulating GLP-1 signaling in SCs may be a promising strategy against DN.

Noroviruses (NoVs) are one of the emerging and rapidly spreading groups of pathogens threatening human health. A reduction in sporadic NoV infections was noted following the start of the COVID-19 pandemic, but the return of NoV gastroenteritis during the COVID-19 pandemic has been noted recently. Research in recent years has shown that different virus strains are associated with different clinical characteristics; moreover, there is a paucity of research into extraintestinal or unusual complications that may be associated with NoV. The genomic diversity of circulating NoVs is also complex and may vary significantly. Therefore, this short narrative review focuses on sharing the Taiwan experience of NoV infection including epidemiology, clinical features, and complications following suboptimal rotavirus immunization in Taiwan (after October 2006). We also highlight the unusual complications associated with NoV infections and the impacts of NoV infection during the COVID-19 pandemic in the literature for possible future research directions. To conclude, further research is needed to quantify the burden of NoV across the spectrum of disease severity in Taiwan. The evidence of the connection between NoV and the unusual complications is still lacking.

The human body is colonized by a wide range of microorganisms. The field of viromics has expanded since the first reports on the detection of viruses via metagenomic sequencing in 2002. With the continued development of reference materials and databases, viral metagenomic approaches have been used to explore known components of the virome and discover new viruses from various types of samples. The virome has attracted substantial interest since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic. Increasing numbers of studies and review articles have documented the diverse virome in various sites in the human body, as well as interactions between the human host and the virome with regard to health and disease. However, there have been few studies of direct causal relationships. Viral metagenomic analyses often lack standard references and are potentially subject to bias. Moreover, most virome-related review articles have focused on the gut virome and did not investigate the roles of the virome in other sites of the body in human disease. This review presents an overview of viral metagenomics, with updates regarding the relations between alterations in the human virome and the pathogenesis of human diseases, recent findings related to COVID-19, and therapeutic applications related to the human virome.

Congenital tuberculosis (TB) is difficult to detect because the disease presents few or no symptoms in the fetus during pregnancy and nonspecific symptoms in neonates. We reviewed 20 cases of congenital TB reported between 2011 and 2017 and report a case of a mother and her 8 days old neonate with congenital TB. In these 21 cases (including our case), the most common clinical presentations were respiratory distress, fever, and hepatosplenomegaly. The most common chest imaging findings were pneumonia, multiple pulmonary nodules, and miliary pattern. The mortality rate of infants with TB was increased ~2.2-fold if their mothers had no symptoms. The case reported herein concerns an 8 days old neonate with the rare presentation of a 2 days history of fever, followed by abdominal distension without respiratory symptoms. Computed tomography (CT) imaging exhibited a large amount of right pleural effusion. Multiple antimicrobial therapies were administered to the neonate; however, his symptoms persisted. Repeat CT was used to identify a progressed disease with multiple nodules over the lung, spleen, and hepatic hilar region. Standard anti-TB medications were prescribed, and the patient recovered gradually. Both gastric lavage and pleural effusion cultures confirmed the diagnosis of TB. The neonate's mother denied any TB contact history and the diagnosis of any medical disease during pregnancy, but she experienced a fulminant course of miliary TB and was admitted to the intensive care unit 24 days postpartum. She died despite receiving anti-TB treatment. In TB-endemic areas, congenital TB should be taken into consideration when neonates develop fever, respond poorly to antimicrobial treatment, and when their mothers deny any TB contact history.

Introduction : Connective tissue growth factor (CTGF) mediates hypertrophy, proliferation, and extracellular matrix synthesis. Matrix metalloproteinase (MMP) plays a role in airway extracellular matrix remodeling. The correlation between CTGF and MMP in airway remodeling of asthma was unknown. This study investigated lung CTGF expression and its correlation with MMP and airway structural changes in a murine model of asthma. Material and methods : Female BALB/c mice were sensitized and challenged by intraperitoneal injections and intranasal phosphate-buffered saline (PBS) or ovalbumin (OVA). Airway responsiveness and serum OVA-specific IgE were measured. Airway structural changes were quantified by morphometric analysis. Differential cell counts and MMP-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 were evaluated in bronchoalveolar lavage fluid (BALF). Lung CTGF was determined by Western blot. Results : Serum OVA-specific IgE level and airway responsiveness in enhanced pause (Penh) is significantly higher in sensitized mice challenged with OVA compared to PBS-challenged mice. MMP-2, MMP-9, and TIMP-1 in BALF were significantly higher in OVA mice. Airway structural changes of animals’ lungs with OVA challenge showed increased thickness of the smooth muscle layer and numbers of Goblet cells and inflammatory cells and eosinophils near airways and perivascular areas. Lung CTGF expression significantly increased in OVA-challenged mice. CTGF expressions positively correlated with MMP-9 (r = 0.677, p < 0.05), TIMP-1 (r = 0.574, p < 0.05) and thickness of the smooth muscle layer (r = 0.499, p < 0.05). Conclusions : This study indicates that CTGF upregulation correlates with MMP-9, probably involved in the pathogenesis of airway remodeling of asthma.

Asthma is a common respiratory disease worldwide. Cytokines play a crucial role in the immune system and the inflammatory response to asthma. Abnormal cytokine expression may lead to the development of asthma, which may contribute to pathologies of this disease. As cytokines exhibit pleiotropy and redundancy characteristics, we summarized them according to their biologic activity in asthma development. We classified cytokines in three stages as follows: Group 1 cytokines for the epithelial environment stage, Group 2 cytokines for the Th2 polarization stage, and Group 3 cytokines for the tissue damage stage. The recent cytokine-targeting therapy for clinical use (anti-cytokine antibody/anti-cytokine receptor antibody) and traditional medicinal herbs (pure compounds, single herb, or natural formula) have been discussed in this review. Studies of the Group 2 anti-cytokine/anti-cytokine receptor therapies are more prominent than the studies of the other two groups. Anti-cytokine antibodies/anti-cytokine receptor antibodies for clinical use can be applied for patients who did not respond to standard treatments. For traditional medicinal herbs, anti-asthmatic bioactive compounds derived from medicinal herbs can be divided into five classes: alkaloids, flavonoids, glycosides, polyphenols, and terpenoids. However, the exact pathways targeted by these natural compounds need to be clarified. Using relevant knowledge to develop more comprehensive strategies may provide appropriate treatment for patients with asthma in the future.

Background and Study Aims. The optimal dose of intravenous proton-pump inhibitor (PPI) therapy for the prevention of peptic ulcer (PU) rebleeding remains controversial. This study aimed to understand the real world experiences in prescribing high-dose PPI and non-high-dose PPI for preventing rebleeding after endoscopic treatment of high-risk PU. Patients and Methods. A total of 220 subjects who received high-dose and non-high-dose pantoprazole for confirmed acute PU bleeding that were successfully treated endoscopically were enrolled. They were divided into rebleeding (n=177) and non-rebleeding groups (n=43). Randomized matching of the treatment-control group was performed. Patients were randomly selected for non-high-dose and high-dose PPI groups (n=44 in each group). Results. Univariate analysis showed, significant variables related to rebleeding were female, higher creatinine levels, and higher Rockall scores (≧6). Before case-control matching, the high-dose PPI group had higher creatinine level, higher percentage of shock at presentation, and higher Rockall scores. After randomized treatment-control matching, no statistical differences were observed for rebleeding rates between the high-dose and non-high-dose groups after case-control matching. Conclusion. This study suggests that intravenous high-dose pantoprazole may not be superior to non-high-dose regimen in reducing rebleeding in high-risk peptic ulcer bleeding after successful endoscopic therapy.