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Background Growing evidence has revealed abnormalities in the retinal structure of patients with alopecia areata (AA). However, the relationship between AA and retinopathy remains unclear. Objective To investigate the association between AA and retinal diseases. Method The study participants were recruited from the National Health Insurance Research Database in Taiwan. We included 9,909 patients with AA and 99,090 matched controls to assess the risk of retinal diseases. A Cox regression model was used for all analyses. Results Compared with the controls, patients with AA had an adjusted hazard ratio (aHR) of 2.96 (95% confidence interval [CI], 2.20–3.98) for retinal diseases. With respect to individual retinal disease, AA patients had a significantly higher risk of developing retinal detachment (aHR, 3.80; 95% CI, 1.97–7.31), retinal vascular occlusion (aHR, 2.14; 95% CI, 1.09–4.19), and retinopathy (aHR 3.18; 95% CI 2.21–4.57) than controls. Limitations This is a retrospective cohort study. Meanwhile, almost all the participating individuals were residents of Taiwan; therefore, the validity of our findings in other demographics remains unclear. Conclusion Patients with AA had a significantly higher risk of retinal disease than the controls. Further studies are needed to clarify the pathophysiology of AA and retinal diseases.

The term Jingluo, translated as meridian or channel, is a core component of traditional Chinese medicine (TCM) and has played a fundamental role in guiding the clinical practice of acupuncture for thousands of years. However, the essence of the meridian remains elusive and is a source of both confusion and debate for researchers. In this study, a “4D” systemic view on the essence of the meridian, namely substantial, functional, chronological, and cultural dimensions, was proposed based on a review of the ancient medical classics, recent research developments, and results from clinical practice. Previous studies have primarily focused on the substantial dimension of the meridian system, with scant interpretation about its functional domain. Neither systemic data nor evaluations have been adequately documented. Additionally, a limited but increasing number of studies have focused on the chronological and cultural dimensions. More investigations that embody the holistic concept of TCM and integrate the systemic modes and advanced techniques with dominant diseases of TCM need to be performed to obtain a more comprehensive understanding of the essence of meridians. The goal of this study is to yield useful information in understanding the essence of meridians and provide a reference and perspective for further research.

Long-chain non-coding RNA ASB16-AS1 has been proven to be an oncogene for many cancer types. However, the relationship between ASB16-AS1 and immunity is still under studied. This study aims to explore the expression and prognostic potential of ASB16-AS1, and to visualize the relationship between ASB16-AS1 expression and immune infiltration in pan-cancer. We clarified ASB16-AS1 expression patterns in pan-cancer and its relationship with prognosis through multi-platform and multi-database sources (TCGA, GEO, GTEx, ArrayExpress, and SRA), and verified the function of ASB16-AS1 in liver hepatocellular carcinoma (LIHC). Then, a variety of immune cell content evaluation methods were used to mutually verify the correlation between ASB16-AS1 and immune infiltration. Finally, the relationships between ASB16-AS1 and some molecular characteristics (immune checkpoints, tumor mutation burden, microsatellite instability, oncogenic signaling pathways) were further explored. In terms of comprehensive analysis, compared with non-tumor tissues, ASB16-AS1 was highly expressed in tumor tissues, and indicated the value of poor prognosis in multiple cancer types. Functional assays, such as CCK8 assay, transwell assay and wound scratch assay, verified that high ASB16-AS1 expression promoted tumor progression in LIHC. ASB16-AS1 was positively correlated with B cells, T cell CD4+ and T cell CD8+ in most cancer types, and negatively correlated with macrophages, dendritic cells and neutrophils in some cancer types, especially in neutrophils. In addition, there were different interaction modes between ASB16-AS1 and molecular features, such as the relationship with oncogenic signaling pathways, showing that the high ASB16-AS1 expression was related to alterations in oncogenic signaling pathways. Our study emphasizes that ASB16-AS1 is a potential pan-cancer prognostic marker, whichs is associated with the immune infiltration in multiple cancer types.

Objective: We investigated the diagnostic progression to bipolar disorder (BD) among adolescents and young adults with attention-deficit/hyperactivity disorder (ADHD). Methods: Using the Taiwan National Health Insurance Research Database, we enrolled adolescents and young adults aged 10–29 years with ADHD between January 1, 2001, and December 31, 2010, who were followed up until December 31, 2011, to determine progression to BD. Cox regression analysis was used to examine candidate risk and protective factors. Results: At the 11-year follow-up, the progression rate from ADHD to BD was 5.12%. Of the participants who progressed, 62.16% (322/518) progressed within the first 3 years. Risk factors for progression were as follows: older age (hazard ratio [HR], 1.058; 95% confidence interval [CI], 1.033–1.084), comorbidity with autistic spectrum disorder (HR, 1.839; 95% CI, 1.415–2.391), disruptive behavior disorder (HR, 1.434; 95% CI, 1.132–1.816), intelligence disability (HR, 1.744; 95% CI, 1.399–2.176), depressive disorder (HR, 1.978; 95% CI, 1.577–2.482), alcohol use disorder (HR, 1.705; 95% CI, 1.057–2.751), cluster A (HR, 2.508; 95% CI, 1.167–5.391) or B (HR, 2.718; 95% CI, 1.974–3.741) personality disorder, and a family history of BD (HR, 2.618; 95% CI, 1.823–3.758) Identified protective factors were male sex (HR, 0.771; 95% CI, 0.630–0.943) and cluster C personality disorder (HR, 0.278; 95% CI, 0.086–0.898). Conclusion: The study demonstrated the specific risk and protective factors for BD progression among adolescents and young adults with ADHD. It is important for clinician and mental health care providers to recognize identified factors to focus on early detection and prompt intervention.

This Taiwan study examined the associations of parental age and mental disorders with the offspring risks of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), major depressive disorder (MDD), and bipolar disorder (BD). Children born between January 1991 and December 2004 in Taiwan were enrolled as the birth cohort (n = 4,138,151) and followed up until December 2011. A logistic regression analysis was performed to identify the odds ratio (OR). The advanced age effects were significant in ADHD (range of OR: 1.04 to 1.49) and ASD (range of OR: 1.35 to 2.27). Teenage mothers, teenage fathers, and fathers ≥ 50 years had higher offspring risks of MDD (range of OR: 1.24 to 1.46); and teenage mothers and fathers ≥ 50 years had increased offspring risks of BD (range of OR: 1.23 to 1.87). Both paternal and maternal mental disorders were associated with higher risks of within-disorder transmission for ADHD, ASD, MDD, and BD (range of OR: 2.64 to 30.41). Besides, parents with one of these four mental disorders (ADHD, ASD, MDD, and BD) might have higher risk of cross-disorder transmission to at least one of the other three mental disorders in the offspring (range of OR: 1.35 to 7.15). Parental age and mental disorders had complex and nuanced patterns in association with offspring mental disorders.

Purpose: Subjects with obstructive sleep apnea (OSA) exhibit systemic and upper airway oxidative stress and inflammation, which cause mitochondrial dysfunction. The intend of this study is to estimate mitochondrial function (mitochondrial DNA/nuclear DNA [Mt/N] ratio) and protein levels of peroxisome proliferator-coactivated receptor gamma co-activator 1-alpha (PGC1-α) in the exhaled breath condensate (EBC) and plasma before and after continuous positive airway pressure (CPAP) treatment. Materials and methods: Twenty healthy individuals (control) and 40 subjects with severe or moderate OSA were recruited to undergo CPAP treatment and evaluation in a sleep study. The Mt/N ratio in the EBC and blood were assayed by quantitative real-time polymerase chain reaction. Enzyme-linked immunosorbent assay was used to measure the protein concentration of PGC1-α in the EBC and plasma. All experiments were performed after 3 months of CPAP treatment in subjects with OSA. Results: We observed no noteworthy differences between the control and treatment groups. Moreover, there were no differences in the Mt/N ratio in the blood and plasma levels of PGC1-α in subjects with OSA before and after treatment. However, the Mt/N ratio and protein levels of PGC1-α in the EBC of OSA subjects were higher than those in the control group and returned to normal levels after CPAP treatment. Conclusions: We successfully treated subjects with OSA by CPAP, which restored the Mt/N ratio and levels of PGC1-α in the EBC.

Background Accumulating evidence suggests neurological manifestations after dengue infection. However, the relationship between dengue and long-term neurocognitive sequel remains unclear. Methods We recruited 816 patients with dengue and 8,160 controls between 1997 and 2012 using data from Taiwan National Health Insurance Research Database and followed them up until the end of 2013. Individuals who exhibited any type of dementia were identified during the follow-up period. Cox regression analyses were performed with adjustments for demographic data and medical and mental comorbidities (cerebrovascular diseases, traumatic brain injury, hypertension, dyslipidemia, diabetes mellitus, depression, alcohol use disorder, and substance use disorder). The E-value for the causality of the evidence was calculated. Sensitivity analysis was conducted to exclude patients with prodromal dementia. Results Patients with dengue were more likely to develop dementia (hazard ratio [HR]: 2.23, 95% confidence interval [CI]: 1.51–3.28), Alzheimer's disease (HR: 3.03, 95% CI: 1.08–8.45), and unspecified dementia (HR: 2.25, 95% CI: 1.43–3.53), but not vascular dementia compared to controls during the follow-up period. Sensitivity analyses after exclusion of the observation period over the first three years or first five years and after exclusion of patients’ enrollment before 2010 or 2008 showed consistent findings. The E-values for the HR (range 3.62–5.51) supported the association between dengue and subsequent dementia among the whole population, men, and women. Conclusion The risk of dementia was 2.23-fold higher in patients diagnosed with dengue during the follow-up period than in the controls. Further studies are necessary to investigate the underlying pathophysiology of dengue and dementia.

Metabolic syndrome (MetS) is associated with cardiovascular diseases, type 2 diabetes, chronic renal diseases, and all-cause mortality. Furthermore, MetS is associated with poor health-related quality of life (HRQOL). However, the impact of dynamic changes in MetS on changes in the HRQOL was not previously explored. This was an eight-year, prospective cohort study in which 906 middle-aged adults from Shipai, Taipei in northern Taiwan were enrolled during 2009–2010 (baseline). Of those sampled, 427 participants completed the follow-up investigation after 8 years. The HRQOL was measured using the Short Form Health Survey (SF-36). Other variables including age, sex, marital status, level of education, smoking, alcohol consumption, baseline body mass index, and changes in physical activity were adjusted. Compared with adults who never experienced MetS, adults with persistent MetS had a negative change in mental HRQOL (β − 4.20, 95% CI − 7.54 to − 0.86, p = 0.01). The negative changes of persistent MetS on the HRQOL were in the domains of vitality and mental health (β − 4.42, 95% CI − 8.10 to − 0.73 and β − 3.47, 95% CI − 6.90 to − 0.04, respectively). Women and overweight adults were vulnerable to the detrimental effects of persistent MetS. For better HRQOL, more resources should be devoted to reversing MetS in public health.

Migraine headaches can be provoked by surgical stress and vasoactive effects of anesthetics of general anesthesia in the perioperative period. However, it is unclear whether general anesthesia increases the migraine risk after major surgery. Incidence and risk factors of postoperative migraine are also largely unknown. We utilized reimbursement claims data of Taiwan’s National Health Insurance and performed propensity score matching analyses to compare the risk of postoperative migraine in patients without migraine initially who underwent general or neuraxial anesthesia. Multivariable logistic regressions were applied to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for migraine risk. A total of 68,131 matched pairs were analyzed. The overall incidence of migraine was 9.82 per 1000 person-years. General anesthesia was not associated with a greater risk of migraine compared with neuraxial anesthesia (aORs: 0.93, 95% CI: 0.80–1.09). This finding was consistent across subgroups of different migraine subtypes, uses of migraine medications, and varying postoperative periods. Influential factors for postoperative migraine were age (aOR: 0.99), sex (male vs. female, aOR: 0.50), pre-existing anxiety disorder (aOR: 2.43) or depressive disorder (aOR: 2.29), concurrent uses of systemic corticosteroids (aOR: 1.45), ephedrine (aOR: 1.45), and theophylline (aOR: 1.40), and number of emergency room visits before surgery. There was no difference in the risk of postoperative migraine between surgical patients undergoing general and neuraxial anesthesia. This study identified the risk factors for postoperative migraine headaches, which may provide an implication in facilitating early diagnoses and treatment.

Background Coronavirus Disease 2019 (COVID-19) spread all over the world in 2020. In the face of the sudden pandemic, workforce mobilization has been of critical concern to medical institutions. During the pandemic, the public's behaviors of seeking medical assistance have also changed. Using the real-world data of a large medical center in Taiwan, this study aimed to analyze the fluctuations of outpatient visits among various departments and divisions in the early phase of the COVID-19 pandemic and to provide suggestions for staff allocation in similar future events. Methods Data of outpatient visits at Taipei Veterans General Hospital were obtained for analysis. The weekly fluctuations of outpatient visits among 36 departments or divisions were computed for the 8 weeks from February 3 to March 29, 2020, the early phase of the pandemic. The monthly data of outpatient visits by department and division in March 2020 were also extracted for comparison with those in March 2019. A simple regression equation was used to calculate the weekly trends. Results Average outpatient visits decreased by 26% in the 2 months following the outbreak. Among the 36 departments or divisions, ophthalmology, orthopedics, and cardiology underwent marked declines after the outbreak; the slopes of the simple regression equation were -110.8, -100.7, and -99.2, respectively. By contrast, transfusion medicine, toxicology, transplantation surgery, pediatric surgery, chest surgery, technical aid, and oncology were divisions less influenced. In the year-over-year comparison, infection was the only department or division with positive growth (20.5%), whereas all others exhibited negative growth. Conclusion In the future, we can fulfil the additional personnel needs during a pandemic by redeploying physicians from departments experiencing a reduced workload. Hospitals should also establish preparatory employee training programs to ensure that the reassigned personnel are adequately equipped to serve in their new positions.

BACKGROUND: Stem cells intra-articular injection stagey indicated a potential therapeutic effect on improving the pathological progress of osteoarthritis (OA). However, the long-term effect of stem cells intra-articular injection on the cartilage regeneration remains unclear. miR-29a-3p is predicted to be a critical target for inhibiting insulin-like growth factor-1 expression and may aggravate the progression of OA. METHODS: In this study, we investigated the therapeutic efficacy of intra-articular injection of bone marrow mesenchymal stem cells (BMSCs) transfected with miR-29a-3p inhibitor in OA. RESULTS: miR-29a-3p inhibitor transfection did not influence cell viability of BMSCs, while the chondrogenic differentiation potential of BMSCs was significantly improved. Interestingly, intra-articular injection of BMSCs with miR-29a-3p inhibition significantly prevented articular cartilage degeneration by up-regulating the expression of Sox 9, Col-2a1, aggrecan and down-regulating the expression of matrix metalloproteinase, as well as relieved pain in OA. CONCLUSION: The double effects on cartilage protection and pain relief indicated a great potential of intra-articular injection of miR-29a-3p inhibitor-transfected BMSCs for the treatment of OA.

To investigate the correlation of platelet and coagulation function with blood stasis syndrome (BSS) in coronary heart disease (CHD). The protocol for this meta-analysis was registered on PROSPERO (CRD42019129452). PubMed, Excerpta Medica Database (Embase), the Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to 1st June, 2020. Trials were considered eligible if they enrolled BSS and non-BSS (NBSS) patients with CHD and provided information on platelet and coagulation function. The platelet function, coagulation function, and fibrinolytic activity were compared between the BSS and NBSS groups. Forest plots were generated to show the SMDs or ESs with corresponding 95% CIs for each study. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity. The systematic search identified 1,583 articles. Thirty trials involving 10,323 patients were included in the meta-analysis. The results showed that mean platelet volume, platelet distribution width, platelet aggregation rate, platelet P selectin, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), thromboxane B2 (TXB2), 6-keto-prostaglandin F1alpha (6-keto-PGF1 α), and TXB2/6-keto-PGF1 α were higher in the BSS group than in the NBSS group (P

BACKGROUND Persistent inflammation induced by viral infection may contribute to the pathogenesis of biliary atresia (BA). Moreover, CD4+ helper cells and CD8+ killer cells are the main effector cells involved in BA and intrahepatic bile duct injuries. OBJECTIVE Thus, we aimed to explore the dynamics of inflammatory cell infiltration and inflammation-regulated pathways in liver-specific inflammatory responses. METHODS Neonatal Balb/C mice were intraperitoneally infected with 1 × 106 PFU rhesus rotavirus (RRV; BA + group), 1 × 105 PFU RRV (BA- group), or DMEM (control group). Mice were sacrificed 7 or 14 days post-infection and their bile ducts, livers, and spleen-derived tissues were examined via H & E staining. The number of CD4+T lymphocytes helper cells (CD4+Th), CD8+T lymphocytes killer cells (CD8+Tc), natural killer (NK) cells, and macrophages (Mac) in the liver and spleen were quantified by flow cytometry. The expression of inflammatory genes was analyzed via a PCR-array. Western blotting was conducted to quantify the protein expression of Notch receptor active fragments (NICD). Finally, some mice were injected with DAPT (a γ-secretase inhibitor) 12 h post-infection followed by analysis of liver and bile duct tissues after 14 days. RESULTS The numbers of CD4+Th cells were increased in the livers of BA- mice after 14 days (P

Background Retrospective studies have suggested that patients with dementia have higher prevalence of atopic dermatitis (AD) than those without dementia. However, the temporal association of AD with subsequent dementia remains unknown. Objective To assess the temporal association of AD with subsequent dementia. Methods We included data of patients with AD aged 45 years and older (n = 1059) and 1:10 age, sex, residence, income, and dementia-related comorbidity–matched controls (n = 10,590) from the Taiwan National Health Insurance Research Database and reviewed their subsequent dementia development from the enrollment date to the end of 2013. Results After adjustments for dementia-related comorbidities, patients with AD were found to be more likely to develop any dementia (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.24-3.29), particularly Alzheimer's disease (HR, 3.74; 95% CI, 1.17-11.97), during the follow-up period than those in the control group. Moderate-to-severe AD was associated with a high subsequent dementia risk (HR, 4.64; 95% CI, 2.58-8.33). Sensitivity analyses with the exclusion of the first 3 (HR, 2.20; 95% CI, 1.28-3.80) or 5 (HR, 2.05; 95% CI, 1.08-3.89) years of observation revealed consistent findings. Conclusion AD may be an independent risk factor for new-onset dementia. Clinicians may monitor the trajectory of neurocognitive function among elderly patients with AD. Additional studies elucidating the pathomechanisms between AD and subsequent dementia are warranted.

Background and Purpose: Patients with obsessive-compulsive disorder (OCD) tend to be comorbid with stroke-related risk factors, including obesity, hypertension, and diabetes. However, the temporal association between OCD and subsequent stroke risk is unclear. Methods: Using data collected between 2001 and 2010 by Taiwan’s National Health Insurance Research Database, 28 064 adult patients with OCD (International Classification of Diseases, Ninth Revision, Clinical Modification [ ICD-9-CM ] code: 300.3) and 28 064 age-, sex-, and comorbidity-matched controls were included in this study. Patients who developed ischemic ( ICD-9-CM codes: 433, 434, and 435) and hemorrhagic ( ICD-9-CM codes: 430, 431, and 432) stroke during follow-up (from enrollment to end of 2011) were identified. Moreover, medications used for treating OCD were assessed. Results: Patients with OCD (hazard ratio [HR], 3.02 [95% CI, 1.91–4.77]), especially middle-aged (HR, 2.66 [95% CI, 1.34–5.29]) and elderly adults (HR, 3.46 [95% CI, 1.70–7.05]), had an elevated risk of developing ischemic stroke during the follow-up period compared with non-OCD controls. The cumulative HR of hemorrhagic stroke did not differ (HR, 0.87 [95% CI, 0.42–1.80]) between the OCD and non-OCD groups. In patients with OCD, both short- (HR, 1.69 [95% CI, 0.74–3.88]; HR, 0.31 [95% CI, 0.05–1.95]) and long-term use (HR, 1.37 [95% CI, 0.60–3.16]; HR, 0.90 [95% CI, 0.22–3.76]) of OCD medications were not correlated with ischemic and hemorrhagic stroke compared with nonuse. Conclusions: Clinicians should closely monitor cerebrovascular disease and related risks in patients with OCD. The pathomechanism of OCD with an increased risk of ischemic stroke warrants further investigation.

A new isocoumarin, penicimarin N (1), along with five known compounds (2-6), were isolated from the mangrove-derived fungus Penicillium sp. TGM112. The structure of 1 was elucidated on the basis of extensive spectroscopic data analysis, and the absolute configuration of 1 was determined by comparison of their circular dichroism (CD) spectra with the literature. The structures of known compounds were determined by comparison with the literature data. All the isolated compounds were examined for their antioxidant and α-glucosidase activities. Compound 1 showed strong antioxidant activity with the IC50 value of 1.0 mM, and 1 also exhibited moderate inhibitory activity against α-glucosidase with the IC50 value of 620 μM.

Psoriasis has been associated with the risk of several ocular complications; however, its relationship with retinal diseases remains unknown. This study aimed to investigate the risk of developing retinal diseases in patients with psoriasis. Study participants were recruited from the National Health Insurance Research Database in Taiwan. A total of 11 729 psoriasis patients and 117 290 matched controls were included, showing an incidence rate of 121.15 and 28.34 cases of retinal diseases per 100 000 person-years, respectively. Compared with controls, patients with psoriasis had an adjusted hazard ratio (aHR) of 3.40 (95% confidence interval [CI], 2.63-4.39) for retinal diseases after adjustment for potential confounders. Regarding the individual retinal disease, psoriasis patients had a significantly higher risk of developing retinal detachment (aHR, 5.07; 95% CI, 2.92-8.79), retinal vascular occlusion (aHR, 3.75; 95% CI 2.42-5.82), and retinopathy (aHR, 2.84; 95% CI, 1.99-4.05) than controls. In conclusion, patients with psoriasis had a significantly higher risk of retinal diseases than controls. Further studies are necessary to investigate the pathophysiology underlying the relationship between psoriasis and retinal diseases.

BACKGROUND: In early 2020, a global outbreak of 2019 novel coronavirus disease (COVID-19) caused high mortality rates and public panic. Worldwide demand for personal protective equipment has risen, with diminishing supplies and shortages reported. During the pandemic, charitable donations have been made by the public, aimed at helping medical staff. Based on the open data, we investigate the charitable in-kind donations received by a large medical center in northern Taiwan (Taipei Veterans General Hospital [TPEVGH]) in Taiwan during the pandemic. METHODS: The period of investigation was the first half of the year 2020. TPEVGH has received various public donations. The list of donations published on the hospital's official website was analyzed. The variables in the analysis were donation category, donation percentage, number of donations, and total donation amount. RESULTS: Most in-kind donations were food and beverages (55.1%), with a monetary value of 3 124 510 New Taiwan Dollars (NTD) (24.3%). Medical equipment accounted for the second-highest number of items (34.8%) but was the highest monetary value (70.6%; 9 275 945 of 12 875 855 NTD). Daily necessities accounted for the lowest number of items (10.1%) and had a total monetary value of 475 400 NTD (3.7%). Over two-thirds were beverages (68.4%), all of which were bottles or cans for easy storage. Despite only five items (13.2%) being juice, the donation size was the largest, accounting for nearly half (47.1%) of the total monetary value. Only one item was fruit, which was high-class organic apples. The monetary value of this item was the highest (7.8%) among all donated food. Most donated snacks were biscuits. CONCLUSION: During the COVID-19 pandemic, most public donations to TPEVGH were food and daily necessities. While every donation should be appreciated, accepting high volumes of donations might incur donation management problems. Further research could be focused on managerial aspects, for example, quality and safety checking, storage, and distribution.

Background Hepatic steatosis is a big hurdle to treat type 2 diabetes (T2D). Fasting-mimicking diet (FMD) has been shown to be an effective intervention in dyslipidemia of T2D. However, fasting may impair the normal glucose metabolism. Human umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation has been discovered to regulate immune reactions and reduce hyperglycemia in diabetes. However, the effect of UC-MSCs on improving the lipid metabolism disorder is not quite satisfactory. We have investigated the efficacy comparison and interaction between FMD and UC-MSC infusion, aiming to establish effective T2D therapies and explore its mechanism. Methods C57/BL6 mice were fed with high-fat diet (HFD) to induce a diet-induced obese (DIO) mouse model. Leptin receptor-deficient (db/db) mice were used for follow-up experiments. DIO or db/db mice were divided into 4 groups: phosphate buffer saline (PBS), UC-MSCs, FMD, and UC-MSCs + FMD. At the end of the study period, mice were fasted and sacrificed, with the measurement of physiological and biochemical indexes. In addition, the fresh liver, skin, and white adipose tissue were analyzed by histology. Results FMD restored the lipid metabolism in DIO mice, whereas its capacity to rescue hyperglycemia was uncertain. Infusion of UC-MSCs was effective in T2D glycemic control but the impact on dyslipidemia was insufficient. Furthermore, both the glucose and the lipid alterations of DIO and db/db mice recovered after UC-MSCs combined with FMD. It was proved that UC-MSCs promoted FMD effects on ameliorating hyperglycemia and restoring the lipid metabolism in T2D mice, while FMD had little promotion effect on UC-MSCs. Mechanistically, we discovered that UC-MSC infusion significantly modulated systematic inflammatory microenvironment, which contributed to concerted actions with FMD. Conclusions We established a strategy that combined UC-MSC infusion and FMD and was effective in treating T2D, which provided potential approaches for developing novel clinical T2D therapies.

Background This study aimed to assess the use of medical record items in clinical research in one large academic medical center in Taiwan. Methods A descriptive survey design was adopted to collect the data. Articles published in 2018 by Taipei Veterans General Hospital (TVGH) staff as the first author were obtained. The types of specialties and types of research were analyzed. To understand the conditions for the use of medical records, the retrospective research using hospital's medical records were analyzed. Each article was read in entirety to realize the use and number of patients and the medical record items. Results Among the 362 articles first-authored by TVGH staff in 2018, 219 (60.4%) were classified as clinical studies, 60 (16.6%) as basic studies, 53 (14.6%) as database studies, and 30 (8.2%) as other categories. About 50% of the retrospective research using TVGH medical records had a case number less than 100 (67 cases, 49.6%) with an average number of 41 cases and 13 studies (9.6%) had a case number greater than 1000. Analysis of the number of medical record items used in 135 retrospective research studies based on TVGH medical records showed that 118 (87.4%) used basic patient information. In addition to basic information, notes written by professionals were used most frequently (73 cases, 54.0%), whereas medication information was used in 50 cases (37.0%); laboratory test data was used in 49 cases (36.2%) ; and body measurements was used in 27 cases (20%). Conclusion More than one-third of publications utilized medical records, but the patient numbers and record items in use were relatively limited. In the era of digitalization and big data analytics, the potential of medical records in research deserves attention. Investment in establishing a more accessible database of medical records to access nonstructural, descriptive medical records could be considered.

Background:. Andersson lesions (ALs) are not uncommon in ankylosing spondylitis (AS). Plain radiography (PR) is widely used for the diagnosis of ALs. However, in our practice, there were some ALs in AS patients that could not be detected on plain radiographs. This study aimed to propose the concept of occult ALs and evaluate the prevalence and radiographic characteristics of the occult ALs in AS patients. Methods:. A total of 496 consecutive AS patients were admitted in the Affiliated Drum Tower Hospital, Medical School of Nanjing University between April 2003 and November 2019 and they were retrospectively reviewed. The AS patients with ALs who met the following criteria were included for the investigation of occult ALs: (1) with pre-operative plain radiographs of the whole-spine and (2) availability of pre-operative computed tomography (CT) and/or magnetic resonance imaging (MRI) of the whole-spine. The occult ALs were defined as the ALs which were undetectable on plain radiographs but could be detected by CT and/or MRI. The extensive ALs involved the whole discovertebral junction or manifested as destructive lesions throughout the vertebral body. Independent-samples t test was used to compare the age between the patients with only occult ALs and those with only detectable ALs. Chi-square or Fisher exact test was applied to compare the types, distribution, and radiographic characteristics between detectable and occult ALs as appropriate. Results:. Ninety-two AS patients with a mean age of 44.4 ± 10.1 years were included for the investigation of occult ALs. Twenty-three patients had occult ALs and the incidence was 25% (23/92). Fifteen extensive ALs were occult, and the proportion of extensive ALs was significantly higher in detectable ALs (97% vs. 44%, χ2 = 43.66, P

Background The effect of relative age on the diagnoses of attention deficit hyperactivity disorder (ADHD), disruptive behavior disorder (DD), anxiety disorder, and depressive disorder and the prescription for ADHD and antidepressant medications remains unclear. Aim To clarify the impact of relative age in a school year with the diagnoses of ADHD, DD, anxiety disorder and depressive disorder and the prescription for ADHD and antidepressant medications. Methods The annual cutoff birthdate for entry to school in Taiwan is August 31. The Taiwan National Health Insurance Research Database was used to enroll 9,548,393 children and adolescents aged 3-17 years during the study period (September 1, 2001, to August 31, 2011). The poisson regression model was performed to examine the likelihood of receiving diagnoses of ADHD, DD, anxiety disorder, and depressive disorder, as well as the prescription of ADHD and antidepressant medications among children born in August (the youngest) and September (the oldest). Results Both boys and girls born in August had a higher risk of being diagnosed as having ADHD (odds ratio [OR] = boys: 1.65, girls: 1.80), DD (1.29, 1.45), anxiety disorder (1.49, 1.33), and depressive disorder (1.10, 1.10). Furthermore, children born in August were more likely to be prescribed ADHD medication (1.71, 1.72) and antidepressants (1.18, 1.09) compared with those born in September. Discussion Relative age, as an indicator of neurocognitive maturity, is a critical factor for the likelihood of being diagnosed as having ADHD, DD, anxiety disorder, and depressive disorder among children and adolescents.

AimsTo identify single-nucleotide polymorphisms (SNPs) associated with central serous chorioretinopathy (CSCR) by a systematic review and meta-analysis, and to compare the association profiles between CSCR, neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).MethodsWe searched the EMBASE, PubMed and Web of Science for genetic studies of CSCR from the starting dates of the databases to 12 September 2020. We then performed meta-analyses on all SNPs reported by more than two studies and calculated the pooled OR and 95% CIs. We also conducted sensitivity analysis and adopted the funnel plot to assess potential publication bias.ResultsTotally 415 publications were reviewed, among them 10 were eligible for meta-analysis. We found 10 SNPs that have been reported at least twice. Meta-analysis and sensitivity analysis confirmed significant associations between CSCR and six SNPs in three genes, namely age-related maculopathy susceptibility 2 (ARMS2) (rs10490924, OR=1.37; p=0.00064), complement factor H (CFH) (rs800292, OR=1.44; p=7.80×10−5; rs1061170, OR=1.34; p=0.0028; rs1329428, OR=1.40; p=0.012; and rs2284664, OR=1.36; p=0.0089) and tumour necrosis factor receptor superfamily, member 10a (TNFRSF10A) (rs13278062, OR=1.34; p=1.44×10−15). Among them, onlyTNFRSF10Ars13278062 showed the same trend of effect on CSCR, nAMD and PCV, while the SNPs inARMS2andCFHshowed opposite trends in the SNP associations.ConclusionsThis study confirmed the associations ofARMS2,CFHandTNFRSF10Awith CSCR, and revealed thatARMS2,CFHandTNFRSF10Amay affect different phenotypic expressions of CSCR, nAMD and PCV.

The annual cut-off birthdate for entry into school in Taiwan is August 31. Thus, children and adolescents born in August are typically the youngest in their grades. The potential effect of relative age on the diagnosis of autism spectrum disorder (ASD) remains uncertain. A total of 9,548,393 individuals aged 3–17 years during the study period (from September 1, 2001, to August 31, 2011) identified from the Taiwan National Health Insurance Research Database were enrolled into our study. Logistic regression analysis was used to examine the likelihood of receiving ASD diagnosis for those who were born in August (the youngest) compared with those who were born in September (the oldest). Both boys and girls born in August had a higher likelihood of being diagnosed with ASD (odds ratio [OR]: 1.24, 95% confidence interval [CI]: 1.16–1.32; OR: 1.23, 95% CI 1.06–1.42) than did those born in September. Sensitivity analysis conducted over different periods revealed consistent findings. Relative age, as an indicator of neurocognitive maturity, is a crucial contributor to the risk of being diagnosed with ASD among children and adolescents. Our findings highlight the importance of considering the age of a child within a grade when diagnosing ASD.

Osteosarcoma is a malignant tumor with high mortality in children and adolescents. The mechanism of osteosarcoma metastasis is currently unclear. Abnormal expression of long non-coding RNA (lncRNA) plays an important role in tumor metastasis. We used bioinformatics to analyze the differences in gene expression between osteosarcoma in situ and osteosarcoma lung metastases. CCK-8 was used to detect the effect of lncRNA LOC100129620 on the proliferation of osteosarcoma cells. The effect of LOC100129620 on the invasion of osteosarcoma cells was assessed by Transwell assay. The regulatory effect of LOC100129620 on miR-335-3p was examined using RNA pull-down and luciferase reporter gene assays. The effect of LOC100129620 on the polarization of macrophages was detected by quantitative real-time fluorescent PCR. The results show that LOC100129620 can promote the proliferation and migration of osteosarcoma cells. LOC100129620 can promote the proliferation of osteosarcoma in vivo. LOC100129620 can bind to miR-335-3p and regulate its function. MiR-335-3p mediates the regulatory effects of LOC100129620 on CDK6. LOC100129620 promotes the formation of blood vessels and the polarization of macrophages. The LOC100129620/miR-335-3p/CDK6 signaling pathway promotes the metastasis of osteosarcoma by regulating the proliferation of osteosarcoma cells, angiogenesis, and macrophage polarization.

The coronavirus disease 2019 (COVID-19) has been spreading worldwide, posing a significant threat to human health. Currently, vaccines are available, but there is still no reliable cure for this disease. Traditional Chinese Medicine (TCM) has played an important role in addressing this epidemic, and several clinical studies have emerged regarding treatments for COVID-19 by TCM; status of those treatments, and patterns regarding these are worth summarizing and interpreting systematically. A comprehensive search of clinical trials was performed in various platforms, including PubMed, Embase, Web of Science, medRxiv, China National Knowledge Infrastructure, WanFang Data, and SinoMed, from January 1, 2020 to March 1, 2021. Analyzed information included language, received date, quantity, citations, affiliation, number of authors, research type (randomized controlled trial or non-randomized controlled trial), trial registry information, disease severity, sample size, specific interventions, outcomes, and adverse reactions, among others. Based on the aforementioned information, a quantitative and qualitative literature analysis was done. A total of 47 articles were retrieved, most of which were published in Chinese (42 articles, 89.36%). Based on the results of the number of trial registrations (12 articles), the number of citations (the maximum for a single article was 62), and the modified Chalmers scale (total: 100 points, average: 61.40 points), the overall study quality still needs improvement. Most patients presented with the mild and common type of COVID-19 and were recruited in Hubei Province, while researchers from these studies were from all over the country (135 institutions). TCM interventions included 66 different formulas and 134 herbs, of which Armeniacae semen amarum (Kuxingren), Agastache rugosa (Huoxiang), Ephedra sinica stapf (Mahuang), Gypsum fibrosum (Shigao), Glycyrrhizae radix et rhizome (Gancao), and Gtractylodes rhizoma (Cangzhu) appeared at high frequencies. Highlighted outcomes from these studies included the following: Clinical symptoms (fever, cough, fatigue, etc.), progression rate from normal stage to heavy stage, laboratory indices including leukocyte and lymphocyte counts, and c-reactive protein levels, imaging diversity of lung computed tomography (CT), and recorded adverse reactions. With a certain number of published clinical trials, the landscape of TCM clinical trials for COVID-19 was established. Most studies have a relatively low quality and impact, and standardized implementation of evidence-based research in TCM was lacking. The mainstay TCM treatment for COVID-19 involved clearing heat, releasing the exterior, and resolving its dampness. Additionally, the Maxing Shigan Decoction was one of the most common classical prescriptions for COVID-19, and the “three drugs and three perceptions” were also widely used. Some symptoms, laboratory indicators, and imaging diversity of lung CT were found to have significantly improved after taking these decoctions. Overall, TCM is safe, and no serious adverse reactions have been reported. Through multiple mechanisms, TCM has shown great clinical effects, but its underlying mechanisms and patterns should be further explored. It is of great practical significance to enhance the level of clinical and evidence-based research for TCM application in the prevention and treatment of acute and emergent infectious diseases. Furthermore, such research will help strengthen clinical expertise in this field and further standardize the implementation of evidence-based TCM medical research.

Periodontal disease is prevalent in patients with chronic kidney disease (CKD) and potentially associated with kidney function decline. However, it is uncertain whether periodontal disease affects the risk of mortality and morbidity in patients with advanced CKD. Taiwan’s National Health Insurance Research Database was used to conduct a nationwide population-based cohort study. Propensity score matching procedures were performed to select people with stage 5 CKD and to compare the long-term risk of mortality, end-stage renal disease, and major adverse cardiovascular events (MACE) between people with and without periodontal disease. Multivariable Cox regression analyses were conducted to calculate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the outcome of interest. A total of 8119 subjects with stage 5 CKD were initially included. After matching to demographic and clinical covariates, 1254 subjects with 7099 person-years of follow-up were selected for analyses. Periodontal disease was not associated with long-term risks of all-cause mortality (aHR: 0.77, 95% CI: 0.49–1.22), progression to end-stage renal disease (aHR: 0.91, 95% CI: 0.75–1.10), or MACE (aHR: 1.18, 95% CI: 0.91–1.53). These findings were generally consistent across subgroups of age, sex, comorbid diabetes, uses of systemic antibiotic, and different dental procedures. Periodontal disease is not a predictor for long-term mortality or morbidity in patients with advanced CKD. These results provide important evidence to elucidate the relationship between periodontitis and critical clinical outcomes of advanced CKD.

Type 2 diabetes mellitus (T2DM) is a major threat to global public health, with increasing prevalence as well as high morbidity and mortality, to which immune dysfunction has been recognized as a crucial contributor. Mesenchymal stromal cells (MSCs), obtained from various sources and possessing potent immunomodulatory abilities, have displayed great therapeutic potential for T2DM. Interestingly, the immunomodulatory capabilities of MSCs are endowed and plastic. Among the multiple mechanisms involved in MSC-mediated immune regulation, the paracrine effects of MSCs have attracted much attention. Of note, extracellular vesicles (EVs), an important component of MSC secretome, have emerged as pivotal mediators of their immunoregulatory effects. Particularly, the necrobiology of MSCs, especially apoptosis, has recently been revealed to affect their immunomodulatory functions in vivo. In specific, a variety of preclinical studies have demonstrated the beneficial effects of MSCs on improving islet function and ameliorating insulin resistance. More importantly, clinical trials have further uncovered the therapeutic potential of MSCs for T2DM. In this review, we outline current knowledge regarding the plasticity and underlying mechanisms of MSC-mediated immune modulation, focusing on the paracrine effects. We also summarize the applications of MSC-based therapies for T2DM in both preclinical studies and clinical trials, with particular emphasis on the modulation of immune system.

Study Design: A retrospective study. Objective: To investigate the effect of pedicle subtraction osteotomy (PSO) level on the surgical outcomes in ankylosing spondylitis-related thoracolumbar kyphosis with the same curve pattern. Methods: ankylosing spondylitis (AS) patients with thoracolumbar kyphosis, who underwent 1-level lumbar PSO between March 2006 and June 2017, were retrospectively reviewed. Criteria for curve-matched thoracolumbar kyphosis were: (1) have same level of preoperative apex (pre-apex); (2) have similar global kyphosis (GK, the angle between the superior/inferior endplate of the maximally tilted upper and lower end vertebra) (the difference of GK less than 15˚). The radiographic parameters measured were sagittal vertical axis (SVA, the horizontal distance between the C7 plumb line and the posterosuperior corner of the S1), GK, thoracic kyphosis (TK, the angle between the T5 superior endplate and the T12 inferior endplate), lumbar lordosis (LL, the angle between the L1 and S1 superior endplate), sacral slope (SS, the angle between the sacral endplate and the horizontal line), pelvic tilt (PT, the angle between the vertical and the line joining the midpoint of the sacral plate and hip axis), and pelvic incidence (PI, the angle between the line vertical to the superior margin of S1 and the line connecting the sacral plate midpoint with the hip joint axis). All of these parameters and health-related quality of life (HRQoL, evaluated by preoperative and the last follow-up questionnaires including ODI and VAS) scores were collected before surgery and at the last follow-up. According to their osteotomy level, patients were devided into 2 sub-groups (L1 group and L2 group), and differences of these mentioned parameters between 2 groups were compared. Results: 26 curve-matched patients were recruited with a mean follow-up of 37.2 months. All patients improved significantly after surgery in HRQoL scores (VAS 1.6 vs 5.4, P < 0.001; ODI 11.9 vs 26.4, P < 0.001). Except for TK and PI, those radiographic parameters were also observed to be significantly changed after surgery. Compared to L2 group, PSO at L1 may have larger correction of TK (ΔTK -6.8 vs -0.3°, P = 0.164), PI (ΔPI -7.4 vs -0.7°, P = 0.364) and smaller correction of SVA (ΔSVA -105.3 vs -128.5 mm, P = 0.096), LL (ΔLL -31.1 vs -43.0°, P = 0.307) and SS (ΔSS 6.9 vs 12.2°, P = 0.279) but had no statistical significance. Conclusion: The results of this investigation showed that in AS-related thoracolumbar kyphosis patients with the same curve pattern, the different levels of osteotomy had little effect on the improvement of surgical outcomes. However, osteotomy at L2 is more likely to obtain a larger correction of SVA compared to osteotomy at L1.

BACKGROUND This study aimed to evaluate the differences in nurses' willingness to discuss palliative care with terminally ill patients and their family members. METHODS The participants were randomly recruited from registered staff nurses ≥20 years of age who were responsible for clinical inpatient care in a tertiary hospital in northern Taiwan. A semi-structured questionnaire was administered to evaluate nurses' experiences of discussing do-not-resuscitate (DNR) decisions and their willingness to discuss palliative care with terminal patients and their family members. The differences in nurses' experiences regarding DNR and willingness to discuss palliative care with terminally ill patients and their family members were compared using the Chi-square test. Logistic regressions were used to analyze factors associated with nurses' willingness to discuss palliative care with patients and their families. RESULTS More participants had experienced initiating discussions about DNR with patients' families than with patients (72.2% vs 61.9%, p < 0.001). Unadjusted logistic regression analysis showed that the experiences of actively initiating DNR discussions with patients were a significant factor associated with palliative care discussion with patients (odds ratio [OR] = 2.91, 95% confidence interval [CI]: 1.09-7.79). On the other hand, the experiences of actively initiating DNR discussions with patients and with patients' families were significant factors associated with palliative care discussion with patients' families (OR = 3.84, 95% CI: 1.22-12.06 and OR = 3.60, 95% CI: 1.19-10.90, respectively). After adjusting for covariates, no significant factors were found to be independently associated with nurses' willingness to discuss palliative care with patients and their family members. CONCLUSION There are significant differences in nurses' willingness to discuss palliative care with patients and their family members. Further research is needed to evaluate factors associated with nurses' willingness to discuss palliative care with patients and their families to facilitate these discussions and protect patients' autonomy.

In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.

Objective Posttraumatic stress disorder (PTSD) is known as a risk factor for various immune-related disorders; however, the association between PTSD and related autoimmune skin diseases (ASDs) remains unclear. This study aimed to investigate the association of PTSD with the risk of related ASDs. Methods Participants were recruited from the National Health Insurance Research Database in Taiwan. We included 9801 patients with PTSD and 39,204 matched controls to assess the risk of developing ASDs. Cox regression model was used for analyses. Results After adjusting for confounders, we found an increased risk of ASDs among the patients with PTSD (adjusted hazard ratio [aHR] = 3.00, 95% confidence interval [CI] = 2.21-4.07) compared with that among matched controls. Statistically significant associations were found between PTSD and five individual ASDs, including psoriasis (aHR = 3.81, 95% CI = 1.90-7.67), lichen planus (aHR = 31.63, 95% CI = 4.00-249.91), alopecia areata (aHR = 4.77, 95% CI = 2.47-9.20), autoimmune bullous diseases (aHR = 9.55, 95% CI = 1.98-45.99), and vitiligo (aHR = 16.06, 95% CI = 4.48-57.54). Conclusions Patients with PTSD had an increased risk of developing ASDs compared with the matched controls. Further studies are needed for better understanding of the underlying mechanisms.