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Transmitted drug resistance (TDR) is a critical ongoing public health challenge in HIV/AIDS therapy. We explore the prevalence of TDR, its patterns, its associated risk factors, and predicted drug sensitivity in Beijing between 2015 and 2018.Retrospective data on TDR from 3265 antiretroviral therapy (ART)-naïve patients were collected at Beijing Ditan Hospital from 1 August 2014 to 31 July 2018. TDR was defined according to the Stanford Drug Resistance Mutations Database. TDR prevalence, pattern, risk factors, and predicted drug sensitivity were analysed.The overall prevalence of HIV-1 TDR was 6.68% (218 of 3265), including 0.77%, 3.64%, and 2.36% resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), and protease inhibitors, respectively. The thymidine analogue mutations (TAMs) M41L/LM (4, 0.12%) and non-TAMs mutations M184V/MV/MI (8; 0.24%) were the primary NRTI-associated resistance mutations. K103N/KN (NNRTI associated) and M46L/I/IMV/IM/ML (protease inhibitor associated) were the other major resistance mutations. Patients 40-59 years old who had the CRF08_BC subtype were identified as having higher risk for drug resistance mutation.The prevalence of TDR among ART-naïve individuals with HIV-1 in Beijing was at a moderate level. Long-time and continuous surveillance of HIV TDR is necessary step in the therapy of ART-naive patients.

Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs).A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure.In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003).This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.

Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs).A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool.In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07-1.26, P 0.001), serious infection (Peto OR: 1.65, 95% CI: 1.26-2.17, P 0.001), upper respiratory tract infection (URTI) (Peto OR: 1.17, 95% CI: 1.04-1.32, P = 0.008), nasopharyngitis (Peto OR: 1.25, 95% CI: 1.10-1.42, P 0.001), and Candida infection (Peto OR: 2.64, 95% CI: 1.48-4.71, P = 0.001) were increased in SpA patients treated with biologics compared with placebo. Sensitivity analysis based on biologics classes was conducted, and results demonstrated that compared with placebo, there was a higher risk of infection for tumor necrosis factor (TNF)-a inhibitors (Peto OR: 1.38, 95% CI: 1.13-1.68, P = 0.001) and interleukin (IL)-17 inhibitors (Peto OR: 1.55, 95% CI: 1.08-2.22, P = 0.018) in axial SpA, and for Janus kinase inhibitors in peripheral SpA (Peto OR: 1.39, 95% CI: 1.14-1.69, P = 0.001); higher risk of serious infection for IL-17 inhibitors in peripheral SpA (Peto OR: 3.46, 95% CI: 1.26-9.55, P = 0.016) and axial SpA (Peto OR: 2.01, 95% CI: 1.38-2.91, P 0.001); higher risk of URTI for TNF-a inhibitors in axial SpA (Peto OR: 1.37, 95% CI: 1.05-1.78, P = 0.019), and for apremilast in peripheral SpA (Peto OR: 1.60, 95% CI: 1.08-2.36, P = 0.018); higher risk of nasopharyngitis for TNF-a inhibitors in axial SpA (Peto OR: 1.41, 95% CI: 1.05-1.90, P = 0.022) and peripheral SpA (Peto OR: 1.49, 95% CI: 1.09-2.05, P = 0.013), and for IL-17 inhibitors in axial SpA (Peto OR: 1.35, 95% CI: 1.01-1.82, P = 0.044); higher risk of herpes zoster for Janus kinase inhibitors in peripheral SpA (Peto OR: 2.18, 95% CI: 1.03-4.62, P = 0.043); higher risk of Candida infection for IL-17 inhibitors in peripheral SpA (Peto OR: 2.52, 95% CI: 1.31-4.84, P = 0.006).This meta-analysis shows that biological therapy in patients with SpA may increase the risk of infections, including serious infections, URTI, nasopharyngitis, and Candida infection, which should be paid attention to in our clinical practice.

Persistent immune activation, which occurs during the whole course of HIV infection, plays a pivotal role in CD4

Although extensive use of antiretroviral therapy (ART) has made great progress in controlling HIV replication and improving CD4+ T cell recovery, the immune reconstitution remained insufficient in some patients, who were defined as poor immunological responders (PIRs). These PIRs were at a high risk of AIDS-related and non-AIDS complications, resulting in higher morbidity and mortality rate. Thus, it is a major challenge and urgently needed to distinguish PIRs early and improve their immune function in time. Immune activation is a key factor that leads to impaired immune reconstitution in people living with HIV (PLWH) who are receiving effective ART. Double negative T cells (DNT) were reported to associate with the control of immune activation during HIV infection. However, the precise mechanisms by which DNT cells exerted their suppressive capacity during HIV infection remained puzzled. CD73, both a soluble and a membrane-bound form, display immunosuppressive effects through producing adenosine (ADO). Thus, whether DNT cells expressed CD73 and mediated immune suppression through CD73-ADO pathway needs to be investigated. Here, we found a significant downregulation of CD73 expression on DNT cells in treatment-naïve PLWH (TNs) compared to healthy controls, accompanied with increased concentration of sCD73 in plasma. Both the frequency of CD73+ DNT cells and the level of plasma sCD73 recovered after ART treatment. However, PIRs showed decreased percentage of CD73+ DNT cells compared to immunological responders (IRs). The frequency of CD73+ DNT cells was positively correlated with CD4+ T cell count and CD4/CD8 ratio, and negatively correlated with immune activation in PLWH. The level of sCD73 also showed a negative correlation to CD4+ T cell count and CD4/CD8 ratio. More importantly, in the present cohort, a higher level of sCD73 at the time of initiating ART could predict poor immune reconstitution in PLWH after long-term ART. Our findings highlighted the importance of CD73+ DNT cells and sCD73 in the disease progression and immune reconstitution of PLWH, and provided evidences for sCD73 as a potential biomarker of predicting immune recovery.

IntroductionThe aim of this prospective study is to evaluate the effects of combining topical airway anaesthesia with intravenous induction on haemodynamic variables during the induction period in patients undergoing cardiac surgery.Methods and analysisThis randomised, double-blind, controlled, parallel-group, superiority study from 1 March 2021 to 31 December 2021 will include 96 participants scheduled for cardiac surgery. Participants will be screened into three blocks (ASA II, ASA III, ASA IV) according to the American Society of Anesthesiologists (ASA) grade and then randomly allocated into two groups within the block in a 1:1 ratio. Concealment of allocation will be maintained using opaque, sealed envelopes generated by a nurse according to a computer-generated randomisation schedule. In addition to general intravenous anaesthetics, participants will receive supraglottic and subglottic topical anaesthesia. Changes in arterial blood pressure and heart rate in both groups will be recorded by an independent investigator at the start of anaesthesia induction until the skin incision. If vasopressors are used during this period, the frequency, dosage and types of vasopressors will be recorded. The incidence and severity of participants’ postoperative hoarseness and sore throat will also be assessed.Ethics and disseminationThis study was approved by the Ethics Committee of Qianfoshan Hospital of Shandong Province (registration number: YXLL-KY-2021(003)). The results will be disseminated through a peer-reviewed publication and in conferences or congresses.Trial registration numberNCT04744480.

Key Points: Question: Can the traditional Chinese version of the hearing handicap inventory for elderly screening (HHIE-S) checklist screen for age-related hearing loss (ARHL) in elderly individuals? Findings: In this cross-sectional study of 1696 Taiwanese patients who underwent annual government-funded geriatric health checkups, the Chinese version of the HHIE-S had a sensitivity of 76.9% and a specificity of 79.8% with a cutoff score greater than 6 for identifying patients with disabled hearing loss (defined as a PTA > 40 dB). Meaning: The traditional Chinese version of the HHIE-S is an effective test to detect ARHL and can improve the feasibility of large-scale hearing screening among elderly individuals. Purpose: The traditional Chinese version of the hearing handicap inventory for elderly screening (TC-HHIE-S) was translated from English and is intended for use with people whose native language is traditional Chinese, but its effectiveness and diagnostic performance are still unclear. The purpose of this study was to evaluate the validity and reliability of the traditional Chinese version of the HHIE-S for screening for age-related hearing loss (ARHL). Methods: A total of 1696 elderly people underwent the government’s annual geriatric medical examination at community hospitals. In this cross-sectional study, we recorded average conducted pure-tone averages (PTA) (0.5 kHz, 1 kHz, 2 kHz, 4 kHz), age, sex, and HHIE-S data. Receiver operating characteristic (ROC) curve analysis was used to identify the best critical point for detecting hearing impairment, and the validity of the structure was verified by the agreement between the TC-HHIE-S and PTA results. Results: The HHIE-S scores were correlated with the better-ear pure-tone threshold averages (PTAs) at 0.5–4 kHz (correlation coefficient r = 0.45). The internal consistency of the total HHIE-S score was excellent (Cronbach’s alpha = 0.901), and the test-retest reliability was also excellent (Spearman’s correlation coefficient = 0.60, intraclass correlation coefficient = 0.75). In detecting disabled hearing loss (i.e., PTA at 0.5–4 kHz > 40 dB), the HHIE-S cutoff score of > 6 had a sensitivity of 76.9% and a specificity of 79.8%. Conclusions: The traditional Chinese version of the HHIE-S is a valid, reliable, and efficient tool for large-scale screening for ARHL.

The study objective was to evaluate the association between cervical spondylosis (CS) and a subsequent diagnosis of obstructive sleep apnea (OSA) in light of the expected constricting impact of CS-associated cervical spine changes on the pharyngeal airway space, a key contributor to OSA.Data were retrieved from the Taiwan National Health Insurance Research Dataset. A total of 98,234 patients who newly received a diagnosis of OSA were identified. We identified four propensity score-matched controls per OSA patient (n = 392,936). Chi-square tests were used to compare cases and controls on sociodemographic characteristics, and multivariable logistic regression modelling to examine the association of OSA with prior CS.Of the 98,234 sampled patients, 18,070 (18.4%) patients had a prior CS diagnosis, significantly different among cases compared to controls, being 18.4% and12.1%, respectively, p 0.001. Logistic regression analysis showed an adjusted odds ratio (OR) of prior CS of 1.778 (95% confident interval (CI): 1.744-1.814) relative to controls. The adjusted odds of prior CS without myelopathy was 1.764 for cases relative to controls (95% CI: 1.727-1.801), and for prior CS with myelopathy (adjusted OR: 1.778, 95% CI: 1.721-1.837). Analysis stratified by age showed that in the 45-64- and64-year age groups, the adjusted ORs of CS were 1.803 (95% CI: 1.758-1.850) and 1.634 (95% CI: 1.568-1.703), respectively, for cases relative to controls.Our results suggest that OSA is associated with prior CS. The results call for professionals to be alert to the possibility of subsequent development of OSA among patients with CS.

Chronic human immunodeficiency virus (HIV) infection not only causes a gradual loss of CD4+ T cells but also leads to a disturbance of the T cell receptor (TCR) repertoire. In people living with HIV (PLWH), monitoring TCR repertoire is challenged by the inconsistency of complementarity determining region 3 (CDR3) and limited cell numbers in clinical samples. Thus, a quantitative method is necessary for monitoring the TCR repertoire in PLWH. We characterized the TCR V-J pairing profile of naïve and memory CD4+ T cells in healthy donors, HIV-infected antiretroviral therapy (ART)-naïve patients and long-term (over 5 years) ART-experienced patients by performing TCR sequencing. We developed a V-J index with 18 parameters which were subdivided into five categories (expression coverage, cumulative percentage of the top tenth percentile, diversity, intra-individual similarity and inter-individual similarity). In ART-naïve patients, 14 of the 18 parameters were significantly altered. Long-term ART recovered ten parameters. The four unrecovered parameters were related to inter-individual similarity. Therefore, these findings indicate that long-term ART could only partially recover TCR V-J pairs and introduce newly impacted V-J pairs. Moreover, these results provide new insights into the V-J pairing of the TCR and into the disturbance of TCR repertoire in HIV infection. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s11427-020-1718-2 and is accessible for authorized users.

Background Tinnitus due to hyperactivity across neuronal ensembles along the auditory pathway is reported. We hypothesized that trigeminal neuralgia patients may subsequently suffer from tinnitus. Using nationwide, population-based data and a retrospective cohort study design, we investigated the risk of tinnitus within 1 year following trigeminal neuralgia. Methods We used the Taiwan National Health Insurance Research Dataset, a claims database, to identify all patients diagnosed with trigeminal neuralgia from January 2001 to December 2014, 12,587 patients. From the remaining patients, we identified 12,587 comparison patients without trigeminal neuralgia by propensity score matching, using sex, age, monthly income, geographic region, residential urbanization level, and tinnitus-relevant comorbidities (hyperlipidemia, diabetes, coronary heart disease, hypertension, cervical spondylosis, temporomandibular joint disorders and injury to head and neck and index year). All study patients (n = 25,174) were tracked for a one-year period to identify those with a subsequent diagnosis of tinnitus over 1-year follow-up. Results Among total 25,174 sample patients, the incidence of tinnitus was 18.21 per 100 person-years (95% CI = 17.66 ~ 18.77), the rate being 23.57 (95% CI = 22.68 ~ 24.49) among patients with trigeminal neuralgia and 13.17 (95% CI = 12.53 ~ 13.84) among comparison patients. Furthermore, the adjusted Cox proportional hazard ratio for tinnitus in the trigeminal neuralgia group was 1.68 (95% CI = 1.58 ~ 1.80) relative to the comparison cohort. Conclusions We found a significantly increased risk of tinnitus within 1 year of trigeminal neuralgia diagnosis compared to those without the diagnosis. Further studies in other countries and ethnicities are needed to explore the relationship between trigeminal neuralgia and subsequent tinnitus.

BACKGROUND This study aimed to evaluate the association between pioglitazone use and the occurrence of head and neck cancer. METHODS Data for this case-control study were retrieved from the Taiwan National Health Insurance Research Database. A total of 21 464 diabetic patients newly diagnosed with head and neck cancers were identified. We used propensity score matching to select 64 392 comparison patients (3:1 ratio). Multiple logistic regression modeling was used to examine the association of head and neck cancer with pioglitazone use in the 5 years preceding the cancer diagnosis. RESULTS Bivariate analysis showed a significant difference in the prevalence of prior using pioglitazone between cases and controls (19.3% vs 18.5%, P

Purpose. To identify potential biomarkers and/or therapeutic targets for bladder cancer we characterized and analysed the composition of the urinary microbiota from bladder cancer and non-cancer patients. Methodology. In this study, we collected urine samples from 29 bladder cancer patients and 26 non-cancer patients. To avoid contamination and the impact of antibiotics, urine specimens were collected in a clean manner prior to antibiotic administration. Using the amplicon-based next-generation sequencing approach, the potential determinant bacteria were estimated in a between-group comparison. The results illustrated the differences in microbiota abundance among cancer and non-cancer patients and the overall number of cases carrying these bacteria. Results. We found that the urine samples contained a conserved microbiota with four phyla ( Firmicutes , Actinobacteria , Proteobacteria and Bacteroidetes ), which accounted for 94.4 % of bacteria in all cases. Comparing the microbiota between the bladder cancer and control group, five genera of bacteria ( Streptococcus , Bifidobacterium , Lactobacillus , Veillonella and Actinomyces ) existed in all samples, but with significant intergroup differences (P

Objectives: Most previous studies on poor immunological responders (PIRs) have been performed on one cohort at one time-point following highly active antiretroviral therapy (HAART). The aim of this study was to investigate whether there are different subtypes of PIR and whether a certain population might achieve better immune reconstitution following longer HAART. Methods: This study was designed as an ambispective cohort study, including a 4–5-year retrospective study and a 2-year prospective follow-up investigation. Thymic output, activated T cell and regulatory T cell (Treg) subset frequencies, expression levels of interferon-stimulated genes, and plasma concentrations of neopterin were determined at 4–5 years and 6–7 years following HAART initiation. Results: PIRs were subdivided into two populations after 4–5 years of HAART, according to the kinetics of T cell recovery. Type II PIRs exhibited a significantly lower percentage of naïve CD4+ T cells and CD31+ naïve CD4+ T cells compared with type I PIRs. After an additional 2 years of HAART treatment, type I PIRs showed a better outcome than type II PIRs. Furthermore, it was found that 2 years of additional HAART could persistently improve thymic output. Conclusions: The two PIR subgroups are different in terms of immune characteristics and the response to prolonged HAART. Keywords: Poor immunological responders, Subdivision, Thymic output, Long-term HAART

BackgroundThe global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR+CD38+ CD8+ T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38+HLA-DR+ CD8+ T population was reported to play contradictory roles in SARS-CoV-2 infection.MethodsA total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3–7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally.ResultsWe revealed that the HLA-DR+CD38+ CD8+ T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR+CD38dim and HLA-DR+CD38hi. We observed a persistent accumulation of HLA-DR+CD38hi CD8+ T cells in severe COVID-19 patients. These HLA-DR+CD38hi CD8+ T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR+CD38dim CD8+ T cells. Moreover, the clinical and laboratory data supported that only HLA-DR+CD38hi CD8+ T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients.ConclusionsOur findings indicated that HLA-DR+CD38hi CD8+ T cells were correlated with disease severity of COVID-19 rather than HLA-DR+CD38dim population.

Spontaneous mutations introduce uncertainty into COVID-19 control procedures and vaccine development. Here, we perform spatio-temporal analysis on intra-host single-nucleotide variations (iSNVs) in 402 clinical samples from 170 patients, which reveals an increase in genetic diversity over time post-symptoms onset within individual patients. Nonsynonymous mutations are over-represented in the pool of iSNVs, but underrepresent at the single nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated within the host (positive selection), and these substitutions tend to be unfixed as SNPs in population (negative selection). Dynamic iSNVs changes in subpopulations of different gender, age, illness severity and viral shedding time displayed a varied fitness selection process among populations. Taken together, our study highlights iSNVs provide a mutational pool shaping the virus rapid global evolution., Graphical Abstract, The Intra-host variations in SARS-CoV-2 provide a mutational pool shaping the virus rapid global evolution. Here, Li et al. illustrate dynamic changes of iSNVs in a longitudinal cohort, and explored a two-step fitness selection process of within-host viral evolution.

Objective To investigate the safety of adenoidectomy and risk factors of re-adenoidectomy, and intend to provide evidence-based information to clinicians for further consideration. Methods and materials This study was based on data obtained from Taiwan’s National Health Insurance Research Database from the period 2002–2011. We utilized that data from the hospitalization group and collected information regarding those individuals who accepted adenoidectomy with or without tonsillectomy and post-adenoidectomy bleeding. Thereafter, we performed univariate and multi-variate analysis to explore the possible risk factors of re-adenoidectomy. Results A total of 5435 individuals who accepted a first adenoidectomy with or without tonsillectomy were collected. After further tracing treatment of these individuals, 107 (1.97%) accepted the revision adenoidectomy until 2011. Post-op bleeding was approximately 0.28%. The revision rate associated with patient age showed the following: 0–4 years (0.61%), 4–12 years (2.06%) and 12–18 years (2.56%). The revision rate associated with surgeon age showed: 28–41 years (1.42%), 41–50 years (2.96%), 50–65 years (2.74%); the surgeons’ surgery volume showed low (4.34%), medium (0.71%), and higher (1.02%). There are 4 diseases (otitis media with effusion, sinusitis, chronic pharyngitis, and sleep disorder) that showed a significant relationship with the revision rate when subject to univariate and multivariate analysis. The revision rate incorporating hospital locations, volumes and levels revealed no significant difference with each other. Conclusions Adenoidectomy is a generally safe surgical procedure, with low complication and low revision rate. Our study indicated that the revision rate of adenoidectomy might be lower when performed by young visiting staff with medium to higher surgical volume in the medium to higher volume hospital. If patients had diseases such as otitis media with effusion, sinusitis, chronic pharyngitis, and sleep disorder, they would be subject to higher rate of re-adenoidectomy. Surgeons should be aware and sufficiently explain this information to the parents before surgery.

This study aimed to investigate the annual incidence of parapharyngeal and retropharyngeal abscess (PRPA) based on 10-year population-based data. Patients with PRPA were identified from the Taiwan Health Insurance Research Database, a database of all medical claims of a randomly selected, population-representative sample of over two million enrollees of the National Health Insurance system that covers over 99% of Taiwan&rsquo, s citizens. During 2007&ndash, 2016, 5779 patients received a diagnosis of PRPA. We calculated the population-wide incidence rates of PRPA by sex and age group (20&ndash, 44, 45&ndash, 64, and &gt, 64) as well as in-hospital mortality. The annual incidence rate of PRPA was 2.64 per 100,000 people. The gender-specific incidence rates per 100,000 people were 3.34 for males and 1.94 for females with a male:female gender ratio of 1.72. A slight increase in incidence rates among both genders over the study period was noted. Age-specific rates were lowest in the 20&ndash, 44 age group with a mean annual incidence of 2.00 per 100,000 people, and the highest rates were noted in the age groups of 45&ndash, 64 and &gt, 64 years with mean annual incidences of 3.21 and 3.20, respectively. We found that PRPA is common in Taiwan, males and older individuals are more susceptible to it, and incidence has increased in recent years.

The spread of SARS-CoV-2 in Beijing before May, 2020 resulted from transmission following both domestic and global importation of cases. Here we present genomic surveillance data on 102 imported cases, which account for 17.2% of the total cases in Beijing. Our data suggest that all of the cases in Beijing can be broadly classified into one of three groups: Wuhan exposure, local transmission and overseas imports. We classify all sequenced genomes into seven clusters based on representative high-frequency single nucleotide polymorphisms (SNPs). Genomic comparisons reveal higher genomic diversity in the imported group compared to both the Wuhan exposure and local transmission groups, indicating continuous genomic evolution during global transmission. The imported group show region-specific SNPs, while the intra-host single nucleotide variations present as random features, and show no significant differences among groups. Epidemiological data suggest that detection of cases at immigration with mandatory quarantine may be an effective way to prevent recurring outbreaks triggered by imported cases. Notably, we also identify a set of novel indels. Our data imply that SARS-CoV-2 genomes may have high mutational tolerance., In this study, Chen and colleagues present genomic sequences of 102 SARS-CoV-2 isolates collected in Beijing. They look closely at genomic variation between isolates that arose as a result of domestic and global transmission. Their data suggest that SARS-CoV-2 genomes have a high mutational tolerance, which may have potential implications for the development of vaccines.

This population-based study aimed to study the association between tinnitus and cervical spondylosis.A case-control study.We retrieved data from the Taiwan Longitudinal Health Insurance Database. We identified 2465 patients with tinnitus (cases) and 7395 comparison patients by propensity score matching. Multivariable logistic regressions were conducted to estimate the odds (OR) of a diagnosis of cervical spondylosis preceding the tinnitus diagnosis relative to controls.We found that 1596 (16.19%) of 9860 sample patients had received a diagnosis of cervical spondylosis before the index date, significantly different between the tinnitus group and control group (17.20% vs. 15.85%,In conclusion, the study shows a positive association between cervical spondylosis and tinnitus. The findings call for greater awareness among physicians about a possible somatosensory component of cervical spine function which may contribute to tinnitus.

Objective : Gut microbiota has been proposed as a pivotal role in the progression of Spondyloarthritis (SpA), however diverse results remain to be synthesized. We performed a systematic review to collect evidence on the characteristic of the gut microbiota in patients with SpA, as compared to controls. Methods : We systematically searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases, through June 1, 2021 for studies that compared gut microbiota of cases with SpA versus healthy controls. Results : Of 3756 records identified, 28 studies from 23 articles were included in the analysis. Results of β-diversity showed SpA patients hold a significantly different microbial composition compared with controls. Several taxa-level differences of gut microbiota between SpA (and its subtypes) cases and controls were identified. Fourteen studies including only patients with ankylosing spondylitis (AS) reported increased amounts of Actinobacteria, Dialister, Streptococcus, and Clostridium bolteae, and decreased amounts of Bacteroidales and Parasutterella in AS cases versus controls in ≥ 3 studies. Dialister invisus was increased in axial-SpA cases versus controls in 3 studies. Bacteroides fragilis was increased in enthesitis-related arthritis (ERA) cases versus controls in 2 studies. For all SpA studies, Proteobacteria, Enterobacteriaceae, and Bacteroidaceae were increased, whereas Bacteroidetes, Bacteroidales, and Akkermansia were decreased in cases versus controls in ≥ 3 studies. Over 40% of the studies showed comparable data of both sex and age between cases and controls. Conclusion : The microbial characteristics of SpA summarized in the systematic review laid the groundwork for evidence-based microbial treatment. The microbial variance among subtypes of SpA remains to be explored. Further studies are needed to elucidate how the altered microbiota participate in the pathogenesis of SpA.

Higher rates of poor cognitive performance are known to prevail among persons with tinnitus in all age groups. However, no study has explored the association between tinnitus and early-onset dementia. We hypothesize that tinnitus may precede or occur concurrently with subclinical or early onset dementia in adults younger than 65 years of age. This case–control study used data from the Taiwan National Health Insurance Research Database, identifying 1308 patients with early-onset dementia (dementia diagnosed before 65 years of age) and 1308 matched controls. We used multivariable logistic regressions to estimate odds ratios (ORs) for prior tinnitus among patients with dementia versus controls. Among total 2616 sample participants, the prevalence of prior tinnitus was 18%, 21.5% among cases and 14.5% among controls (p

Congenital cytomegalovirus (cCMV) infection is the leading environmental cause of childhood hearing impairment. However, its significance remains largely undocumented in many regions of the world. The purpose of this study was to investigate the prevalence and clinical features of cCMV infection in East Asia. Neonates born at a municipal hospital in Taipei were prospectively recruited and underwent concurrent hearing and CMV screenings. Those who failed the hearing screening or screened positive for CMV were subjected to a focused audiological and/or virological surveillance. The characteristics of the newborns and their mothers were compared between the CMV-positive and CMV-negative groups. Of the 1,532 newborns who underwent concurrent hearing and CMV screenings, seven (0.46%) were positive for cCMV infection. All seven CMV-positive newborns were asymptomatic at birth, and none of them developed hearing or other symptoms during a follow-up period of 14.4±6.3 months. The mothers of the CMV-positive newborns demonstrated higher gravidity (2.4 ± 1.4 vs. 2.1 ± 1.2) and parity (2.0 ± 1.2 vs. 1.6 ± 0.7) than those in the CMV-negative group; however, the difference did not reach statistical significance. The prevalence of cCMV infection in Taipei newborns was 0.46%, which is slightly lower than that of other populations and that of a previous report in the Taiwanese population. The relatively low prevalence in this study might be attributed to the improved public health system and decreased fertility rate in Taiwan.

SARS-CoV-2 uses human ACE2 as a primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologs and found that wild-type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells. These results have important implications in the natural hosts, interspecies transmission, animal models, and molecular basis of receptor binding for SARS-CoV-2., The COVID-19 pandemic has caused an unprecedented global public health and economic crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, unlike the SARS-CoV-2-like coronaviruses (CoVs) identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2s from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site-deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activities, respectively. Among the remaining species, ACE2s from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models. IMPORTANCE SARS-CoV-2 uses human ACE2 as a primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologs and found that wild-type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells. These results have important implications in the natural hosts, interspecies transmission, animal models, and molecular basis of receptor binding for SARS-CoV-2.

Objectives Human immunodeficiency virus (HIV) quasispecies diversity presents a large barrier to the eradication of HIV. The aim of this study was to investigate intrahost HIV quasispecies diversity and evolutionary patterns underpinning the mechanisms of viral pathogenesis during antiretroviral therapy (ART). Methods Forty-five participants with HIV-1 infection were enrolled in a follow-up cohort for >84 months in 2004, and received a lamivudine-based first-line ART regimen. Blood samples were collected every 6 months to measure viral load and CD4+ cell count. Ultra-deep sequencing and phylogenetic analysis were used to characterize the dynamics governing quasispecies diversity of HIV-1 circulating between plasma RNA and cellular DNA of participants with treatment failure (TF, n = 20) or virologic suppression (VS, n = 25). Results Analysis of the distribution of intrahost single-nucleotide variations (iSNVs) and their mutated allele frequencies revealed that approximately 65% of the quasispecies co-occurred in plasma HIV RNA and cellular DNA either before or after ART. The number and frequency of iSNVs are more representative of intrahost HIV diversity, and have better generalizability than phylogenetic inference by measurement of phylogenetic associations. Furthermore, drug-resistance-associated mutations (DRAMs) accumulated to high levels, dramatically increasing the DRAM-to-total-mutation ratio for TF patients. Linear regression analysis revealed that emergent mutations accumulated faster in TF patients compared with VS patients, at a rate of 0.02 mutations/day/kb. Conclusions Based on iSNV analysis, the results demonstrate the dynamics of intrahost HIV quasispecies diversity in patients on ART, and provide a novel insight into the persistence of HIV and development of DRAMs.

Background: The aim of this study was to compare the risk of developing sudden sensorineural hearing loss (SSHL) in patients with hypopharyngeal cancer with that in patients with nasopharyngeal carcinoma (NPC). Methods: A population-based, retrospective cohort study was performed using the Taiwan National Health Research Database databank. Patients selected for this study were diagnosed with hypopharyngeal cancer or NPC and treated with radiotherapy in the period from 2001 to 2004. Routine follow-up was conducted for 8 years (2004–2012), and the incidence of SSHL was calculated at the final follow-up. Results: There was no significant difference in the risk of developing SSHL between the hypopharyngeal cancer group and its control group (p = 1.000). In hypopharyngeal cancer and NPC groups, the rates of SSHL were 0.12% and 1.00%, respectively (p < 0.001). The cumulative hazard of SSHL during the follow-up period was significantly higher in the NPC group than in the control group (p < 0.001). Conclusion: Radiotherapy in patients with hypopharyngeal cancer did not increase the risk of developing SSHL, but postirradiation NPC was significantly associated with an increased incidence of SSHL.

This study aimed to evaluate the prevalence of peripheral vestibular disorders in an Asian population of predominantly Han Chinese ethnicity.Cross-sectional study.Patients with a peripheral vertigo disorder were identified from the Taiwan Health Insurance Research Database, a database of all medical claims of a randomly selected, population-representative sample of 2 million enrollees of Taiwan's National Health Insurance system covering over 99% of Taiwan's citizens. In 2016, 59,986 patients received a diagnosis of peripheral vestibular disorders in Taiwan. We calculated the population-wide prevalence rates of peripheral vestibular disorders in 2016 by sex and age group (20 to 24, 25 to 29, 30 to 34, 35 to 39, 40 to 44, 45 to 49, 50 to 54, 55 to 59, 60 to 64, 65 to 69, and ≥ 70 years) stratified into five urbanization levels.The prevalence rate of peripheral vestibular disorders was 2,833.4 per 100,000 population during the year. Prevalence of Meniere's disease was 70.4 per 100,000, benign paroxysmal positional vertigo, 446.4, vestibular neuritis 307.2, and other or unspecified peripheral vestibular dizziness, 2,009.5 per 100,000. Prevalence rates steadily increased with age for every type of peripheral vestibular disorder, and were higher among females compared to males. The female-to-male gender ratios were 1.84, 1.89, and 1.93 for Meniere's disease, vestibular neuritis, and other peripheral vestibular dizziness, respectively. Counties with the lowest urbanization level had the highest prevalence rates of all types of peripheral vestibular disorders except vestibular neuritis.Results showed that peripheral vestibular disorders are common in Taiwan, increase with age, are predominantly female, and show higher prevalence in rural areas.2b Laryngoscope, 131:639-643, 2021.

Objective: Despite studies reporting a possible association between malignant otitis externa (MOE) and diabetes, there are no large-scale population-based empirical studies. This nationwide, population-based case-control study explored the association of MOE occurrence with previously diagnosed diabetes. Methods: Data were retrieved from Taiwan’s National Health Insurance Research Database, 753 patients with MOE (cases) and 2 259 propensity score-matched patients without MOE (controls). Multiple logistic regressions were conducted to examine the association of MOE with previously diagnosed diabetes. Results: In total, 728 (24.2%) out of 3 012 sample patients had diabetes prior to the index date. Chi-square test revealed a significant difference in diabetes prevalence among cases and controls (54.8% vs 13.9%, p Conclusions: This study found an association between MOE and diabetes. One clinical practice implication of our study is that when a patient with diabetes complains of otalgia or otorrhea, and physical examination shows swelling of the ear canal or granulation growth, physicians should consider the possibility of MOE.

Neutropenia and impaired functions were common manifestation in antiretroviral therapy (ART) in both naïve and experienced PLWHA. Granulopoiesis can be divided into two phases: lineage determination and committed granulopoiesis. However, stage-specific impairment of granulopoiesis in PLWHA with neutropenia remains unclear. A total of 48 ART-naïve and 49 ART-experienced PLWHA from 2016 to 2018 were recruited and divided into non-, mild-, and moderate-to-severe-neutropenia groups according to their neutrophil counts. The bone marrow aspirates and peripheral blood were collected and analyzed by multicolor flow cytometry for granulocyte subsets, hematopoietic stem/progenitor cells (HSPC), apoptosis, and emigration and retention of different subsets. Compared with healthy donors, the percentages of circulating segmented neutrophils were significantly decreased along with an increase of immature neutrophils in both groups. ART-naïve patients with moderate to severe neutropenia exhibited decreased proportion and accelerated apoptosis of relative mature segmented neutrophils. In contrast, ART-experienced patients with neutropenia displayed decreased proportion of granulocyte macrophage progenitors, indicating a defect at a stage of lineage determination. Meanwhile, ART-experienced patients with neutropenia also the expression of CXCR4 segmented neutrophils, suggesting an increased retention of segmented neutrophils inn the bone marrow. ART-naïve patients with neutropenia is caused by increased apoptosis of relatively differentiated neutrophils at committed granulopoiesis, whereas impaired lineage determination and enhanced retention of segmented neutrophils contribute to in ART-experienced patients.

Ethnopharmacological relevance The genus Viscum comprises approximately 100 species that are mainly distributed across Africa, Asia and Europe. The extracts and preparations of Viscum species are widely used as common complementary and alternative medicines in the treatment of rheumatism and cancer. Aim of the review This review aims to explore the medicinal properties of twelve species belonging to the genus Viscum for potential therapeutic applications. Materials and methods We collected online information (including PubMed, CNKI, Google Scholar, and Web of Science) from January 1915 to April 2021 and knowledge from classical books on Chinese herbal medicines available for 12 species of the genus Viscum, including Viscum coloratum (Kom.) Nakai, Viscum album L., Viscum articulatum Burm. f., Viscum liquidambaricola Hayata, Viscum ovalifolium DC., Viscum capitellatum Sm., Viscum cruciatum Sieber ex Boiss., Viscum nudum Danser, Viscum angulatum B.Heyne ex DC., Viscum tuberculatum A.Rich., Viscum multinerve Hayata, and Viscum diospyrosicola Hayata. Results At least 250 different compounds have been reported across twelve Viscum species, including amino acid and peptides, alkaloids, phenolic acids, flavonoids, terpenoids, carbohydrates, fatty acids, lipids, and other types of compounds. In particular, for Viscum coloratum (Kom.) Nakai and Viscum album L., the plants, preparations, and bioactive components have been thoroughly reviewed. This has allowed to elucidate the role of active components, including lectins, viscotoxins, flavonoids, terpenoids, phenolic acids, and polysaccharides, in multiple bioactivities, such as anti-cancer, anti-rheumatism arthralgia, anti-inflammation, anti-cardiovascular diseases, enhancing immunity, and anti-chemotherapy side effects. We also evaluated quality control methods based on active compounds, in vivo exposure compounds, and discriminated chemical markers. Conclusions This is the first report to systematically review the pharmaceutical development history, chemical composition, clinical evidence, pharmacological activity, discriminated chemical markers, in vivo exposure, and quality control on twelve distinct species of Viscum plants with medicinal properties. The significant safety and efficacy, along with the minor side effects are constantly confirmed in clinics. The genus Viscum is thus an important medicinal resource that is worth exploring and developing in future pharmacological and chemical studies.

Objectives: Given the improvements in antiretroviral therapy (ART) in recent years, more pediatric HIV patients receiving ART are reaching adolescence and adulthood. This study investigated the influence of poor virological response (low-level viremia (LLV) and virological failure (VF)) on the immune system of these patients. Methods: HIV-infected, ART-experienced pediatric patients (n = 206) were enrolled in this cross-sectional study. The patients were subdivided into school-age children/early adolescents, middle adolescents, and late adolescents/young adults according to their age, and further classified into virological suppression (VS), LLV, and VF groups according to plasma viral load (pVL) measurement. Thymic output, T cells subsets, and immune activation were analyzed by flow cytometry. Results: Compared with VS patients, VF patients displayed decreased CD4+ T cell counts, while LLV and VS patients had comparable CD4+ T cell counts regardless of age. Compared with VS patients, LLV and VF patients had higher percentages of CD8+HLA-DR+ and CD8+CD38high T cells, and the immune activation was positively correlated with pVL in VF and LLV patients. Thymic output levels (CD31+) and regulatory T cell subpopulations in LLV and VF patients were comparable to those in VS patients. LLV patients showed comparable percentages of T cell subsets (TN, TCM, TEMRA, and TEM) as VS patients in all age groups. Conclusions: LLV causes excessive immune activation although it does not impair T cell recovery or naïve-to-memory T cell conversion in pediatric patients living with HIV. Therefore, T cell immune activation should be monitored at the management of LLV during ART. Keywords: Pediatric HIV/AIDS, Antiretroviral therapy, Low-level viremia (LLV), Immune activation, Thymic output

Ischemic tolerance is an endogenous protective mechanism that refers to the ability of a sublethal stimulus to induce tolerance to a subsequent lethal ischemic injury. It was first demonstrated in neuronal cells of the gerbil hippocampus (1), after which it has aroused a considerable interest as a possible therapeutic modality for ischemic brain diseases. However, to expose patients to brief periods of ischemia is both impractical and unsafe. Chemical preconditioning substances that can induce ischemic tolerance, such as endotoxins, cytokines, metabolic inhibitors, potassium, chloride, and neurotoxin 3-nitro-propionic acid (1-5) have also been investigated but were found to have limited clinical application due to toxicity and side effects. A variety of experimental models of cerebral ischemia have found that hyperbaric oxygen preconditioning (HBOP) induces ischemic tolerance and attenuates cerebral injury (6-17). Its protective effect is also visible in other conditions leading to oxidative stress, with final anti-apoptotic result, as well as modulation of neutrophin and immune systems (6-17). The blood-brain barrier (BBB), a highly selective permeability barrier, consists of tight junctions (TJ) between capillary endothelial cells, the basal lamina, pericytes, and astrocyte end-feet (18). It plays an important role in maintaining cerebral homeostasis by restricting molecular movement from the cerebral capillaries to the brain tissue. BBB breakdown can result in a vasogenic edema, hemorrhage, and neuronal cell death, all of which can contribute to the pathophysiology of cerebral ischemic diseases (19). TJs between cerebral endothelial cells are formed by complex interactions of cytoskeletal proteins and tight junction proteins (TJPs), including claudins, occludin, zonula occludens (ZO), and cingulin (20). TJPs increase endothelial electrical resistance and decrease paracellular permeability (21). Changes in their expression can lead to the loss of BBB integrity and BBB breakdown (22). HBOP has been associated with reduced brain edema, decreased infarct volume, and improved neurological function (6-17), but it is not clear whether it directly affects the BBB, particularly TJPs expression. This should be clarified in order to find new therapeutic strategies to attenuate BBB permeability in cerebral ischemic disorders. Therefore, the aim of this study was to examine the HBOP effect on hypoxia-induced BBB breakdown in vitro and the changes of occludin and ZO-1 expression.

Patients with risk factors including younger age, mastoiditis, external ear disease, treatment by older surgeons, and concomitant mastoidectomy should receive detailed management to minimize the probability of re-operation for chronic otitis media (COM).Although COM remains a common ear disease requiring surgical intervention, its re-operation risks are less well-documented. This study aimed to compare patients with COM who underwent re-operation and those patients with no re-operation, and identify the risks of re-operation.This retrospective cohort study analyzed the trend of COM surgery from 1999-2009, and identified the re-operation risks of 18 895 patients with COM who underwent surgery from 2002-2006 using the National Health Insurance Research Database in Taiwan.Among the study population, 129 patients underwent revision surgery during a 5.5 ± 1.5 year follow-up period. A univariate logistic regression analysis showed that the re-operation rate was significantly higher in patients under 18 years of age, those with mastoiditis, disorders of external ear, treatment by surgeons of 50-64 years of age, use of a very high volume surgeon, and combined surgery with mastoidectomy. A multivariate analysis further limited the re-operation risk factors to younger patients, those with mastoiditis, external ear disorders, treatment by older surgeons, and concomitant mastoidectomy.

Rationale: We studied the feasibility of total arathyroidectomy(tPTX)+multi-point transplantation in the forearm for treatment of secondary hyperparathyroidism. Considering the controversial nature of the appropriate timing for and location of this type of surgery, relevant research is relatively rare. Our experience may be a relatively successful one. Patient concerns: Our patient was a 28-year-old woman with end-stage renal disease (ESRD), who was on dialysis for 7 years, and a 2-year history of progressively aggravated bone pain. She also had hypercalcemia and hyperphosphatemia. Diagnoses: Given the patient's history of long-term dialysis, bone pain, high levels of intact parathyroid hormone(i-PTH) and hypercalcemia, we performed ultrasonography which showed solid nodules in the bilateral parathyroid glands. She was accordingly diagnosed with SHPT. Interventions: The patient underwent tPTX+multi-point subcutaneous transplantation in the forearm. Outcomes: Her i-PTH level dropped to < 300 pg/mL, and the symptoms of bone pain markedly reduced after surgery. Lessons: Total parathyroidectomy+multi-point subcutaneous transplantation in the forearm may be a reliable surgical approach for patients with ESRD.

This study aimed to evaluate the relationship between sudden sensorineural hearing loss (SSNHL) and MVP using a population-based dataset. Data for this case-control study were retrieved from the Taiwan Longitudinal Health Insurance Database. In total, 3399 cases of newly diagnosed SSNHL were identified. We used propensity score matching to select 3399 comparison patients (one for every case) from the same dataset. The selected matching variables included age, sex, monthly income, geographical location, urbanization level of the patient's residence, hypertension, diabetes, and hyperlipidemia. Chi-squared tests were used to compare differences in sociodemographic characteristics, while conditional logistic regression analyses were used to examine the association of SSNHL with previously diagnosed MVP. Of the 6798 sampled subjects, 131 (1.93%) patients had received a diagnosis of MVP prior to the index date. A significant difference in the prevalence of prior MVP between cases and controls (2.41% vs. 1.44%, p = 0.004) was observed. The conditional logistic regression analysis conditioned on gender, age, monthly income, urbanization level, geographic region, hyperlipidemia, diabetes, and hypertension suggested that the odds ratio of prior MVP for cases was 1.69 (95% confidence interval (CI): 1.18~2.42) compared to controls. Our study found that patients with MVP had a 1.69-fold higher risk of getting SSNHL compared to patients without MVP.

The relationship between obstructive sleep apnea (OSA) and chronic rhinosinusitis (CRS) still remains unclear. This retrospective cohort study aimed to investigate the relationship between OSA and subsequent CRS using a population-based dataset. The study used data from the Taiwan Longitudinal Health Insurance Database 2005. We selected 971 patients with OSA for the study cohort and 4855 patients without OSA for the comparison cohort. Each patient was tracked for 5 years to determine those who were subsequently diagnosed with CRS. Stratified Cox proportional hazard regression analyses were performed to examine the association of OSA with subsequent CRS. The results revealed that 161 (2.76%) of the total sampled patients were subsequently diagnosed with CRS. Subsequent incidences of CRS were found in 64 (6.59%) patients with OSA and 97 (2.00%) patients without OSA. The adjusted hazard ratio (HR) of subsequent CRS for patients with OSA was 3.18 (95% confidence interval: 2.27~4.45) compared to those without OSA. Furthermore, the HR for CRS was similar for subjects with OSA for both genders (with an adjusted HR of 3.44 for males and 2.63 for females). We concluded that patients with OSA had a higher risk of subsequent CRS compared to patients without OSA regardless of sex.

OBJECTIVE Although plenty of researchers have reported systemic effects originating from chronic periodontitis (CP) on potentially distal inflammatory processes, such as those leading to coronary heart disease, cerebrovascular disease, and cancer, no study has reported the association between CP and sudden sensorineural hearing loss (SSNHL). The present study explored the association between CP and SSNHL using a large, population-based dataset in Taiwan. STUDY DESIGN A case-control study. SETTING Taiwan. PATIENTS We used administrative claims data from the Taiwan National Health Insurance program to identify 2,436 subjects with SSNHL and to randomly select 7,308 controls. MAIN OUTCOME MEASURES A conditional logistic regression analysis was conducted to calculate the odds ratio (OR) for having been previously diagnosed with CP between cases and controls. RESULTS In total, 1,663 (17.1%) of the 9,744 sampled subjects had received a CP diagnosis before the index date; 520 (21.4%) were cases and 1143 (15.6%) were controls. The χ2 test suggested that there was a significant difference in the prevalence of previous SSNHL between cases and controls (p < 0.001). The conditional logistic regression revealed after adjusting for hypertension, diabetes, hyperlipidemia, renal disease, coronary heart disease, obesity, and stroke, the OR of having previously received a CP diagnosis among cases was 1.44 (95% CI = 1.29∼1.63) that of controls. CONCLUSION This study found that SSNHL was significantly associated with a previous diagnosis of CP. Further prospective studies are warranted to confirm our findings and clarify the underlying pathomechanism.

Objectives/Hypothesis Although chronic periodontitis (CP) and chronic rhinosinusitis (CRS) both share immunological disturbances as pathological factors, no prior study has investigated the risk for CP among patients with CRS. This study set out to provide an estimation of risk by utilizing a cohort study design to leverage the statistical power of a population-based dataset in Taiwan. Study Design A retrospective cohort study. Methods In total, 13,782 CRS subjects were included in the study cohort and 41,346 subjects were randomly extracted for the comparison cohort. We individually tracked each subject in this study (N = 55,128) for a 5-year period following their index date to identify those subjects who received a subsequent diagnosis of CP. Cox proportional hazards regression analysis was conducted to calculate the 5-year risk of subsequent CP following a diagnosis of CRS among the sampled subjects. Results The incidence rate of CP during the 5-year follow-up period was 5.12 (95% confidence interval [CI], 4.95-5.30) per 100 person-years and 3.24 (95% CI, 3.17-3.30) per 100 person-years for the study and comparison cohort, respectively. Cox proportional hazards regression revealed that the hazard ratio for CP during the 5-year follow-up period for subjects with CRS was 1.59 times (95% CI, 1.52-1.67) that of comparison subjects after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, and hyperlipidemia, and censoring for cases who died during the 5-year follow-up period. Conclusions This study detected an increased risk for CP among patients suffering from CRS. CRS patients should be alerted to pay particular attention to their oral hygiene practices to prevent both CP and its downstream sequelae.

The microbiological transformation of the triterpene nigranoic acid (3,4-secocycloarta-4(28),24(Z)-diene-3,26-dioic acid) (1) to 3,4-secocycloarta-4(28),17(20),24(Z)-triene-7β-hydroxy-16β,26-lactone-3-oic acid (2) and 3,4-secocycloarta-4(28),17(20)(Z),24(Z)-triene-7β-hydroxy-16β-methoxy-3,26-dioic acid (3) by the freshwater fungus Dictyosporium heptasporum YMF1.01213 has been demonstrated. The structures of the biotransformation products were determined by spectroscopic and MS analyses. Compound 2, characterized by the presence of a formed C-16/C-26 ester bridge, provided a novel nine-membered lactone ring structural skeleton for 3,4-secocycloartane triterpenoid derivatives. In addition, Compounds 1-3 exhibited weak anti-HIV activity in vitro. Compounds 2 and 3 were reported for the first time as natural product derivatives.

Aim This study set out to explore the association between obstructive sleep apnoea (OSA) and prior chronic periodontitis (CP) by utilizing a population-based data set with a case-control design in Taiwan. Materials and Methods We included 7673 subjects with OSA as cases, and randomly selected 21,963 subjects without a history of OSA as controls. We performed conditional logistic regression analyses to explore the association between OSA and having been previously diagnosed with CP. Results There was a significant difference in the prevalence of prior CP between cases and controls (33.8% versus 22.6%, p

Objectives The study aimed to estimate the risk of developing chronic rhinosinusitis (CRS) among children who had undergone a tonsillectomy by utilizing a cohort study based on a population-based database. Methods Data for this retrospective cohort study were sourced from the Taiwan ”Longitudinal Health Insurance Database 2000”. We included 202 children who had undergone a tonsillectomy as the study group and 2020 sex- and age-matched children as the comparison group. We used stratified Cox proportional hazard regressions to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI) for CRS during the 3-year follow-up period. Results Of 2222 sampled children, the incidence rate of CRS during the 3-year follow-up period was 3.2 (95% CI = 2.0–4.8) 1000 person-years; 18.2 (95% CI = 9.1–32.5) per 1000 person-years and 1.7 (95% CI = 0.8–3.0) per 1000 person-years for the study and comparison group, respectively. The stratified Cox proportional analysis showed that the adjusted hazard ratio for CRS during the 3-year follow-up period was 8.28 (95% CI = 3.24–21.16) for children who had undergone a tonsillectomy than comparison patients. Conclusions We demonstrated that the risk of developing CRS is significantly increased among children who have undergone a tonsillectomy.

Palatoplasty can significantly decrease their middle ear re-intubation rate with a relatively lower hazard ratio compared to children who underwent VTI only.In children with cleft palate, questions remain about the overall effect of ventilation tube insertion (VTI) and palatoplasty for their OME. A large-scale study might offer more evidence for the roles of palatal surgery.This was a retrospective birth cohort study based upon a national database. We analyzed children born between 1999-2004 and diagnosed as cleft palate and/or lips. These children, according to their surgeries, were separated into two groups: (1) VTI only, and (2) VTI and palatoplasty. Kaplan-Meier analysis and log-rank test were used to calculate their cumulative tube re-insertion rates. Their hazard ratios of tube re-insertion were also analyzed.In total, 1205 cleft children were collected, with 151 in the VTI only group and 1054 in the VTI + palatoplasty group. Ventilation tube re-insertion rates were significantly lower in the VTI + palatoplasty group (p = 0.002). The cumulative re-insertion rates also showed a significant difference (p = 0.001). When compared to the VTI only group, the adjusted hazard ratio was 0.528 in the VTI + palatoplasty group (p = 0.001).

Objectives: The primary aim of this study was to obtain the mean hearing thresholds among school-age children residing in the Datong and Jhongshan Districts of Taipei City, Taiwan. Design: Hearing thresholds were obtained from a stratified sample of 1411 students in grades 1, 4, 7, and 10 based on their participation in the annual health examination of school-age children carried out by the Taipei City Government. After otoscopic examination, audiometric testing was undertaken at 0.5 to 4 kHz along with tympanometric screening. The means and SDs obtained from these examinations are reported by grade, gender, ear, and frequency. Results: The mean hearing thresholds ranged between 6.8 and 16.7 dB HL, with the highest (poorest) hearing threshold being obtained at a test frequency of 0.5 kHz. At all the tested frequencies, the hearing thresholds of boys were found to be higher than those of girls. Logistic regressions demonstrating that those students with the highest odds ratios of hearing loss were to be found in the sample of children in grade 1. The odds ratios of hearing loss were also found to be higher among boys than girls and for the left ear rather than the right. Conclusions: These results indicate that the mean thresholds among the study sample were well above (meaning poorer) the pure-tone average of 15 dB HL, as recommended in a previous study. Therefore, the results of this study suggest the need to further determine the etiology of hearing loss among children in grades 1, 4, 7, and 10 in the Datong and Jhongshan Districts of Taipei City and perhaps Taiwan.

Four new cycloartane triterpenoids, angustific acid A (1), angustific acid B (2), angustifodilactone A (3) and angustifodilactone B (4) were isolated from the branches of Kadsura angustifolia together with six known compounds, micranoic acid B (5), nigranoic acid (6), schisandrin (7), schisantherin D (8), interiotherin B (9), schisantherin B (10). Their structures were established on the basis of extensive spectroscopic data analyses and comparison with spectroscopic data reported. Compound 1, characterized by the presence of a C-16/C-17, C-20/C-21 conjugated diene and a C-1/C-7 ester bridge formed in rings A and B, provided a novel structural skeleton for 3,4-secocycloartane triterpenoid derivatives. In addition, the anti-HIV activities of these compounds were determined in infected C8166 cells, and it was found that angustific acid A (1) exhibited the most potent anti-HIV activity with an EC(50) value of 6.1 μg/mL and a therapeutic index of more than 32.8.

Background and Purpose— The occurrence of preeclampsia-eclampsia during pregnancy has been reported to increase the risk of stroke in mainly Western populations. However, few studies have evaluated stroke risk in Asian populations and followed women beyond the early postpartum period. Thus, the present study determined the risk of stroke in women in Taiwan during pregnancy and the first postpartum year. Methods— A population-based cohort study was performed on 1 132 019 parturients during 1999 to 2003 using a dataset linking birth certificates and National Health Insurance hospital discharge data. Stroke-free survival rates were estimated using the Kaplan–Meier method, and the log-rank test was used to examine the effect of preelampsia-eclampsia on the prevalence of stroke. Sociodemographic factors and obstetric complications were used in multivariate logistic regression models to determine the adjusted odds ratios of preeclampsia-eclampsia on the risk of hemorrhagic and ischemic stroke during pregnancy and within the first postpartum year. Results— The incidence of stroke was 21.47 cases per 100 000 deliveries. There were 139 cases of hemorrhagic stroke and 107 cases of ischemic stroke. The respective adjusted relative risk of preeclampsia-eclampsia for hemorrhagic and ischemic stroke were 10.68 (95% CI, 3.40 to 33.59) and 40.86 (95% CI, 12.14 to 137.47) within 3 months antepartum; 6.45 (95% CI, 1.42 to 29.29) and 34.71 (95% CI, 11.08 to 108.68) in the first 3 days postpartum; 5.61 (95% CI, 0.71 to 44.10) and 11.23 (95% CI, 2.45 to 51.59) from 3 days to 6 weeks postpartum; 11.76 (95% CI, 4.05 to 34.11) and 11.60 (95% CI, 3.30 to 40.82) from 6 weeks to 6 months pospartum; and 19.90 (95% CI, 7.75 to 51.11) and 4.35 (95% CI, 0.58 to 32.92) from 6 months to 12 months postpartum. Conclusions— Women with preeclampsia-eclampsia have a significantly higher risk of stroke during pregnancy and in the first postpartum year. These results suggest that women with preeclampsia-eclampsia should be closely monitored even after pregnancy.

Whereas the impression that poor oral hygiene is linked to the development of sialolithiasis may be widely accepted, very few studies provide evidence to support this. This study therefore aimed to evaluate the association between chronic periodontitis (CP) and the subsequent development of salivary gland stone based on a nationwide coverage database.A case-control study.A total of 987 subjects with sialolithiasis were included as cases. In a ratio of five controls per case, 4,935 controls matched in terms of sex and age group were selected. Conditional logistic regression analysis was performed to determine the possible association of sialolithiasis with previously diagnosed CP.The prevalence of prior CP between cases and controls demonstrated that 1,831 (30.9%) out of the 5,922 sampled subjects had prior CP. By Chi-square test, there was a significant difference in the prevalence of prior CP between the cases and controls (36.8% vs. 29.7%, P 0.001). By conditional logistic regression analysis, the odds ratio (OR) of prior CP for cases was 1.37 (95% confidence interval [CI], 1.19-1.56) compared to the controls after adjusting for geographic location and tobacco use. Further analyzing the relationship between sialolithiasis and prior CP according to sex, sialolithiasis was associated with prior CP regardless of sex. The adjusted OR of prior CP for the cases was 1.34 (95% CI, 1.10-1.64) and 1.41 (95% CI, 1.15-1.73) for males and females, respectively, when compared to controls.This study demonstrates an association between CP and sialolithiasis.3b.

Primary non-Hodgkin’s lymphoma (NHL) of the sinonasal tract is uncommon. Morphologically and radiographically, sinonasal lymphomas are difficult to distinguish fromother malignant neoplasms or non-neoplastic processes. However, there is no general consensus about the need of routine histopathological examination for nasal polyps among otolaryngologists. We present a case of primary sinonasal NHL mimicking chronic hinosinusitis and debate the issue of routine histopathological examination. We suggest that all tissues removed from the sinonasal tract during surgery must be submitted for histopathological examination. Failure to do so may miss diagnosis and delay appropriate treatment.

Neovascularization, including angiogenesis, arteriogenesis and vasculogenesis, occurs in physiological and pathological state. Efficient and controlled reconstruction of functional vascular network is necessary. Nerves and blood vessels establish intricate branching network in every organ which share anatomical and functional characteristics. Nerves direct vessel branching patterns and arterial differentiation in the developmental embryonic limb skin. Various neurotransmitters exert antiapoptotic, chemotactic and proliferative effect on EC and SMC, and modulate all the phases of neovascularization. Hence, we proposed that the perivascular nerves may play critical roles in neovascularization.

Chloranthus, a genus of the family Chloranthaceae, which is mainly distributed in eastern and southern Asia, has been used in Chinese folk medicine due to its antitumor, antifungal, and anti-inflammatory activities. This review compiles the research on isolation, structure elucidation, structural diversity, and bioactivities of Chloranthus secondary metabolites reported between 2007 and 2013. The metabolites listed encompass 82 sesquiterpenoids, 50 dimeric sesquiterpenoids, 15 diterpenoids, one coumarin, and five other compounds. Among them, dimeric sesquiterpenoids, the characteristic components of plants from the genus Chloranthus, have attracted considerable attention due to their complex structures and significant biological features, e.g., antitumor, antibacterial, antifungal, anti-inflammatory, and hepatoprotective activities, and potent and selective inhibition of the delayed rectifier (IK) K(+) current and tyrosinase.

Objectives/Hypothesis Although it is known that inflammatory processes can elevate the risk of cancer, to date the association between allergic rhinitis (AR) and nasopharyngeal carcinoma (NPC) remains unknown. This study aimed to evaluate the association between NPC and AR based on a population-based database in Taiwan. Study Design A case-control study. Methods In total, 1,799 NPC cases and 5,397 randomly selected controls without NPC were included. We evaluated the prevalence and risk of prior AR between cases and controls. We also performed a conditional logistic regression analysis to calculate the odds ratio (OR) for having been previously diagnosed with AR between cases and controls. Results In total, 2,453 of the 7,196 study subjects (34.1%) had previously received an AR diagnosis; 875 (48.6%) were cases and 1,578 (29.2%) were controls (P