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Qun Li,1,2 Fengting Yu,1,2 Chuan Song,1– 3 Hongxin Zhao,1,2 Qing Xiao,1,2 Xiaojie Lao,1,2 Siyuan Yang,1,2 Yunxia Tang,1,2 Fujie Zhang1,2 1Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Clinical Center for HIV/AIDS, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, People’s Republic of ChinaCorrespondence: Fujie Zhang, Clinical and Research Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Tel +86 10 84322581, Email treatment@chinaaids.cnObjective: In this study, we aimed to determine drug-resistance mutations (DRMs) in HIV-1 patients with low-level viremia (LLV) and explored the performance of next-generation sequencing (NGS) in detecting HIV DRMs by using LLV samples.Methods: Overall, 80 samples with LLV were amplified and sequenced using a commercial Sanger sequencing (SS) genotyping kit. Furthermore, 51 samples successfully sequenced using SS were simultaneously subjected to NGS. Genotyping success rates of various viremia categories by two sequencing methods were calculated. Stanford HIV-1 drug-resistance database (HIVdb version 8.9) was used to analyze the DRMs. In the NGS assay, a threshold of 5% was considered for reporting low-frequency variants, and the DRMs detected using SS and NGS were compared.Results: The overall success rate of PR/RT regions was 88.1% (67/80) using SS and 86.3% (44/51) using NGS. Furthermore, a significant linear trend was noted between viral load and the genotyping success rate. A total of 38.8% (26/67) participants harbored at least one mutation, as revealed through SS. Moreover, the prevalence of DRMs in persistent LLV was significantly higher than that in intermittent LLV (62.1% vs. 21.1%; P < 0.05). A total of 69 DRMs were detected using the two sequencing methods at the threshold of 5%. Moreover, 10 DRMs missed by SS were detected using NGS, whereas 8 DRMs missed by NGS were detected by SS.Conclusion: Our data suggested that the genotyping resistance testing is necessary to guide antiretroviral therapy optimization in LLV patients.Keywords: HIV-1, low-level viremia, drug-resistance mutation, next-generation sequencing

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.

Ankylosing spondylitis (AS) is the prototype of a group of systemic inflammatory diseases referred to as spondyloarthritis. Comorbid inflammatory bowel disease and changed gut microbiota in AS have attracted attention to the influence of gut–joint axis and encouraged treating AS by targeting gut microbiota. Here we first reported a patient with refractory AS and comorbid ulcerative colitis (UC) who underwent three fecal microbiota transplantations (FMTs). Inadequate response to conventional treatments including tumor necrosis factor inhibitors impelled FMT as alternative therapy. Notable improvements in AS and UC accompanied with changed fecal microbiota were recorded at 1 week post-FMT1. Further recovery was found after the other two FMTs, and a roughly stable status was maintained in the follow-up period. More studies are needed to validate the effectiveness of FMT in AS and its mechanisms.

Stable CO32− in layered double hydroxides (LDHs) was deintercalated using a carbonated NaCl solution. HCO3− exhibits lower affinity to LDHs and can be easily replaced by Cl−.

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.

In previous studies, researchers have used singing to treat respiratory function in patients with spinal cord injury. However, few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury. Vocal respiratory training (VRT) is a type of vocal muscle-related treatment that is often a component of music therapy (MT) and focuses on strengthening respiratory muscles and improving lung function. In this randomized controlled study, we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury. Of an initial group of 37 patients, 26 completed the music therapy intervention, which comprised five 30-minute sessions per week for 12 weeks. The intervention group (n = 13) received VRT training delivered by professional certified music therapists. The control group (n = 13) received respiratory physical therapy delivered by professional physical therapists. Compared with the control group, we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention. Further, the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification, with an increased number, path length, thickness, and density of nerve fiber bundles. These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2020-013-1) on April 1, 2020, and was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR2000037871) on September 2, 2020.

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.

Purpose: To investigate the clinical efficacy of avatrombopag, an oral thrombopoietin receptor agonist, versus subcutaneous recombinant human thrombopoietin (rh-TPO) in the treatment of severe thrombocytopenia (TCP) associated with chronic liver disease (CLD).Methods: Clinical data of 250 patients with severe TCP associated with CLD were collected in a single hospital from January 2019 to January 2022. The main parameters measured were the therapeutic response rate, changes in platelets (PLTs), and adverse events. Propensity score matching (PSM) was used to avoid possible selection bias.Results: After PSM, a total of 154 patients were enrolled in the study: 77 in the avatrombopag group and 77 in the rh-TPO group. There was no statistically significant difference between the two groups in the effect of increasing the PLT count (Waldχ2 = 1.659, p = 0.198; Waldχ2 = 0.220, p = 0.639). In addition, no interaction between time and different medications was found (Waldχ2 = 0.540, p = 0.910; Waldχ2 = 1.273, p = 0.736). Interestingly, in the subgroup analysis, both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A (88.89% vs. 63.41%, p =0.003; 81.33% vs. 61.76%, p = 0.043). Fewer patients reported dizziness in the avatrombopag group than in the rh-TPO group both before and after PSM (7.8% vs. 25.0%; 7.8% vs. 24.7%, p < 0.05).Conclusion: Both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A and showed a lower incidence of dizziness in all patients.

Objectives To determine the frequency of symptoms meeting Rome IV functional bowel disorder (FBD) in patients with ankylosing spondylitis (AS), investigate factors associated with FBD symptoms, and assess whether having FBD symptoms might influence AS disease activity. Methods In this cross-sectional study, we enrolled 153 AS patients without known colonic ulcers and 56 sex- and age-matched controls to evaluate FBD (or its subtypes) symptoms. Disease characteristics were also evaluated in the AS group. Results Sixty (39.2%) of 153 AS patients had FBD symptoms, which were more prevalent than controls (23.2%). Besides, symptoms compatible with irritable bowel syndrome (IBS) and chronic diarrhoea were detected in 18 and 43 AS patients, respectively. For the AS group, multivariable logistic regression analyses showed that symptoms of FBD, IBS, and chronic diarrhoea were negatively associated with using non-steroidal anti-inflammatory drugs and positively associated with comorbid fibromyalgia, respectively. In exploration about the effects of FBD (or its subtypes) symptoms on AS disease activity by multivariable linear regression analyses, FBD symptoms and chronic diarrhoea had universal positive associations with assessments of AS disease characteristics, respectively. Conclusions Patients with AS had frequent symptoms compatible with FBD, IBS, and chronic diarrhoea, proportions of which were lower in those with non-steroidal anti-inflammatory drug use. The improvement of FBD symptoms and chronic diarrhoea might be conducive to the disease status of AS patients.

In this study, the vocal intonation therapy (VIT) was compared with the standard respiratory therapy for people suffering from respiratory dysfunction as a result of cervical spinal cord injury (CSCI) to observe its effect on vocal quality. Thirty patients with vocal dysfunction after CSCI with the injury time of more than 3 months were screened for inclusion in the trial, and 18 patients completed the 12-weeks, each participant had 60 sessions in total in the clinical trial. All patients were allocated to the intervention group or the control group. The intervention group received VIT training and the control group received respiratory phonation therapy. Both groups were trained by professional therapists, and the training time was 30 min/day, 5 days/week, for 60 sessions for each group in a total of 12 weeks. In the Baseline (T0), mid-intervention period (after 6 weeks, T1), and after intervention (after 12 weeks, T2), the vocal quality of the two groups of patients was tested with a computer-aided real-time audio analyzer 2.1.6 (Adobe Systems, United States) for Sing-SPL (p < 0.0001), Speech-SPL (p < 0.0001), SNL (p < 0.0001), and F0 (p < 0.0001) of the intervention group were significantly improved compared with the control group. In comparing the spectrometry analysis of vocal quality for the 2 groups of participants, there was a significant difference in the results of Sing-SPL and Speech-SPL acoustic analysis in the intervention group of patients at T2 (after 12 weeks) compared to the control group. Vocal intonation therapy—music therapy can improve the speech sound quality of cervical CSCI patients and provide CSCI patients with a practical, highly operable treatment that has both functional training effects and can bring a pleasant experience that can be promoted in the medical field. This study was approved by the Ethics Committee of China Rehabilitation Research Center (CRRC) (approval No. 2019-83-1) on May 20th, 2019. It was registered with the National Health Security Information Platform, medical research registration, and filing information system (Registration No. MR-11-21-011802) on January 28th, 2021.

A novel ultrasonic vibration enhanced friction stir welding (UVeFSW) process was employed to join the rolled 2195 aluminium-lithium alloy of 4 mm thickness. The effects of superimposing ultrasonic on the macro metallograph,microhardness and tensile properties of welded joints were compared and analyzed. The effect of process parameters on the weld formation and joint mechanical properties of aluminium-lithium alloy by ultrasonic vibration enhanced friction stir welding was investigated. The results show that under the same process parameters superimposing ultrasonic energy in friction stir welding can improve the formability of 2195 aluminium-lithium alloy and enhance the plastic material flow in the weld nugget zone, which can reduce or even eliminate the void defect in the conventional friction stir welding joint. The microhardness at the top and middle of the nugget zone increases due to the ultrasonic effect, while the bottom of the weld does not change much. The fracture surfaces of the joints show a ductile fracture mode, and the elongation of the joints increases after ultrasonic vibration energy is applied, and the fracture dimples are more fine and uniform. Under the welding parameters studied the maximum tensile strength and elongation of the joint are 282.8 MPa and 11.5%, respectively. Under the conditions with rotational speed of 600 r/min and welding rate of 225 mm/min, the application of ultrasound can improve the tensile strength and the elongation of the joint by 17.5 MPa and 3.7% respectively.

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

The aim of this study was to provide a new method for dynamic and continuous assessment of ecosystem service value (ESV) and reveal the impact of land use change on ESV in Dasi River Basin within Jinan's startup area from replacing old growth drivers with new ones. Based on four remote sensing images from 2002 to 2020, four ecological indicators were extracted, and the ecological environmental quality index (EEQI) was obtained through the approach of principal component analysis (PCA). Then, the traditional ESV evaluation method was modified by using the EEQI, grain yield, the biomass factor of cropland ecosystem, and the consumer price index (CPI). Finally, the impact of land use change on ESV was further analyzed based on the improved evaluation model. The result showed that (1) during 2002-2020, the area of forestland, grassland, and built-up land showed an increasing trend. The area of cropland and bare land showed a decreasing trend, and the water body area showed a slightly decreasing trend. (2) The total ESV

Background It has been widely accepted that monocytes are one of the central mediators contributing to inflammaging. However, it remains unclear whether aged monocytes, similar to aged T cells, have characteristics of hyperactivation and increased expression of co-inhibitory molecules. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from young (21–40 years old), middle-aged (41–60 years old), and older human subjects (> 60 years old). Flow cytometry was used to monitor changes in the expression of surface molecules of monocyte subsets and cytokine-producing capacity. Results We observed increased tumor necrosis factor-α: TNF-α and decreased interleukin-6 (IL-6) production in monocytes from older adults compared with young and middle-aged adults. Older adults had a greater percentage of intermediate and non-classical monocyte subsets, along with increased levels of the immune activation markers human leukocyte antigen-DR (HLA-DR), and adhesion molecules cluster of differentiation molecule 11b (CD11b) and L-selectin (CD62L). Furthermore, we observed increased C–C motif chemokine receptor 2 (CCR2) expression on classical monocytes and decreased C-X3-C motif chemokine receptor 1 (CX3CR1) expression on non-classical monocytes in older adult subjects. The expression of co-inhibitory receptors was reduced on monocyte subsets in older adults. Conclusions Circulating monocytes in older adults exhibit increased expression of activation, adhesion, and migration markers, but decreased expression of co-inhibitory molecules.

The objectives of this study were to characterize dietary fiber (DF) intake in patients with ankylosing spondylitis (AS), to assess whether DF intake affects disease activity in AS, and to investigate the effect of DF intake on disease activity in AS in the context of functional bowel disease (FBD) symptoms. We recruited 165 patients with AS and divided them into two groups according to whether they had a high DF intake > 25 g/d to investigate the characteristics of people with high DF intake. Some 72 of the 165 AS patients (43%) met the criteria for high DF intake, which was more common in patients with negative FBD symptoms (68%). Data analysis revealed that DF intake was negatively associated with AS disease activity and did not differ statistically significantly from FBD symptoms. Multivariate adjusted models were used to explore the effect of DF intake on AS disease activity. ASDAS-CRP and BASDAI were stable and negatively correlated across models in both groups with and without FBD symptoms. Thus, DF intake positively affected disease activity in patients with AS. ASDAS-CRP and BASDAI were negatively correlated with DF intake.

Yongchun Monascus vinegar is one of famous Chinese vinegar types because of its unique flavor and special bioactivity. Aging process has been regarded as crucial for enhancing the flavor and quality of vinegar. However, changes in the metabolites along the aging of the vinegar are still poorly understood. In this study, a combination of headspace solid-phase micro-extraction gas chromatography-mass spectrometry and chemical isotope labeling liquid chromatography-mass spectrometry methods was used for investigating the metabolomes of one-year-old, five-year-old and thirty-year-old YMVs. DPPH radical-scavenging activity, total phenolics content, and total flavonoids content correlated positively with the aging time. The metabolite compositions in the different-aged vinegars were clearly separated in the PCA analysis. A total of 1133 volatile and non-volatile metabolites changed along the aging; 392 metabolites were in common whereas 126, 84, and 54 changed metabolites were unique to one-to-five year, one-to-thirty year, and five-to-thirty year-old vinegar comparisons, respectively. Organic acids and dipeptides, exhibiting taste characteristics, with constant increase or decrease with aging time and correlated with antioxidant capacities could be used as biomarkers for differentiating the different-aged vinegars. The results revealed aging time related changes in volatile and non-volatile metabolites in YMVs, providing useful knowledge for improving their quality.

Background The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral pharynx in the context of SARS-CoV-2 and other viral infections; hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity. Results We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputa, and 152 fecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load; and microbial community in the upper respiratory tract renders a high risk of antibiotic resistance. Longitudinally, the microbial composition remains relatively stable during the study period. Conclusions Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for the prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, a longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19.

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

Guided bone regeneration (GBR) is an effective alveolar ridge reconstruction technique used before or at implant placement. The combination of various barrier membranes and bone substitutes has been employed. This study aimed to perform a preliminarily evaluation of the safety and performance of a new nonabsorbable bi-layered porous polyethylene (PPE) membrane, in combination with a freeze-dried cortical bone allograft in posterior mandibular ridge augmentation. Fifteen adults who had combined posterior mandibular defects were included for ridge augmentation via GBR using PPE membrane and allograft before implant placement. The keratinized mucosa width (KW), ridge width (RW), ridge height (RH), distance from measurement matrix to bone (DMB), and horizontal alveolar width at 14.0 mm apical to the occlusal plane (HAW) were clinically measured at 15 intended implant sites before and after the augmentation. Fifteen biopsy specimens were harvested at the implant sites for histological analysis. All the subjects completed the whole study. The KW and RH showed minor gains by 0.2 ± 1.4 mm and 0.9 ± 2.3 mm respectively; however, no statistically significant differences were found between, before, and after the augmentation (P > 0.05). In contrast, the RW and HAW significantly increased by 4.8 ± 1.6 mm and 2.3 ± 1.7 mm, respectively, (P ≤ 0.001), while DMB significantly decreased by 1.0 ± 0.8 mm after treatment (P < 0.001). Histological analysis revealed that allograft underwent active bone remodeling. The PPE membrane was adequately safe and efficient to use with allograft in GBR for the reconstruction of combined ridge defects. Although some complications were observed, these were manageable and subsequently lead to successful implant placement for all the subjects. However, further randomized controlled trials are still needed to confirm these findings.

Objective To establish a pig model of inguinal penetrating injury combined with femoral artery hemorrhage, and verify the hemostatic effect of chain-based sponge for the model. Methods The model of inguinal penetrating injury complicated with femoral artery hemorrhage was established with 8 adult Bama mini pigs by muscle transection in inguinal region and perforation of 6 mm femoral artery. The 8 model pigs were randomly and equally divided into two groups. Chain-based hemostatic device (consisted of a disposable push pipe and a compressed polyvinyl alcohol resin sponge) was used for hemostasis of pigs in experimental group. The chain-based sponge were injected into the wound, and the bleeding was compressed after expansion. While in the control group, ordinary gauze was used to fill the wound in a shingle way to stop bleeding. After 3 hours, the hemostatic materials in the two groups were taken out, the survival status of animals in the two groups, the amount of modeled bleeding, the bleeding amount from the start to the end of hemostasis, the time of hemostasis, the total bleeding amount, the time of hemostatic materials removal, and the histopathological findings of muscle tissue at the bottom of the wound and the proximal femoral artery were observed in the two groups. Results The model of inguinal penetrating injury combined with femoral artery hemorrhage was successfully established. All animals in the two groups survived. The hemostasis time was shorter in experimental group than that in control group [(44.3±7.0) s vs. (380.3±23.2) s, P0.05] and the time of hemostatic materials removal between the two groups [(26.3±6.4) s vs. (26.5±5.1) s, P>0.05]. No obvious fracture or necrosis was observed in the muscle tissue of the two groups. The endometrial, medial and outer membranes of the proximal vascular tissue were relatively complete and no obvious necrosis was observed. Conclusions The Bama mini pig model of inguinal penetrating injury combined with femoral artery hemorrhage has the advantages of reliability, efficiency and high repeatability, and can be used for the application research of different hemostatic materials. The chain-based sponge is superior to ordinary gauze in hemostatic time and blood loss, and cause no damage to tissue, so is a good hemostatic device. DOI: 10.11855/j.issn.0577-7402.2019.12.03

Background & AimsTenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug-resistant hepatitis B virus (MDR HBV) and few clinical cases with confirmed TDF-resistance have been reported to date. We reported a quadruple mutant which showed moderate resistant to TDF.Methods and resultsViral rebound was reported in a patient with chronic hepatitis B who underwent TDF monotherapy and harbored a quadruple mutant consisting of classic ETV-resistance mutations (rtL180M/T184L/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M/T184L/A200V/M204V mutant had moderate resistance to TDF treatment, with a 4.52-fold higher half maximal effective concentration than that of wild-type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy.ConclusionAn rtL180M/T184L/A200V/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential NA treatment in a stepwise manner. ETV/TDF combination therapy effectively suppressed replication of this TDF resistant mutant. Our studies provide novel insights into the treatment of NA-naïve patients as well as patients with TDF resistance.

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.

The mutations make uncertain to SARS-CoV-2 disease control and vaccine development. At population-level, single nucleotide polymorphism (SNPs) have displayed mutations for illustrating epidemiology, transmission, and pathogenesis of COVID-19. These mutations are to be expected by the analysis of intra-host level, which presented as intra-host variations (iSNVs). Here, we performed spatio-temporal analysis on iSNVs in 402 clinical samples from 170 patients, and observed an increase of genetic diversity along the day post symptom onset within individual patient and among subpopulations divided by gender, age, illness severity and viral shedding time, suggested a positive selection at intra-host level. The comparison of iSNVs and SNPs displayed that most of nonsynonymous mutations were not fixed suggested a purifying selection. This two-step fitness selection enforced iSNVs containing more nonsynonymous mutations, that highlight the potential characters of SARS-CoV-2 for viral infections and global transmissions.

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.

Intrahost analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences identified 2 viral haplotypes comprised of 3 genetically linked mutations from the respiratory and intestinal tracts of a patient with coronavirus disease 2019. Spatiotemporal data suggest that this patient initially had dual infection of 2 SARS-CoV-2 variants, which subsequently redistributed into the 2 systems.

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.

Singing, as a method of combining respiratory function exercise and vocal intonation therapy, provides a new direction for respiratory function exercise in patients with spinal cord injury. This randomized controlled trial investigated the effects of oral motor respiratory exercise and vocal intonation therapy on respiratory function and vocal quality in patients with spinal cord injury. Among 31 included patients with spinal cord injury, 18 completed the treatment. These 18 patients were randomly assigned to undergo music therapy (intervention group, 30 min/d, 5 times a week, for a total of 12 weeks; n = 9, 7 males and 2 females; 30.33 ± 11.74 years old) or normal respiratory training (control group, n = 9; 8 males and 1 female; 34.78 ± 11.13 years old). Both patient groups received routine treatment concurrently. Before and at 6 and 12 weeks after intervention, a standard respiratory function test, a voice test, the St. George's Respiratory Questionnaire, and a quality of life questionnaire were administered. The results showed that the inspiratory capacity, forced expiratory volume in 1 second, forced vital capacity, maximal mid-expiratory flow rate, sing-loud pressure level, and sustained note length were significantly increased in the intervention group compared with the control group. The St. George's Respiratory Questionnaire and quality of life results of patients in the intervention group were significantly superior to those in the control group. These findings suggest that oral motor respiratory exercise and vocal intonation therapy, as respiratory training methods in music therapy, are effective and valuable for improving respiratory dysfunction and vocal quality in patients with spinal cord injury. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2019-78-1) on May 27, 2019 and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1900026922) on October 26, 2019.