Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China.

Objective: China is among the 30 countries with a high burden of tuberculosis (TB) worldwide, and TB remains a public health concern. Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China. However, molecular epidemiological studies of Kashgar are lacking. Methods: A population-based retrospective study was conducted using whole-genome sequencing (WGS) to determine the characteristics of drug resistance and the transmission patterns. Results: A total of 1,668 isolates collected in 2020 were classified into lineages 2 (46.0%), 3 (27.5%), and 4 (26.5%). The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid (7.4%, 124/1,668), streptomycin (6.0%, 100/1,668), and rifampicin (3.3%, 55/1,668). The rate of rifampicin resistance was 1.8% (23/1,290) in the new cases and 9.4% (32/340) in the previously treated cases. Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains, respectively: 18.6% vs. 8.7 or 9%, P < 0.001. The estimated proportion of recent transmissions was 25.9% (432/1,668). Multivariate logistic analyses indicated that sex, age, occupation, lineage, and drug resistance were the risk factors for recent transmission. Despite the low rate of drug resistance, drug-resistant strains had a higher risk of recent transmission than the susceptible strains (adjusted odds ratio, 1.414; 95% CI, 1.023-1.954; P = 0.036). Among all patients with drug-resistant tuberculosis (DR-TB), 78.4% (171/218) were attributed to the transmission of DR-TB strains. Conclusion: Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

The Latest Research Progress on Cell-Free DNA and Prospects of Its Forensic Application.

In recent years, with the continuous progress of DNA extraction and detection technology, cell-free DNA(cfDNA)has been widely used in the life science field, and its potential application value in forensic identification is becoming more and more obvious. This paper reviews the concept, formation mechanism, and classification of cfDNA, etc., and describes the latest research progress of cfDNA in personal identification of crime scene touch DNA samples and non-invasive prenatal paternity testing (NIPPT). Meanwhile, this paper summarizes the potential application of cfDNA in injury inference, and discusses the advantages and disadvantages of common cfDNA analysis methods and techniques, and its application prospects, to provide a new idea for the wide application of cfDNA in the field of forensic science.

CD4+CD25+ regulatory T cells ex vivo generated from autologous naïve CD4+ T cells suppress EAE progression.

CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4+CD25highCD127low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 104 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS.

Efficacy and safety of agomelatine in epilepsy patients with sleep and mood disorders: An observational, retrospective cohort study.

OBJECTIVE: To evaluate the therapeutic efficacy and safety of agomelatine for treating the sleep and mood disorders in epilepsy patients. METHODS: Retrospective data were derived from 113 epilepsy patients for at least 8 weeks. All the subjects were divided into two groups, one was treated with agomelatine, the other was treated with escitalopram. Their depression and anxiety states were assessed by Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) Scales. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The HAMA, HAMD and PSQI scores in both groups significantly declined after the treatments with agomelatine and escitalopram. However, the agomelatine group exhibited greater improvement in terms of HAMA and PSQI scores compared to the escitalopram group. No severe adverse events were observed in agomelatine group. SIGNIFICANCE: Agomelatine performed better in HAMA and PSQI scores compared to escitalopram, where no significant increase in seizure frequency or side effects were observed. Possibly, agomelatine presents a promising therapeutic option for treating the sleep or mood disorders in epilepsy patients.

The Odorant Receptor Recognizing Camphor in a Camphor Tree Specialist Orthaga achatina (Lepidoptera: Pyralidae).

Camphor has been used as an effective repellent and pesticide to stored products for a long history, but Orthaga achatina (Lepidoptera: Pyralidae) has evolved to specifically feed on the camphor tree Cinnamomum camphora. However, the behavioral response of O. achatina to camphor and the molecular basis of camphor perception are totally unknown. Here, we demonstrated that both male and female adults were behaviorally attracted to camphor, suggesting the adaptation of O. achatina to and utilization of camphor as a signal of C. camphora. Second, in 40 O. achatina OR genes obtained by analyzing antenna transcriptomes, only OachOR16/Orco significantly responded to camphor in the Xenopus oocyte system. Finally, by molecular docking analysis and site-directed mutagenesis, the Ser209 residue is confirmed to be essential for binding of the oachOR16 with camphor. This study not only reveals the camphor-based host plant choice and olfactory mechanisms of O. achatina but also provides a molecular target for screening more potential insect repellents.

Normal sperm head morphometric reference values in fertile Asian males.

ABSTRACT: Sperm head morphology is crucial for male factor infertility diagnosis and assessment of male reproductive potential. Several criteria are available to analyze sperm head morphology, but they are limited by poor methodology comparability and population applicability. This study aimed to explore comprehensive and new normal morphometric reference values for spermatozoa heads in fertile Asian males. An automated sperm morphology analysis system captured 23 152 stained spermatozoa from confirmed fertile males. Of these samples, 1856 sperm head images were annotated by three experienced laboratory technicians as "normal". We employed 14 novel morphometric features to describe sperm head size (head length, head width, length/width ratio, and girth), shape (ellipse intersection over union, girth intersection over union, short-axis symmetry, and long-axis symmetry), area (head, acrosome, postacrosomal areas, and acrosome area ratio), and degrees of acrosome and nuclear uniformity. This straight-forward method for the morphometric analysis of sperm by accurate visual measurements is clinically applicable. The measured parameters present valuable information to establish morphometric reference intervals for normal sperm heads in fertile Asian males. The presented detailed measurement data will be valuable for interlaboratory comparisons and technician training. In vitro fertilization and andrology laboratory technicians can use these parameters to perform objective morphology evaluation when assessing male fertilization potential.

A Pilot Study on Tocilizumab in Very-Late-Onset Myasthenia Gravis.

Objective: This study aimed to initially investigate the efficacy and safety of low-dose tocilizumab combined with glucocorticoid for the treatment of very-late-onset myasthenia gravis (VLOMG). Methods: We conducted a retrospective study in VLOMG patients who were administered intravenous methylprednisolone therapy and subsequently received low-dose oral corticosteroid, in combination with intravenous injection of tocilizumab given once every month for three months. Results: Five patients (mean age 75.0 ± 4.5 years) were included, and all of them were new-onset, and anti-acetylcholine receptor (AChR) antibody-positive generalized MG. The Quantitative Myasthenia Gravis Scale (QMGS) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores before treatment were 15.4 ± 4.3 and 9.6 ± 2.3, respectively, and they exhibited a continuously decreasing trend after the first, second, and third injection of tocilizumab until 6 months after treatment. At 6 months post-treatment, the QMGS and MG-ADL scores were 5.0 ± 2.9 and 2.0 ± 1.2, respectively, and the difference between scores at baseline and 6-month follow-up was significant (P = 0.005 and P < 0.0001, respectively). No serious adverse drug reactions were reported in any patient during the study period. Discussions and Conclusion: The therapeutic efficacy of tocilizumab in VLOMG remains uncertain. The results from our study support the efficacy and safety of this combination treatment option for VLOMG, and strongly suggests the therapeutic potential of tocilizumab in VLOMG. However, considering the limitation of retrospective nature and small sample size in this study, prospective randomized controlled studies including a larger sample size of selected patients are needed to validate our results.

Optical coherence tomography angiography for macular microvessels in ischemic branch retinal vein occlusion treated with conbercept: predictive factors for the prognosis.

AIM: To evaluate the predicative factors of visual prognosis using optical coherence tomography angiography (OCTA) in ischemic branch retinal vein occlusion (BRVO) patients with macular edema (ME) after anti-vascular endothelial growth factor (VEGF) treatment. METHODS: In this retrospective analysis, data from 60 patients (60 eyes) with a definite diagnosis of ischemic BRVO with ME by fundus fluorescein angiography (FFA) were studied. The eyes with ME according to spectral domain optical coherence tomography (SD-OCT) underwent intravitreal conbercept (IVC) and 3+pro re nata (PRN) regimen. The injection times were recorded. Two weeks after injection, fundus laser photocoagulation was performed in the non-perfusion area of the retina. The patients were followed up once a month for 6mo. The best-corrected visual acuity (BCVA), foveal avascular zone (FAZ), and A-circularity index (AI), at 6mo and the baseline were compared. RESULTS: All patients showed significant improvement in BCVA from 0.82±0.32 to 0.39±0.11 logMAR (P<0.001). The mean central macular thickness (CMT) significantly decreased from 476.22±163.54 to 298.66±109.23 µm. Both the FAZ area and AI at 6mo were significantly higher than those at the baseline: the FAZ area increased (0.38±0.02 vs 0.39±0.02 mm2, P<0.05); the AI increased (1.27±0.02 vs 1.31±0.01, P=0.000). The baseline BCVA showed a significantly positive correlation with the baseline FAZ area, FAZ perimeter (PERIM) and AI, final visual gain (FVG) and injection times, respectively (P<0.001). FVG showed a significantly negative correlation with the FAZ area, PERIM, AI and injection times, but a significantly positive correlation with vessel densities (VDs) 300 µm area around FAZ (FD-300; P<0.001). Injection times was positively correlated with the baseline FAZ area, and AI, but inversely correlated with the baseline FD-300 (P<0.001). However macular ischemia was noted in 5 cases during follow-up. CONCLUSION: Using OCTA to observe macular ischemia and quantify parameters can better predict the final visual prognosis of patients before treatment. The changes in FAZ parameters may influence the visual prognosis and injection times.

External quality assessment scheme for sperm DNA fragmentation: a pilot study in China.

BACKGROUND: The aim of this article is to establish an external quality assessment (EQA) scheme for sperm Deoxyribonucleic acid (DNA) fragmentation (SDF) detection, and to assess the feasibility of the scheme. In addition, this article provides some case analysis of abnormal results in order to really help improve the performance of the laboratory. RESULTS: In 2021 and 2022, 10 and 28 laboratories in China volunteered to participate in the EQA program respectively. Two samples were selected for EQA each year, a large spread of results was obtained for the four samples, and the highest values were 13.7, 4.2, 8.0 and 4.0 times the lowest respectively. The coefficients of variation (CVs) were very high for the four samples, at 46.6%, 30.1%, 26.7% and 30.3%, respectively. The CVs of the samples with high SDF values were lower than those of the samples with low SDF values. There was no significant difference between the results of sperm chromatin structure assay (SCSA) and sperm chromatin dispersion (SCD). For the 10 laboratories that participated in EQA in 2021 and 2022, the CVs of low SDF value samples and high SDF value samples decreased from 46.6% and 30.1% in 2021 to 32.5% and 22.7% in 2022, respectively. CONCLUSION: This is the first study to evaluate the EQA program on SDF, which involved a number of laboratories and was demonstrated to be feasible. It is recommended that all laboratories participate in the EQA of SDF to ensure the accuracy of the results.

RéSUMé: CONTEXTES: L'objectif de cet article est d'établir un système externe d'évaluation de la qualité (EEQ) pour la détection de la fragmentation de l'ADN des spermatozoïdes (SDF) et d'évaluer la faisabilité de ce système. En outre, cet article fournit une analyse de cas de résultats anormaux afin d'aider réellement à améliorer les performances du laboratoire. RéSULTATS: En 2021 et 2022, respectivement 10 et 28 laboratoires en Chine se sont portés volontaires pour participer au programme EEQ. Deux échantillons ont été sélectionnés chaque année pour l'EEQ ; un large éventail de résultats a été obtenu pour les quatre échantillons, et les valeurs les plus élevées étaient respectivement de 13,7, 4,2, 8,0 et 4,0 fois les plus faibles. Les coefficients de variation (CV) étaient très élevés pour les quatre échantillons, soit respectivement 46,6 %, 30,1 %, 26,7 % et 30,3 %. Les CV des échantillons avec des valeurs de SDF élevées étaient inférieurs à ceux des échantillons avec de faibles valeurs de SDF. Il n'y avait pas de différence significative entre les résultats du test de structure de la chromatine des spermatozoïdes (SCSA) et ceux de la dispersion de la chromatine des spermatozoïdes (SCD). Pour les 10 laboratoires qui ont participé à l'EEQ en 2021 et 2022, les CV des échantillons à faible valeur de SDF et ceux des échantillons à valeur élevée de SDF ont diminué, passant respectivement de 46,6 % et 30,1 % en 2021 à 32,5 % et 22,7 % en 2022. CONCLUSIONS: Il s'agit de la première étude à évaluer le programme externe d'évaluation de la qualité (EEQ) de l'analyse de la SDF, qui a impliqué un certain nombre de laboratoires, et qui s'est avéré réalisable. Il est recommandé que tous les laboratoires participent à l'EEQ de la SDF afin d'en assurer l'exactitude des résultats.

Ginkgolide attenuates memory impairment and neuroinflammation by suppressing the NLRP3/caspase-1 pathway in Alzheimer's disease.

The NLRP3 inflammasome is involved in the neuroinflammatory pathway of Alzheimer's disease (AD). The aim of this study is to explore the roles and underlying mechanisms of ginkgolide (Baiyu®) on amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and a murine microglial cell line, BV-2. In the present study, the APP/PS1 mice were administered with ginkgolide, followed by a Morris water maze test. The mice were then euthanized to obtain brain tissue for histological and Aß analysis. Additionally, BV-2 cells were pretreated with ginkgolide and then incubated with Aß1-42 peptide. NLRP3, ASC, and caspase-1 mRNA and protein expression in brain tissue of mice and BV-2 cells were quantified by real-time PCR and western blotting, as well as reactive oxygen species (ROS) production, interleukin (IL)-1ß and IL-18 levels by lucigenin technique and ELISA. Compared with the APP/PS1 mice, ginkgolide-treated mice demonstrated the shortened escape latency, reduced plaques, less inflammatory cell infiltration and neuron loss in the hippocampi of APP/PS1 mice. The levels of NLRP3, ASC, caspase-1, ROS, IL-1ß, and IL-18 were also decreased in the brain tissue of APP/PS1 mice or Aß1-42-treated BV-2 cells following ginkgolide treatment. Ginkgolide exerted protective effects on AD, at least partly by inactivating the NLRP3/caspase-1 pathway.

The effect of dipeptidyl peptidase-4 inhibitor on incidence and clinical course in bullous pemphigoid patients in a tertiary medical center.

Several studies have reported an association between dipeptidyl peptidase 4 inhibitor (DPP4i), a commonly prescribed second-line oral antihyperglycemic drug, and bullous pemphigoid (BP). However, the benefits of DPP4i withdrawal in patients with BP remain controversial. This study primarily aimed to evaluate the clinical severity of DPP4i-associated BP by comparing it to those without Type 2 diabetes mellitus (DM). The secondary objective was to determine whether cessation of DPP4i is necessary for all patients with BP. This retrospective case-control study included 83 patients. The participants were divided into three groups according to their diabetic status and the status of discontinuance or continuance of DPP4i. The 12-month follow-up of the monthly dosage of systemic steroids per body weight (kg) and the percentage of systemic steroid off-therapy in these participants were recorded since the diagnosis of BP. Compared to patients with BP without DM, the 1st, 3rd, and 12th systemic prednisolone doses were significantly lower in the DPP4i group (p = 0.01684, 0.02559, and 0.009336, respectively). The 12th systemic prednisolone dose was significantly lower in patients who discontinued DPP4i (p = 0.0338). Nevertheless, several spontaneous remissions with systemic steroid off-therapy were also noted in the DPP4i-continuance group within 12 months of follow-up. This article supports the favorable impact of DPP4i withdrawal in patients with BP and shows that DPP4i may incite or aggravate BP, resulting in a milder disease course.

Effects of Preoperative High-Intensity Interval Training Combined With Team Empowerment Education in Lung Cancer Patients With Surgery: A Quasi-experimental Trial.

BACKGROUND: Cancer itself and surgery put a heavy burden on lung cancer patients, physiologically and psychologically. Enhancing self-efficacy during high-intensity interval training is essential for achieving the full benefit of pulmonary rehabilitation in lung cancer patients. OBJECTIVE: This study aimed to explore the effects of high-intensity interval training combined with team empowerment education on patients with lung resection. METHODS: This is a quasi-experimental trial with a pretest-posttest design. Participants were assigned to one of the 3 groups according to the order of admission: (1) combined intervention group, (2) intervention group, or (3) routine care group. The outcome measures included dyspnea, exercise capacity, exercise self-efficacy, anxiety, depression, postoperative indwelling time of thoracic drainage tube, and total in-hospital stay. RESULTS: Per-protocol results showed that dyspnea, exercise capacity, exercise self-efficacy, anxiety, and depression of the patients in the combined intervention group were significantly improved. However, no significant difference was observed in postoperative indwelling time of thoracic drainage tube or total in-hospital stay among the 3 groups. CONCLUSION: This hospital-based short-term high-intensity interval training combined with team empowerment education for lung cancer patients undergoing surgery was safe and feasible, indicating this program can be a promising strategy to manage perioperative symptoms. IMPLICATIONS FOR PRACTICE: This study provides evidence supporting preoperative high-intensity interval training as a promising method to make the best use of preoperative time, thus improving adverse symptoms in lung cancer patients undergoing surgery, and also provides a new strategy to raise exercise self-efficacy and promote patients' rehabilitation.

[Construction of cell factories for production of patchoulol in Saccharomyces cerevisiae].

Patchoulol is an important sesquiterpenoid in the volatile oil of Pogostemon cablin, and is also considered to be the main contributing component to the pharmacological efficacy and fragrance of P. cablin oil, which has antibacterial, antitumor, antioxidant, and other biological activities. Currently, patchoulol and its essential oil blends are in high demand worldwide, but the traditional plant extraction method has many problems such as wasting land and polluting the environment. Therefore, there is an urgent need for a new method to produce patchoulol efficiently and at low cost. To broaden the production method of patchouli and achieve the heterologous production of patchoulol in Saccharomyces cerevisiae, the patchoulol synthase(PS) gene from P. cablin was codon optimized and placed under the inducible strong promoter GAL1 to transfer into the yeast platform strain YTT-T5, thereby obtaining strain PS00 with the production of(4.0±0.3) mg·L~(-1) patchoulol. To improve the conversion rate, this study used protein fusion method to fuse SmFPS gene from Salvia miltiorrhiza with PS gene, leading to increase the yield of patchoulol to(100.9±7.4) mg·L~(-1) by 25-folds. By further optimizing the copy number of the fusion gene, the yield of patchoulol was increased by 90% to(191.1±32.7) mg·L~(-1). By optimizing the fermentation process, the strain was able to achieve a patchouli yield of 2.1 g·L~(-1) in a high-density fermentation system, which was the highest yield so far. This study provides an important basis for the green production of patchoulol.

Response predictor for pigment reduction after one session of photo-based therapy using convolutional neural network: A proof of concept study.

BACKGROUND: Identifying treatment responders after a single session of photo-based procedure for hyperpigmentary disorders may be difficult. OBJECTIVES: We aim to train a convolutional neural network (CNN) to test the hypothesis that there exist discernible features in pretreatment photographs for identifying favorable responses after photo-based treatments for facial hyperpigmentation and develop a clinically applicable algorithm to predict treatment outcome. METHODS: Two hundred and sixty-four sets of pretreatment photographs of subjects receiving photo-based treatment for esthetic enhancement were obtained using the VISIA® skin analysis system. Preprocessing was done by masking the facial features of the photographs. Each set of photographs consists of five types of images. Five independently trained CNNs based on the Resnet50 backbone were developed based on these images and the results of these CNNs were combined to obtain the final result. RESULTS: The developed CNN algorithm has a prediction accuracy approaching 78.5% with area under the receiver operating characteristic curve being 0.839. CONCLUSION: The treatment efficacy of photo-based therapies on facial skin pigmentation can be predicted based on pretreatment images.

16α-OHE1, a novel oestrogen metabolite, attenuates dysfunction of left ventricle contractility via regulation of autophagy after myocardial ischemia and reperfusion.

BACKGROUND: Myocardial ischemia-reperfusion (MI/R) can exacerbate the initial cardiac damage in the myocardial functional changes, including dysfunction of left ventricular contractility. Oestrogen has been proven to protect the cardiovascular system. However, whether the oestrogen or its metabolites play the main role in attenuating dysfunction of left ventricular contractility is unknown. METHODS AND RESULTS: This study used the LC-MS/MS to detect oestrogen and its metabolites in clinical serum samples (n = 62) with heart diseases. After correlation analysis with markers of myocardial injury including cTnI (P < 0.01), CK-MB (P < 0.05), and D-Dimer (P < 0.001), 16α-OHE1 was identified. The result from LC-MS/MS in female and ovariectomised (OVX) rat serum samples (n = 5) matched the findings in patients. In MI/R model of animal, the recovery of left ventricular developed pressure (LVDP), rate pressure product (RPP), dp/dtmax and dp/dtmin after MI/R in OVX or male group were worsened than those in female group. Also, the infarction area of OVX or male group was larger than that in females (n = 5, p < 0.01). Furthermore, LC3 II in the left ventricle of OVX and male group was lower than that in females (n = 5, p < 0.01) by immunofluorescence. In H9C2 cells, after the application of 16α-OHE1, the number of autophagosomes was further increased and other organelles improved in MI/R. Simultaneously, LC3 II, Beclin1, ATG5, and p-AMPK/AMPK were increased, and p-mTOR/mTOR was decreased (n = 3, p < 0.01) by Simple Western. CONCLUSION: 16α-OHE1 could attenuate left ventricle contractility dysfunction via autophagy regulation after MI/R, which also offered fresh perspectives on therapeutical treatment for attenuating MI/R injury.

Effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

AIM: To investigate the effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eight electronic databases including PubMed, Web of Science, Cochrane library, Embase, CINAHL, China National Knowledge Infrastructure, Wangfang and Weipu databases were systematically searched from inception of the database to January 10, 2022. METHODS: Statistical analysis was performed using Review Manager 5.4 and results were reported as mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CI). Outcomes were the forced expiratory volume in 1 second (FEV1), forced volume capacity (FVC) and percent of FEV1/FVC. The Cochrane Risk of Bias Tool was used to assess the risk of bias of included studies. The study protocol was not registered. RESULTS: Eight randomized controlled trials (RCTs) including 476 participants met the inclusion criteria and were included in meta-analysis. It was found that internet-based self-management interventions showed a significant improvement in FVC(L), while FEV1 (%), FEV1 (L), FEV1/FVC (%) and FVC (%) did not significantly improve. CONCLUSIONS: Internet-based self-management interventions were effective in improving pulmonary function in patients with COPD, caution should be exercised in interpreting the results. RCTs of higher quality are needed in the future to further demonstrate the effectiveness of the intervention. RELEVANCE TO CLINICAL PRACTICE: It provides evidence for internet-based self-management interventions in improving pulmonary function in patients with COPD. IMPACT: The results suggested that internet-based self-management interventions could improve the pulmonary function in people with COPD. This study provides a promising alternative method for patients with COPD who have difficulty seeking face-to-face self-management interventions, and the intervention can be applied in clinical settings. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Ependyma in Neurodegenerative Diseases, Radiation-Induced Brain Injury and as a Therapeutic Target for Neurotrophic Factors.

The neuron loss caused by the progressive damage to the nervous system is proposed to be the main pathogenesis of neurodegenerative diseases. Ependyma is a layer of ciliated ependymal cells that participates in the formation of the brain-cerebrospinal fluid barrier (BCB). It functions to promotes the circulation of cerebrospinal fluid (CSF) and the material exchange between CSF and brain interstitial fluid. Radiation-induced brain injury (RIBI) shows obvious impairments of the blood-brain barrier (BBB). In the neuroinflammatory processes after acute brain injury, a large amount of complement proteins and infiltrated immune cells are circulated in the CSF to resist brain damage and promote substance exchange through the BCB. However, as the protective barrier lining the brain ventricles, the ependyma is extremely vulnerable to cytotoxic and cytolytic immune responses. When the ependyma is damaged, the integrity of BCB is destroyed, and the CSF flow and material exchange is affected, leading to brain microenvironment imbalance, which plays a vital role in the pathogenesis of neurodegenerative diseases. Epidermal growth factor (EGF) and other neurotrophic factors promote the differentiation and maturation of ependymal cells to maintain the integrity of the ependyma and the activity of ependymal cilia, and may have therapeutic potential in restoring the homeostasis of the brain microenvironment after RIBI or during the pathogenesis of neurodegenerative diseases.

Characterization of antigen-specific CD8+ memory T cell subsets in peripheral blood of patients with multiple sclerosis.

Background: Increasing evidence indicates the importance of CD8+ T cells in autoimmune attack against CNS myelin and axon in multiple sclerosis (MS). Previous research has also discovered that myelin-reactive T cells have memory phenotype functions in MS patients. However, limited evidence is available regarding the role of CD8+ memory T cell subsets in MS. This study aimed to explore potential antigen-specific memory T cell-related biomarkers and their association with disease activity. Methods: The myelin oligodendrocyte glycoprotein (MOG)-specific CD8+ memory T cell subsets and their related cytokines (perforin, granzyme B, interferon (IFN)-γ) and negative co-stimulatory molecules (programmed cell death protein 1 (PD-1), T- cell Ig and mucin domain 3 (Tim-3)) were analyzed by flow cytometry and real-time PCR in peripheral blood of patients with relapsing-remitting MS. Results: We found that MS patients had elevated frequency of MOG-specific CD8+ T cells, MOG-specific central memory T cells (TCM), MOG-specific CD8+ effector memory T cells (TEM), and MOG-specific CD8+ terminally differentiated cells (TEMRA); elevated granzyme B expression on MOG-specific CD8+ TCM; and, on MOG-specific CD8+ TEM, elevated granzyme B and reduced PD-1 expression. The Expanded Disability Status Scale score (EDSS) in MS patients was correlated with the frequency of MOG-specific CD8+ TCM, granzyme B expression in CD8+ TCM, and granzyme B and perforin expression on CD8+ TEM, but with reduced PD-1 expression on CD8+ TEM. Conclusion: The dysregulation of antigen-specific CD8+ memory T cell subsets, along with the abnormal expression of their related cytokines and negative co-stimulatory molecules, may reflect an excessive or persistent inflammatory response induced during early stages of the illness. Our findings strongly suggest positive regulatory roles for memory T cell populations in MS pathogenesis, probably via molecular mimicry to trigger or promote abnormal peripheral immune responses. Furthermore, downregulated PD-1 expression may stimulate a positive feedback effect, promoting MS-related inflammatory responses via the interaction of PD-1 ligands. Therefore, these parameters are potential serological biomarkers for predicting disease development in MS.