TERT activation targets DNA methylation and multiple aging hallmarks.

Insufficient telomerase activity, stemming from low telomerase reverse transcriptase (TERT) gene transcription, contributes to telomere dysfunction and aging pathologies. Besides its traditional function in telomere synthesis, TERT acts as a transcriptional co-regulator of genes pivotal in aging and age-associated diseases. Here, we report the identification of a TERT activator compound (TAC) that upregulates TERT transcription via the MEK/ERK/AP-1 cascade. In primary human cells and naturally aged mice, TAC-induced elevation of TERT levels promotes telomere synthesis, blunts tissue aging hallmarks with reduced cellular senescence and inflammatory cytokines, and silences p16INK4a expression via upregulation of DNMT3B-mediated promoter hypermethylation. In the brain, TAC alleviates neuroinflammation, increases neurotrophic factors, stimulates adult neurogenesis, and preserves cognitive function without evident toxicity, including cancer risk. Together, these findings underscore TERT's critical role in aging processes and provide preclinical proof of concept for physiological TERT activation as a strategy to mitigate multiple aging hallmarks and associated pathologies.

Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth.

Glioblastoma stem cells (GSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. To illuminate mechanisms governing these hallmark features, we developed a de novo glioblastoma multiforme (GBM) model derived from immortalized human neural stem/progenitor cells (hNSCs) to enable precise system-level comparisons of pre-malignant and oncogene-induced malignant states of NSCs. Integrated transcriptomic and epigenomic analyses uncovered a PAX6/DLX5 transcriptional program driving WNT5A-mediated GSC differentiation into endothelial-like cells (GdECs). GdECs recruit existing endothelial cells to promote peritumoral satellite lesions, which serve as a niche supporting the growth of invasive glioma cells away from the primary tumor. Clinical data reveal higher WNT5A and GdECs expression in peritumoral and recurrent GBMs relative to matched intratumoral and primary GBMs, respectively, supporting WNT5A-mediated GSC differentiation and invasive growth in disease recurrence. Thus, the PAX6/DLX5-WNT5A axis governs the diffuse spread of glioma cells throughout the brain parenchyma, contributing to the lethality of GBM.

Factors associated with nocturnal and diurnal glycemic variability in patients with type 2 diabetes: a cross-sectional study.

PURPOSE: There is little information on factors that influence the glycemic variability (GV) during the nocturnal and diurnal periods. We aimed to examine the relationship between clinical factors and GV during these two periods. METHODS: This cross-sectional study included 134 patients with type 2 diabetes. 24-h changes in blood glucose were recorded by a continuous glucose monitoring system. Nocturnal and diurnal GV were assessed by standard deviation of blood glucose (SDBG), coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE), respectively. Robust regression analyses were performed to identify the factors associated with GV. Restricted cubic splines were used to determine dose-response relationship. RESULTS: During the nocturnal period, age and glycemic level at 12:00 A.M. were positively associated with GV, whereas alanine aminotransferase was negatively associated with GV. During the diurnal period, homeostatic model assessment 2-insulin sensitivity (HOMA2-S) was positively associated with GV, whereas insulin secretion-sensitivity index-2 (ISSI2) was negatively associated with GV. Additionally, we found a J-shape association between the glycemic level at 12:00 A.M. and MAGE, with 9.0 mmol/L blood glucose level as a cutoff point. Similar nonlinear associations were found between ISSI2 and SDBG, and between ISSI2 and MAGE, with ISSI2 value of 175 as a cutoff point. CONCLUSION: Factors associated with GV were different between nocturnal and diurnal periods. The cutoff points we found in this study may provide the therapeutic targets for beta-cell function and pre-sleep glycemic level in clinical practice.

[Association, differences, and applications of three commonly used statistical indicators: risk ratio, hazard ratio, and odds ratio].

Relative Risk (RR), Hazard Ratio (HR), and Odds Ratio (OR) are commonly used statistical measures in the field of public health to assess the magnitude of the effect of exposure factors on outcomes. These indicators have different calculation principles and implications in public health. However, a few researchers misused or misinterpreted RR, HR, and OR values when interpreting study results. Therefore, this article explores the relationships and differences among these measures, as well as the correct selection and application of RR, HR, and OR in both cohort study and case-control study.

Long Noncoding RNA RUNXOR Promotes Myeloid-Derived Suppressor Cell Expansion and Functions via Enhancing Immunosuppressive Molecule Expressions during Latent HIV Infection.

RUNX1 overlapping RNA (RUNXOR) is a long noncoding RNA and a key regulator of myeloid-derived suppressor cells (MDSCs) via targeting runt-related transcription factor 1 (RUNX1). We and others have previously reported MDSC expansion and inhibition of host immune responses during viral infections; however, the mechanisms regulating MDSC differentiation and suppressive functions, especially the role of RUNXOR-RUNX1 in the regulation of MDSCs in people living with HIV (PLHIV), remain unknown. In this study, we demonstrate that RUNXOR and RUNX1 expressions are upregulated in MDSCs that expand and accumulate in human PBMCs derived from PLHIV. We found that the upregulation of RUNXOR and RUNX1 is associated with the expressions of several key immunosuppressive molecules, including arginase 1, inducible NO synthase, STAT3, IL-6, and reactive oxygen species. RUNXOR and RUNX1 could positively regulate each other's expression and control the expressions of these suppressive mediators. Specifically, silencing RUNXOR or RUNX1 expression in MDSCs from PLHIV attenuated MDSC expansion and immunosuppressive mediator expressions, whereas overexpressing RUNXOR in CD33+ myeloid precursors from healthy subjects promoted their differentiation into MDSCs and enhanced the expression of these mediators. Moreover, loss of RUNXOR-RUNX1 function in MDSCs improved IFN-γ production from cocultured autologous CD4 T cells derived from PLHIV. These results suggest that the RUNXOR-RUNX1 axis promotes the differentiation and suppressive functions of MDSCs via regulating multiple immunosuppressive signaling molecules and may represent a potential target for immunotherapy in conjunction with antiviral therapy in PLHIV.

Eosinophilic fasciitis in a young male auto mechanic exposed to organic solvents.

We report a case of eosinophilic fasciitis in a teenage auto mechanic who was most likely affected by occupational exposure to organic solvents, including the aromatic hydrocarbons benzene, trimethylbenzene, naphthalene, toluene, and xylene. The patient presented with an 8-month history of painful induration of his extremities and an abnormal gait. A deep excisional biopsy of the fascia was obtained, demonstrating subcutaneous fibrosis with perivascular and interstitial inflammation, with lymphocytes and plasma cells spilling into the sclerosed fascia, and focal fibrinoid necrosis. Treatment was begun with intravenous pulse doses of methylprednisolone, prednisone (20 mg daily), and subcutaneous methotrexate (25 mg weekly), and the patient's painful induration had resolved and gait had normalized at the 6-month follow-up. Our case suggests that exposure to organic solvents could be implicated in the pathogenesis of eosinophilic fasciitis and highlights the importance of a thorough occupational history to prevent repeat exposures to potentially causative agents.

[Pathologic features of paraspinal muscle biopsies in patients with adolescent idiopathic scoliosis].

OBJECTIVE: To characterize the paraspinal muscles of adolescent idiopathic scoliosis (AIS) patients, and to further explore its etiology. METHODS: Clinical records and paraspinal muscle biopsies at the apex vertebra region during posterior scoliosis correction surgery of 18 AIS were collected from November 2018 to August 2019. Following standardized processing of fresh muscle tissue biopsy, serial sections with conventional hematoxylin-eosin (HE) and histochemical and immunohistochemical (IHC) with antibody Dystrophin-1 (R-domain), Dystrophin-2 (C-terminal), Dystrophin-3 (N-terminal), Dystrophin-total, Myosin (fast), major histocompatibility complex 1 (MHC-1), CD4, CD8, CD20, and CD68 staining were obtained. Biopsy samples were grouped according to the subjects' median Cobb angle (Cobb angle ≥ 55° as severe AIS group and Cobb angle < 55° as mild AIS group) and Nash-Moe's classification respectively, and the corresponding pathological changes were compared between the groups statistically. RESULTS: Among the 18 AIS patients, 8 were in the severe AIS group (Cobb angle ≥55°) and 10 in the mild AIS group (Cobb angle < 55°). Both severe and mild AIS groups presented various of atrophy and degeneration of paraspinal muscles, varying degrees and staining patterns of immune-expression of Dystrophin-3 loss, especially Dystrophin-2 loss in severe AIS group with significant differences, as well as among the Nash-Moe classification subgroups. Besides, infiltration of CD4+ and CD8+ cells in the paraspinal muscles and tendons was observed in all the patients while CD20+ cells were null. The expression of MHC-1 on myolemma was present in some muscle fibers. CONCLUSION: The histologic of paraspinal muscle biopsy in AIS had similar characteristic changes, the expression of Dystrophin protein was significantly reduced and correlated with the severity of scoliosis, suggesting that Dystrophin protein dysfunctions might contribute to the development of scoliosis. Meanwhile, the inflammatory changes of AIS were mainly manifested by T cell infiltration, and there seemed to be a certain correlation between inflammatory cell infiltration, MHC-1 expression and abnormal expression of Dystrophin. Further research along the lines of this result may open up new ideas for the diagnosis of scoliosis and the treatment of paraspinal myopathy.

[Anti-HMGCR immune-mediated necrotizing myopathy: A case report].

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.

[Recent progress in the treatment of intractable sialolithiasis].

Sialolithiasis occurs in approximately 0.45% to 1.20% of the general population. The typical clinical symptom manifests as a painful swelling of the affected glands after a meal or upon salivary stimulation, which extremely affects the life quality of the patients. With the development of sialendoscopy and lithotripsy, most sialoliths can be successfully removed with preservation of the gland. However, sialoliths in the deep hilar-parenchymal submandibular ducts and impacted parotid stones located in the proximal ducts continue to pose great challenges. Our research center for salivary gland diseases (in Peking University School and Hospital of Stomatology) has used sialendoscopy for 17 years and treated >2 000 patients with salivary gland calculi. The success rate was approximately 92% for submandibular gland calculi and 95% for parotid calculi. A variety of minimally invasive surgical techniques have been applied and developed, which add substantial improvements in the treatment of refractory sialolithiasis. Further, the radiographic positioning criteria and treatment strategy are proposed for these intractable stones. Most of the hilar-parenchymal submandibular stones are successfully removed by a transoral approach, including transoral duct slitting and intraductal basket grasping, while a small portion of superficial stones can be removed by a mini-incision in submandibular area. Impacted stones located in the distal third of parotid gland ducts are removed via "peri-ostium incision", which is applied to avoid a cicatricial stenosis from a direct ostium incision. Impacted parotid stones located in the middle and proximal third of the Stensen's duct are removed via a direct mini-incision or a peri-auricular flap. A direct transcutaneous mini-incision is commonly performed under local anesthesia with an imperceptible scar, and is indicated for most of impacted stones located in the middle third, hilum and intraglandular ducts. By contrast, a peri-auricular flap is performed under general anesthesia with relatively larger operational injury of the gland parenchyma, and should be best reserved for deeper intraglandular stones. Laser lithotripsy has been applied in the treatment of sialolithiasis in the past decade, and holmium ∶YAG laser is reported to have the best therapeutic effects. During the past 3 years, our research group has performed laser lithotripsy for a few cases with intractable salivary stones. From our experiences, withdrawal of the endoscopic tip 0.5-1.0 cm away from the extremity of the laser fiber, consistent saline irrigation, and careful monitoring of gland swelling are of vital importance for avoidance of injuries of the ductal wall and the vulnerable endoscope lens during lithotripsy. Larger calculi require multiple treatment procedures. The risk of ductal stenosis can be alleviated by endoscopic dilation. In summary, appropriate use of various endoscopy-assisted lithotomy helps preserve the gland function in most of the patients with refractory sialolithiasis. Further studies are needed in the following aspects: Transcervical removal of intraglandular submandibular stones, intraductal laser lithotripsy of impacted parotid stones and deep submandibular stones, evaluation of long-term postoperative function of the affected gland, et al.

[Efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis].

Objective: To explore the efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis. Methods: A cohort study. The clinical data of patients with refractory chronic gouty arthritis who were treated with rasburicase at Sun Yat-sen Memorial Hospital, Sun Yat-sen University between January 2021 and July 2022 were retrospectively analyzed. Refractory chronic gouty arthritis was defined as serum uric acid (sUA)>360 µmol/L and urate volume>10 cm3 under dual-energy computed tomography after tolerable maximal oral urate-lowering therapy for at least 3 months. The administration of low-dose rasburicase was applied intravenously with total dosage ranging from 4.5 to 7.5 mg each dose, at 4-week intervals for a maximum of three doses. Efficacy was evaluated by the changes of sUA level, tophus and urate volume. Results: A total of 22 patients were included for analysis, with 95.4% (21/22) male, the mean age was (44±15) years, and the median duration of gout was 11 (6-15) years. The mean sUA at baseline was (667±112) µmol/L. The levels of sUA significantly decreased after each dose of rasburicase (P<0.001), and the median reduction of sUA after each dose of rasburicase was 568 (471-635), 187 (66-335) and 123 (49-207) µmol/L, respectively. At week 12, nine patients (40.9%) exhibited sUA<360 µmol/L and tophus disappeared in one patient. The urate volume significantly decreased at week 12 when compared with that before the first dose of rasburicase in all the patients [40 (16-172) cm3 vs 17 (7-134) cm3, P<0.001], with a median reduction rate of 41.6% (22.9%-58.5%). The everall safety of rasburicase was good, and no serious adverse reactions occurred. Conclusions: Low-dose rasburicase is well-tolerated and effective for decreasing the urate burden in patients with refractory chronic gouty arthritis. Further prospective randomized controlled trials are needed to validate these findings.

[In vitro activity of ß-lactamase inhibitors avibanvctam and relebactam in combination with ß-lactams against multidrug-resistant Mycobacterium tuberculosis and mutations of resistance genes].

Objective: To evaluate the activity of six ß-lactams in combination with three ß-lactamase inhibitors against mycobacterium tuberculosis(MTB) in vitro. Methods: A total of 105 multidrug-resistant tuberculosis (MDR-TB) strains from different regions of Henan province from January to September 2020 were included in this study. Drug activity of six ß-lactams (biapenem, meropenem, imipenem, doripenem, ertapenem and tebipenem) alone or in combination with ß-lactamase inhibitors (clavulanic acid, avibactam and relebactam) was examined by minimum inhibitory concentration method (MICs) against 105 clinical isolates. Mutations of blaC, ldtmt1 and ldtmt2 were analyzed by PCR and DNA sequencing. Chi-square test was used to compare the antimicrobial activities of different ß-lactam drugs. Results: Out of the ß-lactams used herein, tebipenem was the most effective against MDR-TB and had an MIC50 value of 8 mg/L(χ2=123.70,P=0.001). Besides, after the addition of ß-lactamase inhibitors, the MICs of most ß-lactam drugs were reduced more evidently in the presence of avibactam and relebactam compared to clavulanic acid.Especially, relebactam decreased both the MIC50 and MIC90 of telbipenem by 16-fold, and diluted the MIC of 23 (21.90%) and 41 (39.04%) isolatesby 32-fold and 16-fold.In addition, a total of 13.33% (14/105) of isolates harbored mutations in the blaC gene, with three different nucleotide substitutions: AGT333AGG, AAC638ACC and ATC786ATT. For the strains with Ser111Arg and Asn213Thr substitution in BlaC, the MIC values of the meropenem-clavulanate combination were reduced compared with a synonymous single nucleotide polymorphism (SNP) group. Conclusions: Both avibactam and relebactam had better synergistic effects on ß-lactams than clavulanic acid. The combination of tebipenem and relebactam showed the most potent activity against MDR-TB isolates. In addition, the Ser111Arg and Asn213Thr substitution of BlaC may be associated with an increased susceptibility of MDR-TB isolates to meropenem in the presence of clavulanate.

Probing Operator Spreading via Floquet Engineering in a Superconducting Circuit.

Operator spreading, often characterized by out-of-time-order correlators (OTOCs), is one of the central concepts in quantum many-body physics. However, measuring OTOCs is experimentally challenging due to the requirement of reversing the time evolution of systems. Here we apply Floquet engineering to investigate operator spreading in a superconducting 10-qubit chain. Floquet engineering provides an effective way to tune the coupling strength between nearby qubits, which is used to demonstrate quantum walks with tunable couplings, reversed time evolution, and the measurement of OTOCs. A clear light-cone-like operator propagation is observed in the system with multiple excitations, and has a nearly equal velocity as the single-particle quantum walk. For the butterfly operator that is nonlocal (local) under the Jordan-Wigner transformation, the OTOCs show distinct behaviors with (without) a signature of information scrambling in the near integrable system.

Aetiology of tinea capitis in China: a multicentre prospective study.

BACKGROUND: Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time. OBJECTIVES: This study aimed to clarify the current epidemiological characteristics and pathogen spectrum of tinea capitis in China. METHODS: A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory. RESULTS: Among all enrolled patients, 74·1% of the cases were in patients aged 2-8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province. CONCLUSIONS: Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.

Sex-specific metabolic risk factors and their trajectories towards the non-alcoholic fatty liver disease incidence.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease. This study examined sex-specific associations between NAFLD and metabolic factors and investigated the trajectory of risk factors. METHODS: We retrospectively investigated 16,140 individuals from Beijing Health Management Cohort. Univariate and multivariate time-dependent Cox regression analyses were performed to identify independent risk factors for new-onset NAFLD. The trajectory of risk factors was investigated using the latent growth curve model and growth mixture model. RESULTS: Over a median follow-up of 3.15 years, 2,450 (15.18%) participants developed NAFLD. The risk factors for NAFLD in men were increased body mass index (BMI); waist circumference (WC); triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), haemoglobin (Hb), and serum uric acid (SUA) levels; and platelet (PLT) count and decreased serum creatinine-to-body weight (sCr/bw) and high-density lipoprotein cholesterol (HDL-C) levels. In women, the risk factors were increased BMI, WC, and fasting plasma glucose (FPG), TG, LDL-C, SUA, white blood cell (WBC), and PLT and decreased sCr/bw and HDL-C levels. In addition, BMI, LDL-C, sCr/bw and PLT changing trajectories were associated with NAFLD in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends was associated with NAFLD risk in women. CONCLUSIONS: Development of NAFLD is associated with BMI, LDL-C, sCr/bw and PLT changing trajectories in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends are associated an increased risk of NAFLD in women. Deterioration of metabolic risk factors status can be a predictor of NAFLD many years before its occurrence.

Semantic intrusion errors as a function of age, amyloid, and volumetric loss: a confirmatory path analysis.

OBJECTIVE: To examine the direct and indirect effects of age, APOE ϵ4 genotype, amyloid positivity, and volumetric reductions in AD-prone brain regions as it relates to semantic intrusion errors reflecting proactive semantic interference (PSI) and the failure to recover from proactive semantic interference (frPSI) on the Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), a cognitive stress test that has been consistently more predictive of preclinical and prodromal Alzheimer's disease (AD) than traditional list-learning tests. DESIGN: Cross-sectional study. SETTING: 1Florida Alzheimer's Disease Research Center baseline study. PARTICIPANTS: Two-hundred and twelve participants with Mini-Mental State Examination (MMSE) score above 16 and a broad array of cognitive diagnoses ranging from cognitively normal (CN) to dementia, of whom 58% were female, mean age of 72.1 (SD 7.9). MEASURES: Participants underwent extensive clinical and neuropsychological evaluations, MR and amyloid Positron Emission Tomography/Computer/Computer Tomography (PET/CT) imaging, and analyses of APOE ϵ4 genotype. Confirmatory path analyses were conducted in the structural equation modeling framework that estimated multiple equations simultaneously while controlling for important covariates such as sex, education, language of evaluation, and global cognitive impairment. RESULTS: Both amyloid positivity and decreased brain volumes in AD-prone regions were directly related to LASSI-L Cued B1 and Cued B2 intrusions (sensitive to PSI and frPSI effects) even after controlling for covariates. APOE ϵ4 status did not evidence direct effects on these LASSI-L cognitive markers, but rather exerted their effects on amyloid positivity, which in turn related to PSI and frPSI. Similarly, age did not have a direct relationship with LASSI-L scores, but exerted its effects indirectly through amyloid positivity and volumes of AD-prone brain regions. CONCLUSIONS: Our study provides insight into the relationships among age, APOE ϵ4, amyloid, and brain volumetric reductions as it relates to semantic intrusion errors. The investigation expands our understanding of the underpinnings of PSI and frPSI intrusions in a large cohort.

[Management of the nondisplaced type Herbert D1 scaphoid fracture with robot navigation combined with wrist arthroscopy].

To investigate the feasibility and the clinical efficiency of robot navigation combined with wrist arthroscopy in minimally invasive treatment of nondisplaced type Herbert D1 scaphoid fracture. A retrospective analysis was performed on 9 patients who underwent nondisplaced type Herbert D1 scaphoid fracture in Xuzhou Renci Hospital from December 2019 to January 2021. Before the operation and at the last follow-up, grip strength, pinching force, modified wrist Mayo score and visual analogue scale (VAS) of wrist pain were recorded and compared. The average follow-up time was 14.1 months (7.5-24.0 months). All the fractures achieved primary healing after an average of 13.3 weeks (10-18 weeks). The average flexion and dorsal extension activity of the injured wrist was 51.2°±9.4°, 68.0°±7.3°, and the radial and ulnar deviation was 19.3°±6.2°, 45.7°±7.8°, respectively. At the final follow-up, there were statistically significant differences in grip strength, pinch strength, wrist Mayo score and VAS when compared with those before the operation (all P<0.05). The results demonstrated that robot navigation combined with wrist arthroscopy for nondisplaced type Herbert D1 scaphoid fracture is effective and minimally invasive with a short recovery time and satisfactory healing rate.

Telomere and ATM Dynamics in CD4 T-Cell Depletion in Active and Virus-Suppressed HIV Infections.

CD4 T-cell depletion is a hallmark of HIV/AIDS, but the underlying mechanism is still unclear. We have recently shown that ataxia-telangiectasia-mutated (ATM) deficiency in CD4 T cells accelerates DNA damage, telomere erosion, and cell apoptosis in HIV-infected individuals on antiretroviral therapy (ART). Whether these alterations in ART-treated HIV subjects occur in vitro in HIV-infected CD4 T cells remains unknown. In this study, we employed a cellular model of HIV infection to characterize the mechanisms underlying CD4 T-cell destruction by analyzing the telomeric DNA damage response (DDR) and cellular apoptosis in highly permissive SupT1 cells, followed by the validation of our observations in primary CD4 T cells with active or drug-suppressed HIV infection. Specifically, we established an in vitro HIV T-cell culture system with viral replication and raltegravir (RAL; an integrase inhibitor) suppression, mimicking active and ART-controlled HIV infection in vivo We demonstrated that HIV-induced, telomeric DDR plays a pivotal role in triggering telomere erosion, premature T-cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways. This in vitro model provides a new tool to investigate HIV pathogenesis, and our results shed new light on the molecular mechanisms of telomeric DDR and CD4 T-cell homeostasis during HIV infection.IMPORTANCE The hallmark of HIV infection is a gradual depletion of CD4 T cells, with a progressive decline of host immunity. How CD4 T cells are depleted in individuals with active and virus-suppressed HIV infection remains unclear. In this study, we employed a cellular model of HIV infection to characterize the mechanisms underlying CD4 T-cell destruction by analyzing the chromosome end (telomere) DNA damage response (DDR) and cellular apoptosis in a T-cell line (highly permissive SupT1 cells), as well as in primary CD4 T cells with active or drug-suppressed HIV infection. We demonstrated that HIV-induced telomeric DDR plays a critical role in inducing telomere loss, premature cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways. This study sheds new light on the molecular mechanisms of telomeric DDR and its role in CD4 T-cell homeostasis during HIV infection.

Muscle wasting, a neglected complication associated with physical dysfunction in elderly patients with rheumatoid arthritis: a cross-sectional observational study.

Objective: Little is known about muscle wasting in elderly patients with rheumatoid arthritis (RA). We examined muscle characteristics and their clinical significance in this group.Method: Consecutive RA patients were recruited and clinical data were collected. Muscle mass and distribution were assessed using bioelectric impedance analysis. Myopenia was defined as an appendicular skeletal muscle mass index (ASMI) ≤ 7.0 kg/m2 (men) and ≤ 5.7 kg/m2 (women).Results: Among the 643 RA patients recruited, 165 (25.7%) were elderly patients (age ≥ 60 years) with a mean age of 65.1 ± 4.5 years. Compared with young patients (age < 60 years), elderly RA patients had significantly higher Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) (median 3.4 vs 3.2), Health Assessment Questionnaire Disability Index (HAQ-DI) (0.38 vs 0.13), and modified total Sharp score (mTSS) (16 vs 9), and a higher proportion of myopenia (54.5% vs 41.4%; all p < 0.01). Elderly RA patients with myopenia (n = 90, 14.0%) had significantly higher DAS28-CRP (3.6 vs 3.0), HAQ-DI (0.50 vs 0.12), and mTSS (21 vs 7) than young RA patients without myopenia (n = 280, 43.5%; all p < 0.0083). Multivariate logistic and linear regression analyses showed that myopenia, high HAQ-DI, active smoking, hypertension, diabetes, and coronary atherosclerotic heart disease were the main relevant characteristics of elderly RA patients. Age positively correlated with HAQ-DI, and ASMI negatively correlated with HAQ-DI (both p < 0.01). Further mediation analysis showed that ASMI partially mediated the association between age and HAQ-DI.Conclusion: Our data reveal that half of elderly RA patients manifest myopenia which aggravates physical dysfunction as a mediator of age. Myopenia, a neglected complication in elderly RA patients, should be recognized and further investigated.

Visible wide-angle view imaging system for the first plasma on the HL-2M tokamak.

The wide-angle view imaging system, in terms of a tangential view diagnostic with field of view (FOV) of 56.8° and a downward-looking diagnostic from the top of the machine with FOV of 94.7°, has been newly constructed for the first plasma of the HL-2M tokamak achieved in December 2020. Its mission in this stage is to monitor the plasma evolution during its startup, sustainment, and disruption in the visible spectral range as well as the plasma-wall interaction. For the latter ultrawide view diagnostic, nearly three-quarters of the divertor region and half the area of the inner wall are in the view range. Both the diagnostics are characterized by a similar optical structure, i.e., the light emission from the plasma is collected by a front-end lens and transferred through an imaging fiber bundle to the camera. This optical structure is suitable for application in the complex tokamak environment mainly because the fiber bundle is flexible. Photos of glow discharges are acquired prior to the first plasma for testing the FOVs in the vacuum vessel. The spatial resolution is ∼4mm for the tangential view diagnostic and ∼10mm for the downward-looking diagnostic. The temporal resolutions, ranging from 90 to 360 Hz by changing the region of interest or binning acquisition mode of the color camera, are applied to record the plasma evolutions and/or dust creation events during the first plasma campaign.

[Serological screening and analysis of clinical characteristics for celiac disease in susceptible population in Southern China].

Objective: To determine the seroprevalence of celiac disease in susceptible population, and to analyze the relationship between demographic characteristics, dietary habits, lifestyle and serological positivity so as to provide guidance for the prevention and treatment of celiac disease in Southern China. Methods: A total of 1 273 individuals who participated in Guangdong Province Health Screening Program in 2015, were selected as serologically positive subjects of celiac disease, including people with irritable bowel syndrome, colitis, diarrhea, anemia, low BMI, short stature, type 1 diabetes mellitus (T1DM), rheumatoid arthritis (RA), ankylosing spondylitis, psoriasis and bristol grade=6 or 7. All subjects were tested for serum IgA anti-tissue transglutaminase antibodies (TTGA), IgA antibodies against deamidated gliadin peptides(DGPA) and IgG against deamidated gliadin peptides (DGPG). Dietary habits, lifestyle and demographic characteristics were compared in subgroups. Results: The seroprevalence of celiac disease in susceptible population was 0.94% (95%CI 0.54%-1.64%) including 0.08% (1/1 273) for TTGA, 0.47% (6/1 273) for DGPA, and 0.39% (5/1 273) for DGPG. The seropositive rate was 3.6% (1/28) in patients with psoriasis, 2.1% (2/95) in the low BMI group, 1.9% (1/53) in T1DM group, 1.8% (3/169) in diarrhea group and 1.1% (5/463) in RA group. No significant difference was found in age, gender, high carbohydrate diet or lifestyle between the negative and the positive subjects. Conclusions: In Southern China, the seropositive rate of celiac disease is 0.94% in susceptible population, which prompts an urgent need of serological screening for early diagnosis.