Erratum - MMP-7 is upregulated by COX-2 and promotes proliferation and invasion of lung adenocarcinoma cells.

This corrects the article published in the European Journal of Histochemistry 2014;58:2262. doi: 10.4081/ejh.2014.2262.

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.

Removal of intraglandular calculi in Wharton's duct: clinical outcome and treatment algorithm.

The aim of this study was to propose a treatment strategy for intraglandular submandibular calculi based on calculus site. Seventy-three consecutive patients with impalpable intraglandular submandibular calculi were enrolled retrospectively. The calculi were classified as either post-hilar type, central type, or superficial type. Treatment approaches included transoral duct slitting (TDS), interventional basket retrieval (IBR), intraductal laser lithotripsy (ILL), and transcervical lithotomy (TCL). Complete calculus removal with gland preservation was achieved in 64 patients (87.7%). The success rate for post-hilar, central, and superficial calculi was 86.4% (51/59), 90.9% (10/11), and 100% (3/3), respectively. The treatment approach applied in patients with treatment success was TDS in 32 cases, IBR in 20, ILL in nine, and TCL in three. During follow-up (median 17.3 months), one patient experienced gland atrophy and three had ductal stenosis; the remaining 60 patients (93.8%, 60/64) had good clinical outcomes. In the eight failure cases operated by TDS, the deeply situated calculi could not be detached despite the parenchymal incision in five cases, while the procedure was ceased due to the patient's inability to cooperate in the other three cases. In the remaining failure case, the submandibular gland was sacrificed after calculus extraction via TCL. Application of the proposed treatment algorithm might help preserve gland function in patients with intraglandular submandibular calculi.

Association of healthy sleep patterns with risk of mortality and life expectancy at age of 30 years: a population-based cohort study.

BACKGROUND: The importance of sleep on cardiovascular health has been increasingly acknowledged. However, the effect of combined sleep behaviors on life expectancy remains understudied. AIM: To investigate the association between sleep patterns with total and cause-specific mortality and life expectancy, using a nationally representative sample of US adults. DESIGN: Population-based cohort study. METHODS: This cohort study included 172 321 adults aged 18 years or older in the National Health Interview Survey (2013-18) with linkage to the National Death Index records up to 31 December 2019. The life expectancy at the age of 30 years by the number of low-risk sleep scores was estimated using a flexible parametric survival model. RESULTS: During a median follow-up of 4.3 years, of the 172 321 adults (50.9% women; mean [SE] age, 46.98 [0.10] years), 8681 individuals died. The adjusted hazard ratios (95% confidence intervals [CI]) of participants with five vs. 0-1 low-risk sleep factors for all-cause, cardiovascular, and cancer mortality were 0.70 (0.63-0.77), 0.79 (0.67-0.93) and 0.81 (0.66-0.98), respectively. Nearly 8% (population attributable fraction 7.9%, 95% CI: 5.5-10.4) of mortality in this cohort could be attributed to suboptimal sleep patterns. When compared to those with 0-1 low-risk sleep factors, life expectancy at the age of 30 years for individuals with all five low-risk sleep factors was 4.7 (95% CI: 2.7-6.7) years greater for men and 2.4 (95% CI: 0.4-4.4) years greater for women. CONCLUSIONS: Our findings suggest that greater adherence to a low-risk sleep pattern may lead to significant gains in life expectancy among US adults.

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.

[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.

[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.

Recovery of gland function after endoscopy-assisted removal of impacted hilo-parenchymal stones in the Wharton's duct.

The aim of this study was to evaluate the gland function of patients following endoscopy-assisted removal of impacted hilo-parenchymal stones in the Wharton's duct. The study cohort comprised 115 patients who had undergone successful endoscopy-assisted lithotomy for hilo-parenchymal stones (mean diameter 7.7 mm). Gland function was evaluated at a mean 12 months after surgery using ultrasonography, sialography, and/or sialometry. Postoperative ultrasonography of 51 affected glands revealed a regular gland size in 58.8%, normal parenchyma density in 51.0%, and ductal ectasia in 80.4%. Postoperative sialograms of 109 affected glands were scored as type I (approximately normal) in 13 cases, type II (saccular ectasia of the hilo-parenchymal duct with/without stenosis, and no contrast retention) in 64, type III (saccular ectasia of the hilo-parenchymal duct with/without stenosis, and mild contrast retention) in 23, and type IV (poor shape of the main duct with evident contrast retention) in nine cases. The existence of ductal ectasia corresponded well to larger stone cases (P = 0.002). In the postoperative sialometry of 35 patients with unilateral stones, differences between the two sides were insignificant (P > 0.05). For patients with hilo-parenchymal submandibular gland stones, endoscopy-assisted surgery and extended postoperative follow-up help preserve the gland with good function.

Comparison of two transcutaneous approaches for the removal of impacted parotid stones.

The aim of this study was to comparatively evaluate the indications and treatment outcomes of two transcutaneous approaches for the removal of impacted parotid stones. Sixty-eight consecutive patients with impacted parotid stones underwent endoscopy-assisted lithotomy via a direct mini-incision or a peri-auricular flap. Clinical safety and outcomes were evaluated. Complete stone extraction was achieved in all patients. In the mini-incision group (52 patients), the stones were in the middle third of the main duct in 31 patients, at the hilum in 16, and in the intraglandular duct in five. In the flap group (16 patients), they were in the middle third of the main duct in one patient, at the hilum in seven, and in the intraglandular duct in eight. Salivary fistula occurred in five mini-incision group patients (9.6%) and four flap group patients (25%). The clinical outcome in the mini-incision group (47 patients, median 25 months of follow-up) was good in 28 patients, fair in 13, and poor in six (12.8%). The clinical outcome in the flap group (16 patients, median 84 months of follow-up) was good in nine patients, fair in five, and poor in two (12.5%). The direct mini-incision approach was found to be safe and effective for impacted stones in the middle third, hilum, and proximal third of the main duct, while the peri-auricular approach would be best reserved for deeper intraglandular stones.

[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.

Visual Acuity, Retinal Morphology, and Patients' Perceptions after Voretigene Neparovec-rzyl Therapy for RPE65-Associated Retinal Disease.

OBJECTIVE: To explore the effect of patients' age, baseline visual acuity (VA), and intraoperative foveal detachment on outcomes of subretinal voretigene neparvovec-rzyl (Luxturna) therapy and to assess patients' perceptions of the treatment effect. DESIGN: Multicenter, retrospective, consecutive case series, and cross-sectional prospective survey. PARTICIPANTS: All 41 consecutive patients treated with voretigene neparvovec-rzyl after Food and Drug Administration approval at 3 institutions between January 2018 and May 2020. METHODS: A retrospective chart review of operative reports, clinical notes, ancillary testing, and complications, comparing data at baseline and at 1, 2 to 3, 6 to 9, and 10 to 15 months after subretinal surgery was conducted. A survey was administered to adult patients and parents of pediatric patients. MAIN OUTCOME MEASURES: Changes in best-corrected VA and retinal morphology and in patients' perceptions. RESULTS: Seventy-seven eyes of 41 patients (16 adults and 25 pediatric patients; age range, 2-44 years; mean follow-up, 10 months [range, 1 week to 18.5 months]) were analyzed. There was no statistically significant vision change for the adults, whereas there was a trend of improvement for pediatric patients, which reached statistical significance for some time points. The baseline VA did not affect the posttherapy VA (P = 0.23). The central foveal thickness decreased mildly in both pediatric patients and adults, without significant differences between the populations. The fovea was detached by voretigene neparvovec-rzyl in 62 (81%) eyes. The inner segment-outer segment junction remained unchanged in 91% of 54 eyes with gradable OCT, with or without foveal detachment. Thirty-two (78%) patients were reached for the survey an average of 1.15 ± 0.50 years (range, 0.31 to 2.31) after the surgery in the first eye. Improvement in night, day, or color vision was reported by 23 (72%), 22 (69%), and 18 (56%) patients, respectively. CONCLUSIONS: This study is limited by the large variability in follow-up time. There were no persistent statistically significant vision changes. A decrease in foveal thickness was noted in most eyes, but the long-term significance of this remains to be determined.

[New agents-based induction chemotherapy followed by autologous stem cell transplantation and maintenance treatment strategy for multiple myeloma: a single center retrospective study of 300 cases].

Objective: To examine the survival and influential factors of an integrated approach of novel agents, autologous hematopoietic stem cell (auto-HSCT) , and maintenance therapy in patients with multiple myeloma (MM) patients from a single center over the past 15 years. Methods: In our center, 300 MM patients who received an integrated strategy of new agents, auto-HSCT, and maintenance therapy over 15 years were retrospectively and prospectively analyzed. Results: The complete remission rates (CR) and ≥very good partial remission rates (VGPR) following induction therapy, transplantation, and maintenance therapy were respectively 35.3% and 55.2% , 72.4% and 80.0% , 89.2% , and 93.4% . When compared to patients receiving double-drug induction, the ≥VGPR and ORR of patients receiving triple-drug induction were improved. No difference existed in CR, ≥VGPR, and ORR between the PAD (bortezomib + liposome doxorubicin+ dexamethasone) and RAD (lenalidomide + liposome doxorubicin + dexamethasone) regimens, but the benefits speed differed. The negative rate of flow minimal residual disease following induction, transplantation, and maintenance was 18.8% (54 cases) , 41.4% (109 cases) , and 58.7% (142 cases) , respectively. The median time to progress (TTP) was 78.7 months and the median overall survival (OS) was 109 months. The median TTP for RISS-Ⅰ-Ⅲ patients were 111.8 months, 77.4 months, and 30.6 months, and the median OS was 118.8 months, 91.4 months, and 48.5 months, respectively. At various points during treatment, the TTP and OS of patients obtaining CR and MRD negative were longer than those of patients who did not obtain CR and MRD negative. TTP was noticeably shorter in high-risk cytogenetic patients compared to standard-risk patients even when CR was acquired during induction. There was no difference in TTP between patients with high-risk cytogenetics and those with standard-risk cytogenetics if MRD negative was acquired during induction. According to a multivariate analysis, the R-ISS stage was a poor predictor of TTP and OS at various treatment intervals. Therapeutic effectiveness was a newly independent prognostic factor following treatment. Conclusion: A median survival of almost 10 years is possible for MM patients who receive an integrated strategy of induction regimens followed by auto-HSCT and maintenance therapy, which significantly improves prognosis. However, this approach did not significantly benefit high-risk cytogenetic MM patients.

[A comparative study of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of primary hyperaldosteronism on left side].

Objective: To compare the therapeutic effect of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of left-sided primary hyperaldosteronism. Methods: From January 2017 to July 2019, the clinical data of 70 patients with left-sided primary hyperaldosteronism (PHA) who underwent surgery in the First Hospital of Lanzhou University and five other hospitals in Gansu Province were retrospectively analyzed. There are 43 male and 27 female patients. Among them,28 patients were performed transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy and 42 patients were performed transperitoneal paracolic sulci approach laparoscopic adrenal tumorectomy. The general information and perioperative data of the two groups were compared. Results: All 70 cases of surgery were successfully completed. As compared with the paracolic sulci approach group, the operation time was significantly shorter in the transmesenteric approach group[(26.7±8.8)vs (38.9±7.1)min,P<0.001)], and the estimated blood loss was less in the transmesenteric approach group[45(30,50) vs 50(40,60)ml,P=0.042]. There was no statistically significant difference in the postoperative hospitalization days between the two groups[(4.4±1.0)vs(4.5±1.0)d, P=0.669)]. The electrolytes and aldosterone to renin ratio returned to a healthy level in the postoperative one month, and the blood pressure also returned to a healthy level in 53 (75.7%) patients. Conclusion: Transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy is safe and feasible, with a short operation time and relatively less estimated blood loss.

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.

Long Non-coding RNA GAS5 Regulates T Cell Functions via miR21-Mediated Signaling in People Living With HIV.

T cells are critical for the control of viral infections and T cell responses are regulated by a dynamic network of non-coding RNAs, including microRNAs (miR) and long non-coding RNAs (lncRNA). Here we show that an activation-induced decline of lncRNA growth arrest-specific transcript 5 (GAS5) activates DNA damage response (DDR), and regulates cellular functions and apoptosis in CD4 T cells derived from people living with HIV (PLHIV) via upregulation of miR-21. Notably, GAS5-miR21-mediated DDR and T cell dysfunction are observed in PLHIV on antiretroviral therapy (ART), who often exhibit immune activation due to low-grade inflammation despite robust virologic control. We found that GAS5 negatively regulates miR-21 expression, which in turn controls critical signaling pathways involved in DNA damage and cellular response. The sustained stimulation of T cells decreased GAS5, increased miR-21 and, as a result, caused dysfunction and apoptosis in CD4 T cells. Importantly, this inflammation-driven T cell over-activation and aberrant apoptosis in ART-controlled PLHIV and healthy subjects (HS) could be reversed by antagonizing the GAS5-miR-21 axis. Also, mutation of the miR-21 binding site on exon 4 of GAS5 gene to generate a GAS5 mutant abolished its ability to regulate miR-21 expression as well as T cell activation and apoptosis markers compared to the wild-type GAS5 transcript. Our data suggest that GAS5 regulates TCR-mediated activation and apoptosis in CD4 T cells during HIV infection through miR-21-mediated signaling. However, GAS5 effects on T cell exhaustion during HIV infection may be mediated by a mechanism beyond the GAS5-miR-21-mediated signaling. These results indicate that targeting the GAS5-miR-21 axis may improve activity and longevity of CD4 T cells in ART-treated PLHIV. This approach may also be useful for targeting other infectious or inflammatory diseases associated with T cell over-activation, exhaustion, and premature immune aging.

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.

[A prospective randomized controlled clinical study on the treatment of hypertrophic scar after burn by fractional carbon dioxide laser combined with autologous fat injection].

Objective: To explore the clinical effects of fractional carbon dioxide laser combined with autologous fat injection in the treatment of hypertrophic scar after burn. Methods: From April 2018 to April 2019, 12 patients with hypertrophic scar after burn who met the inclusion criteria were admitted to the Department of Plastic Surgery and Burns of Xuzhou Renci Hospital, and were included in this prospective randomized controlled clinical study. There were 7 males and 5 females with age of (32±11) years and scar area of (612±195) cm(2). One scar was selected from each patient and divided into two equal area scars, and they were divided into combined treatment group and laser alone group with 12 scars in each group according to the random number table. The scar in laser alone group was only treated with fractional carbon dioxide laser, while the scar in combined treatment group was injected with autologous granular fat and then treated with fractional carbon dioxide laser. Scars in the two groups were treated once every 2 months, totally 3 times. Before the first treatment and 6 months after the last treatment, the scars in the two groups were evaluated by modified Vancouver Scar Scale (mVSS), hematoxylin-eosin staining and color Doppler ultrasound. Six months after the last treatment, the curative effect of scars in the two groups was evaluated, and the effective number of scar treatment was calculated. The adverse reactions during the whole treatment were recorded. Data were statistically analyzed with independent sample t test, paired sample t test, and McNemar exact probability method test. Results: Six months after the last treatment, the mVSS score of scars in combined treatment group was (4.5±0.4) points, which was significantly lower than (7.8±0.6) points in laser alone group (t=10.000, P<0.01). Six months after the last treatment, the mVSS scores of scars in combined treatment group and laser alone group were significantly lower than those before the first treatment ((13.5±0.7) and (13.8±0.6) points, t=8.805, 9.010, P<0.01). The effective number of scar treatment in combined treatment group was significantly more than that in laser alone group (P<0.05). There was no scar aggravation, infection, or other adverse reactions during the treatment of scars in both groups. Before the first treatment, the scars in both groups had large collagen, disordered arrangement, proliferation of capillaries, infiltration of some inflammatory cells, and disappearance of skin appendages. Six months after the last treatment, the scar collagen in both groups was sparse and orderly arranged, and the vascular density was reduced. The improvement of scars in combined treatment group was more obvious than that of laser alone group. Six months after the last treatment, the scar thickness in combined treatment group was significantly smaller than that in laser alone group (t=2.657, P<0.05). Before the first treatment, the blood flow of scars in both groups was abundant; 6 months after the last treatment, the blood flow of scars in combined treatment group was significantly less than that in laser alone group. Conclusions: Fractional carbon dioxide laser combined with autologous fat injection in the treatment of hypertrophic scar after burn can significantly reduce the pain and itching symptoms of scar, and improve the thickness, texture, and congestion of scar. The combined treatment has synergistic effect and less adverse reactions, providing a more effective treatment for patients with hypertrophic scar.

Telomeric injury by KML001 in human T cells induces mitochondrial dysfunction through the p53-PGC-1α pathway.

Telomere erosion and mitochondrial dysfunction are prominent features of aging cells with progressive declines of cellular functions. Whether telomere injury induces mitochondrial dysfunction in human T lymphocytes, the major component of adaptive host immunity against infection and malignancy, remains unclear. We have recently shown that disruption of telomere integrity by KML001, a telomere-targeting drug, induces T cell senescence and apoptosis via the telomeric DNA damage response (DDR). In this study, we used KML001 to further investigate the role and mechanism of telomere injury in mitochondrial dysregulation in aging T cells. We demonstrate that targeting telomeres by KML001 induces mitochondrial dysfunction, as evidenced by increased mitochondrial swelling and decreased mitochondrial membrane potential, oxidative phosphorylation, mitochondrial DNA content, mitochondrial respiration, oxygen consumption, glycolysis, and ATP energy production. Mechanistically, we found that the KML001-induced telomeric DDR activated p53 signaling, which in turn repressed the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and nuclear respiratory factor 1 (NRF-1), leading to T cell mitochondrial dysfunction. These results, forging a direct link between telomeric and mitochondrial biology, shed new light on the human T cell aging network, and demonstrate that the p53-PGC-1α-NRF-1 axis contributes to mitochondrial dysfunction in the setting of telomeric DDR. This study suggests that targeting this axis may offer an alternative, novel approach to prevent telomere damage-mediated mitochondrial and T cell dysfunctions to combat a wide range of immune aging-associated human diseases.

Long non-coding RNA MNX1-AS1 promotes migration and invasion of esophageal squamous cell carcinoma by upregulating IGF2.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA MNX1-AS1 promotes migration and invasion of esophageal squamous cell carcinoma by upregulating IGF2, by D.-N. Zheng, C.-J. Zhang, G.-P. Sun, published in Eur Rev Med Pharmacol Sci 2019; 23 (14): 6179-6185-DOI: 10.26355/eurrev_201907_18431-PMID: 31364117" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18431.