Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease (COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathway is one of the proteolytic systems that significantly affect skeletal muscle structure and function. Intriguingly, both promoting and inhibiting autophagy have been observed to improve COPD skeletal muscle dysfunction, yet the mechanism is unclear. This paper first reviewed the effects of macroautophagy and mitophagy on the structure and function of skeletal muscle in COPD, and then explored the mechanism of autophagy mediating the dysfunction of skeletal muscle in COPD. The results showed that macroautophagy- and mitophagy-related proteins were significantly increased in COPD skeletal muscle. Promoting macroautophagy in COPD improves myogenesis and replication capacity of muscle satellite cells, while inhibiting macroautophagy in COPD myotubes increases their diameters. Mitophagy helps to maintain mitochondrial homeostasis by removing impaired mitochondria in COPD. Autophagy is a promising target for improving COPD skeletal muscle dysfunction, and further research should be conducted to elucidate the specific mechanisms by which autophagy mediates COPD skeletal muscle dysfunction, with the aim of enhancing our understanding in this field.
Pulmonary Disease, Chronic Obstructive/physiopathology* ; Autophagy/physiology* ; Humans ; Muscle, Skeletal/pathology* ; Mitophagy ; Animals ; Mitochondria/metabolism* ; Lysosomes

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Supratentorial cerebral hemorrhage complicated by brain herniation has high disability and mortality rates,and surgical treatment can improve cerebral perfusion,brain tissue metabolism,and hematoma clearance and promote neurological function recov-ery,with the main surgical procedures of craniotomy,endoscopic surgery,and stereotactic surgery.Different treatment methods have a certain value in the treatment of patients with supratentorial cerebral hemorrhage and brain herniation,and in recent years,an increas-ing number of studies have focused on the comparison of the impact of different treatment methods on prognosis.This article reviews re-lated research advances and compares thedifferent treatment methods for patients with supratentorial cerebral hemorrhage and brain herniation,in order to provide a reference for clinical diagnosis and treatment.

Objective To systematically assess the spatiotemporal distribution,risk factors,and future trends of chronic obstructive pulmonary disease(COPD)among individuals under 50 years of age globally from 1990 to 2021 based on Global Burden of Disease(GBD)data in order to provide support for the formulation of prevention and control strategies of the disease.Methods The GBD data from 1990 to 2021 were analyzed for the incidence,mortality,disability-adjusted life years(DALYs),and estimated annual percentage change(EAPC)of COPD in<50-year-old individuals across 204 countries and regions.The data were stratified by age,sex,region,country,and sociodemographic index(SDI).The COPD trends until 2035 were predicted.Results In 2021,the global incidence of early-onset COPD was estimated at 2.5 million cases(95%uncertainty interval:2.09～2.96 million),representing a 50.55%increase compared to 1990.Significant regional heterogeneity was observed,with low SDI regions experiencing a 134.08%increase,whereas high SDI regions exhibited a rise-then-fall trend.Risk factor analysis identified environmental and occupational exposures(air pollution,ambient ozone pollution,household air pollution from solid fuels,etc.)and smoking as the primary etiological factors.Notably,household solid fuel exposure accounted for 50.90%of COPD-related deaths in low SDI regions,compared to only 0.03%in high SDI regions.Projections indicated that by 2035,the global burden of early-onset COPD will increase to 2.59 million cases.Conclusion The global disease burden of COPD among people under 50 years increased significantly from 1990 to 2021,with pronounced disparities across regions and socioeconomic levels.COPD deaths in low-SDI regions are strongly associated with solid fuel exposure and particulate matter pollution,and these regions are expected to remain the main drivers of global COPD incidence growth through 2035.

Background and objective Transcription factor(TF)can bind specific sequences that either promotes or represses the transcription of target genes,and exerts important effects on tumorigenesis,migration,invasion.Staphylococcal nuclease-containing structural domain 1(SND1),which is a transcriptional co-activator,is considered as a promising target for tumor therapy.However,its role in lung adenocarcinoma(LUAD)remains unclear.This study aims to explore the role of SND1 in LUAD.Methods Data from The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),Clinical Pro-teomic Tumor Analysis Consortium(CPTAC),and Human Protein Atlas(HPA)database was obtained to explore the associa-tion between SND1 and the prognosis,as well as the immune cell infiltration,and subcellular localization in LUAD tissues.Furthermore,the functional role of SND1 in LUAD was verified in vitro.EdU assay,CCK-8 assay,flow cytometry,scratch assay,Transwell assay and Western blot were performed.Results SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients.In addition,SND1 was predominantly present in the cytoplasm of LUAD cells.Enrichment analysis showed that SND1 was closely associated with the cell cycle,as well as DNA replication,and chro-mosome segregation.Immune infiltration analysis showed that SND1 was closely associated with various immune cell popula-tions,including T cells,B cells,cytotoxic cells and dendritic cells.In vitro studies demonstrated that silencing of SND1 inhib-ited cell proliferation,invasion and migration of LUAD cells.Besides,cell cycle was blocked at G,phase by down-regulating SND1.Conclusion SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.

Humans ; Transcranial Magnetic Stimulation ; Pain Management ; Psychotic Disorders/therapy* ; Depressive Disorder, Major ; Treatment Outcome ; Transcranial Direct Current Stimulation

Objective:To explore an early mobilization plan for oral cancer patients after free flap reconstruction and evaluate the application effect of the plan.Methods:This study was a prospective randomized controlled trial. A total of 173 patients undergoing free flap reconstruction surgery from December 2018 to December 2021 in the second ward of Peking University School and Hospital of Stomatology were selected. The patients were randomly divided into the control group (87 cases) and the intervention group (86 cases) by cluster randomized grouping. The control group received the routine nursing plan, that was, head immobilization for 4 days after surgery, and patients performed sat up and off-bed activity on the 5th day. The intervention group received the early mobilization plan, that was, patients sat up on the 2nd day after surgery and performed off-bed activity on the 3rd day. The incidence of vascular compromise, postoperative complications, sleep time in the first 5 days after surgery, catheter removal time, hospitalization duration and expenses were compared between the two groups.Results:The incidence of postoperative pulmonary infection, the daily sleep time in the first 5 days after surgery, the time for removing nasogastric tube, trachea cannula, and urinary catheter were 7.0%(6/86), (5.0 ± 1.0) h/d, (11.8 ± 7.3) d, (6.1 ± 3.2) d, (3.6 ± 0.6) d in the intervention group, and 13.8%(12/87), (4.4 ± 1.3) h/d, (14.2 ± 5.8) d, (7.3 ± 1.7) d, (4.0 ± 0.9) d in the control group, all differences were statistically significant ( χ2 = 3.89, t values were -3.57 - -2.44, all P<0.05). There was no significant difference in the incidence of rascular compromise, hospitalization duration and expenses between the two groups (all P>0.05). Conclusions:For patients undergoing free tissue flap reconstruction, it is safe to sit up on the 2nd day and get out of bed on the 3rd day, which can reduce the incidence of pulmonary infection, improve patient sleep, and shorten the indwelling time of nasogastric tube, trachea cannula and urinary catheter.

Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.

OBJECTIVE To explore the effects of Citrus medica before and after being steamed on blood metabolism and dryness indexes in rats. METHODS Twenty-four SD rats were randomly divided into blank group， C. medica group （2.4 g/kg）， processed C. medica group （2.4 g/kg）， Citrus aurantium group （positive control， 1.2 g/kg）， with 6 rats in each group. After 5 weeks of continuous administration， the body weight， food intake， water intake and urine volume were observed dynamically. The content of aquaporin 3 （AQP3） in serum was detected. The metabolic profile of rat serum samples was analyzed by liquid chromatography-mass spectrometry. Principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to screen differential metabolites， and screened differential metabolites were mapped to the KEGG database for pathway analysis. RESULTS The body weight of rats in each group increased slowly； the food intake and water intake of processed C. medica group tended to be higher than those in C. medica group and C. aurantium group， but there was no significant difference among those groups （P＞0.05）. On the 21st day of administration， compared with C. aurantium group， the urine volume of processed C. medica group was significantly increased （P＜0.05）， the serum AQP3 content of processed C. medica group was significantly decreased （P＜0.05）， and were close to those of blank group. According to the metabonomic study， C. medica mainly affected the lipids metabolism， and processed C. medica mainly affected the amino acid metabolism. The differential metabolites pathway between C. medica and processed C. medica involved the metabolism of cysteine and methionine， metabolism of glycine， serine and threonine， and metabolism of taurine and hypotaurine. CONCLUSIONS Processed C. medica might relieve the dryness of C. medica by affecting adenosine phosphate-protein kinase A. The content of AQP3 in serum can be used as the 52 evaluation index for the dryness of C. medica before and after processing. The effects of C. medica and processed C. medica on endogenous metabolites in rat serum are quite different，especially in the aspect of lipid metabolism.

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.
Aggrecans/metabolism* ; Animals ; Cartilage, Articular/metabolism* ; Chondrocytes/pathology* ; Cytoskeletal Proteins/metabolism* ; Mice ; Muscle Proteins/metabolism* ; Osteoarthritis/pathology* ; Temporomandibular Joint/pathology*