OBJECTIVE:A great deal of evidence indicates that regular exercise can improve the health status of elderly individuals,including reducing overall and abdominal fat levels,increasing muscle mass and bone mineral density of the limbs,thereby preventing or delaying the onset of sarcopenia and its comorbidities.This study aims to determine the most reliable type,duration,and intensity of exercise interventions through meta-analysis to prevent,delay,and alleviate sarcopenia and its comorbidities in elderly individuals.METHODS:Randomized controlled trials examining the effects of exercise interventions on elderly individuals with sarcopenia and its comorbidities were searched in the PubMed,Embase,Web of Science,Cochrane Library,CNKI,and WanFang databases.The Cochrane Risk of Bias Tool was used to assess the quality of the included studies,and RevMan 5.3 software was employed for meta-analysis.Subgroup analyses were conducted to explore the effects of different exercise intervention protocols on various outcome measures.In addition,Stata 16.0 software was used to perform sensitivity analysis to assess the stability of the results,and funnel plots and Egger's test were employed to evaluate publication bias,ensuring the comprehensiveness and reliability of the results.RESULTS:(1)Sixteen studies involving 861 patients with sarcopenia and its comorbidities were included.(2)The meta-analysis results indicated that,compared with the control group,exercise significantly improved grip strength,knee muscle strength,appendicular skeletal muscle mass,skeletal muscle index,Timed Up and Go test results,gait speed,and insulin-like growth factor 1 levels(P＜0.05).However,the effect of exercise intervention on the sit-to-stand test was not significantly improved(P＞0.05).(3)Based on the results of subgroup analysis,it is recommended that elderly patients with sarcopenia and its comorbidities engage in exercise at least three times per week,with each session lasting no more than 30 minutes or exceeding 45 minutes,for at least 12 weeks.The exercise protocol should be flexibly adjusted according to the patient's health status and individual needs.CONCLUSION:Exercise interventions significantly improve muscle mass,muscle strength,physical function,and insulin-like growth factor 1 levels in elderly individuals with sarcopenia and its comorbidities,thereby enhancing their quality of life.However,further research is needed to validate these findings and optimize specific intervention protocols.

OBJECTIVE:A great deal of evidence indicates that regular exercise can improve the health status of elderly individuals,including reducing overall and abdominal fat levels,increasing muscle mass and bone mineral density of the limbs,thereby preventing or delaying the onset of sarcopenia and its comorbidities.This study aims to determine the most reliable type,duration,and intensity of exercise interventions through meta-analysis to prevent,delay,and alleviate sarcopenia and its comorbidities in elderly individuals.METHODS:Randomized controlled trials examining the effects of exercise interventions on elderly individuals with sarcopenia and its comorbidities were searched in the PubMed,Embase,Web of Science,Cochrane Library,CNKI,and WanFang databases.The Cochrane Risk of Bias Tool was used to assess the quality of the included studies,and RevMan 5.3 software was employed for meta-analysis.Subgroup analyses were conducted to explore the effects of different exercise intervention protocols on various outcome measures.In addition,Stata 16.0 software was used to perform sensitivity analysis to assess the stability of the results,and funnel plots and Egger's test were employed to evaluate publication bias,ensuring the comprehensiveness and reliability of the results.RESULTS:(1)Sixteen studies involving 861 patients with sarcopenia and its comorbidities were included.(2)The meta-analysis results indicated that,compared with the control group,exercise significantly improved grip strength,knee muscle strength,appendicular skeletal muscle mass,skeletal muscle index,Timed Up and Go test results,gait speed,and insulin-like growth factor 1 levels(P＜0.05).However,the effect of exercise intervention on the sit-to-stand test was not significantly improved(P＞0.05).(3)Based on the results of subgroup analysis,it is recommended that elderly patients with sarcopenia and its comorbidities engage in exercise at least three times per week,with each session lasting no more than 30 minutes or exceeding 45 minutes,for at least 12 weeks.The exercise protocol should be flexibly adjusted according to the patient's health status and individual needs.CONCLUSION:Exercise interventions significantly improve muscle mass,muscle strength,physical function,and insulin-like growth factor 1 levels in elderly individuals with sarcopenia and its comorbidities,thereby enhancing their quality of life.However,further research is needed to validate these findings and optimize specific intervention protocols.

Objective To analyze the risk factors for chronic mountain sickness(CMS)in young male migrants living in high-altitude areas and to construct a diagnostic model and evaluate its diagnostic efficacy.Methods From June 10 to December 29,2023,a cross-sectional study was conducted on young male migrants subjected with convenience sampling who had been living in high-altitude areas(4 500～5 000 m)for 6 months or longer.Their demographic data were collected and blood samples were collected for laboratory test.According to the Qinghai Score for Chronic Mountain Sickness,they were divided into CMS group and non-CMS group.Then the participants were randomly divided into a training set and a test set in a ratio of 8∶2.Independent risk factors for CMS occurrence were screened out,through random forest variable importance ranking,univariate and multivariable logistic regression analysis,and a diagnostic model was constructed based on these factors.Receiver operating characteristic(ROC)curve analysis,calibration curve analysis,clinical decision curve analysis,and influence curve analysis were used to comprehensively evaluate the diagnostic performance of the model.Results According to the inclusion and exclusion criteria,308 out of 376 participants were finally subjected,and 17.53%of them were diagnosed with CMS.The major clinical symptoms of the CMS patients were dyspnea or palpitations(79.63%)and sleep disorders(85.19%).Further analysis revealed that creatine kinase-MB/creatine kinase(CK-MB/CK,OR=2.17,95%CI:1.43～3.28),high-altitude residence time(OR=2.44,95%CI:1.08～5.54),and body mass index(BMI,OR=1.62,95%CI:1.05～2.50)were 3 major independent risk factors for CMS.The area under the curve(AUC)value of the CMS diagnostic model in the training set and test set was 0.821(95%CI:0.756～0.886)and 0.821(95%CI:0.700～0.944),the specificity was 66.30%and 73.90%,the sensitivity was 89.50%and 81.20%,respectively,indicating good discrimination ability.Hosmer-Lemeshow goodness-of-fit test showed consistency between predicted results and actual observations(χ2=10.029,P=0.263;χ2=4.477,P=0.812).Clinical decision curve analysis demonstrated that within the threshold probability range from 0.1 to 0.7,the net benefit of the model exceeded both full intervention and no intervention strategies.The influence curve analysis showed high consistency between the model predictions and actual incidence when the threshold probability exceeded 0.4.These two analyses together confirmed the clinical application value of the model.Conclusion CK-MB/CK,high-altitude residence time and BMI are independent risk factors for CMS,and their diagnostic model helps identify potential individuals at risk for CMS.Early intervention can prevent the harm of CMS to the health of young men migrating to high-altitude areas.

Objective To determine the effects of hypoxia pre-treatment combined with radiation damage on the hematopoietic cells in the bone marrow of mice.Methods A total of 165 male C57BL/6 mice(10～12 weeks old,weighing 20～25 g)were randomly divided into 7 groups:normal control(Control,n=33),6 Gy irradiation(6-Gy,n=43),7 d hypoxia-6 Gy irradiation(Hy-7 d+6 Gy,n=43),7 Gy irradiation(7 Gy,n=12),7 d hypoxia-7 Gy irradiation(Hy-7 d+7 Gy,n=12),7 Gy continuous hypoxia treatment(Hy-7 d+7 Gy+Hy,n=12),and 6 Gy continuous hypoxia treatment(Hy-7 d+6 Gy+Hy,n=10).The mice of the hypoxia treatment groups were given 7-day hypoxic pretreatment(12%oxygen)in a normobaric hypoxic chamber,while those of the other groups were housed in normoxic condition.After pretreatment,the mice of the irradiation groups were exposed to a single 6 or 7 Gy of whole-body 60Co γ-irradiation in normoxia.The mice of the hypoxia and irradiation groups were kept in hypoxic condition in 24 h post-irradiation followed by being resumed to normoxia,while those of the continuous hypoxia treatment groups were remained in hypoxia.After bone marrow cell suspensions were prepared from the Control,6 Gy,and Hy-7 d+6 Gy groups,bone marrow nucleated cells(BMNCs)were counted via automated cell counter.HE staining was employed to observe pathologic changes in medullary cavity,and flow cytometry was used to assess Lin-Sca1?c-Kit?(LSK)hematopoietic stem/progenitor cells,myeloid progenitors(MPs),and mature T/B/myeloid cells.The mice of the 7 Gy,Hy-7 d+7 Gy,and Hy-7 d+7 Gy+Hy groups were monitored for 30-day survival after hypoxic pretreatment.The dynamic changes in the counts of red blood cells(RBC),white blood cells(WBC)and platelets(PLT),and hemoglobin(HGB)level were observed in the 6 Gy,Hy-7 d+6 Gy,and Hy-7 d+6 Gy+Hy groups with aid of a fully automatic blood analyzer.Single-cell RNA sequencing was performed on bone marrow cell suspension derived from the mice euthanized in 17 d after irradiation from the Control,6 Gy,and Hy-7 d+6 Gy groups.Results ①Compared to the Control group,the 6 Gy group showed significantly reduced BMNCs(P<0.01),dilated bone marrow sinusoids,and erythrocyte extravasation.The Hy-7 d+6 Gy group exhibited higher cellular density and attenuated BMNC loss than the 6 Gy group(P<0.01).②Flow cytometry revealed less LSK,MP,and mature T/B/myeloid cells in the 6 Gy group than the Control group(P<0.05),and the reduced counts of LSK and MP were mitigated in the Hy-7 d+6 Gy group(P<0.01).③The Hy-7 d+7 Gy group demonstrated improved 30-day survival than the 7 Gy group(P<0.01),while continuous hypoxia(Hy-7 d+7 Gy+Hy)failed to enhance the survival.No statistical difference was seen in the survival rate between the 2 groups(P=0.12),though the Hy-7 d+7 Gy group showing higher survival rate.④Routine blood test revealed that the Hy-7 d+6 Gy group showed faster WBC recovery(vs the 6 Gy and Hy-7 d+6 Gy+Hy groups,P<0.05),higher pre-irradiation RBC/HGB levels,and accelerated PLT restoration(P<0.05).⑤Single-cell RNA sequencing indicated that hypoxia pretreatment suppressed the numbers of long-term hematopoietic stem cells/short-term hematopoietic stem cells(LT-HSC/ST-HSC)depletion in the Hy-7 d+6 Gy group when compared with the 6 Gy group,which was consistent with the results of flow cytometry.Pseudotime trajectory aligned the Hy-7 d+6 Gy group,as the Control group,showed enriched undifferentiated LSKs.Differential gene analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed that oxidative phosphorylation pathway was strongly activated in the 6 Gy group,while the Hy-7 d+6 Gy group had enriched in chromatin remodeling and mRNA surveillance pathways.Conclusion Hypoxic preconditioning alleviates radiation-induced bone marrow injury,and post-irradiation normoxia restoration promotes hematopoietic recovery in acute radiation-exposed mice.

China is currently in an accelerated stage of population aging, and brain diseases pose a significant threat to the health of the elderly. " Preventing brain aging and maintaining brain health" has become a high-level goal of healthy aging. During the process of aging, the physiological and psychological states of elderly people change, making them prone to nervousness and exhaustion, which can disturb the brain spirit, damage the brain collaterals, and severely endanger brain health. Starting from the holistic view of cultivating both body and spirit in traditional Chinese medicine, based on the physical and mental characteristics of the elderly, this paper applies the concept and method of " relaxation and tranquility" in the protection of elderly brain health, focusing on maintaining relaxation and tranquility in both physical and mental aspects. Specific measures include emphasizing subjective consciousness, relaxing the heart and calming down; utilizing the daoyin method, relaxing the body and calming down, combining relaxation and tranquility, cultivating both body and spirit to prevent diseases and protect the brain, which enables the elderly to have a healthy mind and body, a sense of happiness and fulfillment, and to age gracefully. Simultaneously, advocating for tranquility is also called " respect" for relaxation, following nature to understand constant changes, and improving one′s ability to think positively in old age, in order to expand ideas for the protection of elderly brain health.

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.