BACKGROUND:Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass,strength,and/or physical function.Currently,effective treatments for sarcopenia remain limited.A new therapeutic approach to improve symptoms and prognosis of sarcopenia patients clinically was important.OBJECTIVE:To explore the effects of canine adipose-derived mesenchymal stem cells and their exosomes on a dexamethasone-induced sarcopenia in mice.METHODS:Mesenchymal stem cells were isolated and cultured from canine adipose tissue,and identified and functionally evaluated through flow cytometry and differentiation assays for osteogenesis,adipogenesis,and chondrogenesis.Subsequently,exosomes from adipose-derived mesenchymal stem cells were extracted and characterized using transmission electron microscopy,western blot assay,and nanocoulter tracking analysis.In vitro,the effects of canine adipose-derived mesenchymal stem cells and their exosomes on myotube growth and the expression of muscle atrophy-related genes were investigated using dexamethasone-induced C2C12 myotube atrophy and aging C2C12 models.In vivo,a dexamethasone-induced mouse sarcopenia model was established and received intraperitoneal or intravenous injection of canine adipose-derived mesenchymal stem cells.Therapeutic efficacy was assessed through mouse rotarod performance,histopathological analysis,and muscle atrophy-related genes testing.RESULTS AND CONCLUSION:(1)The isolated canine adipose-derived mesenchymal stem cells highly expressed CD73,CD90,and CD105,and lowly expressed MHC-Ⅱ,CD14,CD19,CD34,and CD45,and successfully differentiated into osteoblasts,adipocytes,and chondrocytes in vitro.(2)The adipose-derived mesenchymal stem cells-derived exosomes met the identification criteria in terms of particle size,electron microscopy morphology,and positive expression of specific markers.(3)Compared to the dexamethasone-induced C2C12 atrophy group,treatment with adipose-derived mesenchymal stem cells and their exosomes promoted the recovery and growth of myotubes,inhibited the expression of muscle atrophy-related genes MuRF1 and Atrogin-1.(4)Compared to the aging C2C12 group,adipose-derived mesenchymal stem cells and their exosomes significantly enhanced the recovery and growth of aged muscle tubes in aging cells.(5)Compared to the control group,the rotarod time in dexamethasone-induced sarcopenia model mice was significantly decreased(P＜0.01).After 7 days(P＜0.01,P＜0.01)and 10 days(P＜0.01,P＜0.05)of adipose-derived mesenchymal stem cells treatment via intraperitoneal and intravenous injection,rotarod time was significantly increased,respectively.After 14 days,all treatment groups showed longer rotarod times than the model group,although with no significant differences between them.(6)Compared to the control group,the cross-sectional area of anterior tibial muscle in the model group was significantly reduced(P＜0.01),and it was significantly increased after intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells(P＜0.05,P＜0.01).(7)Compared to the model group,intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells significantly inhibited the mRNA expression of MuRF1 and Atrogin-1 genes(P＜0.01,P＜0.01,P＜0.01,P＜0.01).The results indicated that adipose-derived mesenchymal stem cells and their exosomes promoted recovery and growth of atrophic myotube cells by inhibiting the expression of muscle atrophy-related genes,and both intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells provided good therapeutic effects on sarcopenia in mice.

BACKGROUND:Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass,strength,and/or physical function.Currently,effective treatments for sarcopenia remain limited.A new therapeutic approach to improve symptoms and prognosis of sarcopenia patients clinically was important.OBJECTIVE:To explore the effects of canine adipose-derived mesenchymal stem cells and their exosomes on a dexamethasone-induced sarcopenia in mice.METHODS:Mesenchymal stem cells were isolated and cultured from canine adipose tissue,and identified and functionally evaluated through flow cytometry and differentiation assays for osteogenesis,adipogenesis,and chondrogenesis.Subsequently,exosomes from adipose-derived mesenchymal stem cells were extracted and characterized using transmission electron microscopy,western blot assay,and nanocoulter tracking analysis.In vitro,the effects of canine adipose-derived mesenchymal stem cells and their exosomes on myotube growth and the expression of muscle atrophy-related genes were investigated using dexamethasone-induced C2C12 myotube atrophy and aging C2C12 models.In vivo,a dexamethasone-induced mouse sarcopenia model was established and received intraperitoneal or intravenous injection of canine adipose-derived mesenchymal stem cells.Therapeutic efficacy was assessed through mouse rotarod performance,histopathological analysis,and muscle atrophy-related genes testing.RESULTS AND CONCLUSION:(1)The isolated canine adipose-derived mesenchymal stem cells highly expressed CD73,CD90,and CD105,and lowly expressed MHC-Ⅱ,CD14,CD19,CD34,and CD45,and successfully differentiated into osteoblasts,adipocytes,and chondrocytes in vitro.(2)The adipose-derived mesenchymal stem cells-derived exosomes met the identification criteria in terms of particle size,electron microscopy morphology,and positive expression of specific markers.(3)Compared to the dexamethasone-induced C2C12 atrophy group,treatment with adipose-derived mesenchymal stem cells and their exosomes promoted the recovery and growth of myotubes,inhibited the expression of muscle atrophy-related genes MuRF1 and Atrogin-1.(4)Compared to the aging C2C12 group,adipose-derived mesenchymal stem cells and their exosomes significantly enhanced the recovery and growth of aged muscle tubes in aging cells.(5)Compared to the control group,the rotarod time in dexamethasone-induced sarcopenia model mice was significantly decreased(P＜0.01).After 7 days(P＜0.01,P＜0.01)and 10 days(P＜0.01,P＜0.05)of adipose-derived mesenchymal stem cells treatment via intraperitoneal and intravenous injection,rotarod time was significantly increased,respectively.After 14 days,all treatment groups showed longer rotarod times than the model group,although with no significant differences between them.(6)Compared to the control group,the cross-sectional area of anterior tibial muscle in the model group was significantly reduced(P＜0.01),and it was significantly increased after intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells(P＜0.05,P＜0.01).(7)Compared to the model group,intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells significantly inhibited the mRNA expression of MuRF1 and Atrogin-1 genes(P＜0.01,P＜0.01,P＜0.01,P＜0.01).The results indicated that adipose-derived mesenchymal stem cells and their exosomes promoted recovery and growth of atrophic myotube cells by inhibiting the expression of muscle atrophy-related genes,and both intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells provided good therapeutic effects on sarcopenia in mice.

BACKGROUND: The mechanisms distinguishing metabolically healthy from unhealthy phenotypes within the same BMI categories remain unclear. This study aimed to investigate the associations between regional fat distribution and metabolically unhealthy phenotypes in Chinese adults across different BMI categories. METHODS: This cross-sectional study involving 11833 Chinese adults aged 20 years and older. Covariance analysis, adjusted for age, compared the percentage of regional fat (trunk, leg, or arm fat divided by whole-body fat) between metabolically healthy and unhealthy participants. Trends in regional fat percentage with the number of metabolic abnormalities were assessed by the Jonckheere-Terpstra test. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression models. All analyses were performed separately by sex. RESULTS: In non-obese individuals, metabolically unhealthy participants exhibited higher percent trunk fat and lower percent leg fat compared to healthy participants. Additionally, percent trunk fat increased and percent leg fat decreased with the number of metabolic abnormalities. After adjustment for demographic and lifestyle factors, as well as BMI, higher percent trunk fat was associated with increased odds of being metabolically unhealthy [highest vs. lowest quartile: ORs (95%CI) of 1.64 (1.35, 2.00) for men and 2.00 (1.63, 2.46) for women]. Conversely, compared with the lowest quartile, the ORs (95%CI) of metabolically unhealthy phenotype in the highest quartile for percent arm and leg fat were 0.64 (0.53, 0.78) and 0.60 (0.49, 0.74) for men, and 0.72 (0.56, 0.93) and 0.46 (0.36, 0.59) for women, respectively. Significant interactions between BMI and percentage of trunk and leg fat were observed in both sexes, with stronger associations found in individuals with normal weight and overweight. CONCLUSIONS Trunk fat is associated with a higher risk of metabolically unhealthy phenotype, while leg and arm fat are protective factors. Regional fat distribution assessments are crucial for identifying metabolically unhealthy phenotypes, particularly in non-obese individuals.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adipose Tissue ; Body Fat Distribution ; Body Mass Index ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Phenotype

Establishing a one-stop diagnosis and treatment mode centered on patients and linked by diseases is of great significance for optimizing the medical process and improving the medical experience. In March 2024, a tertiary hospital integrated pediatric outpatient and emergency resources, established a pediatric diagnosis and treatment island through reasonable department settings, strengthened talent team construction, optimized diagnosis and treatment processes, and established supporting guarantee mechanisms. It was officially put into use in June of the same year, providing one-stop diagnosis and treatment services for children and achieving the goal of " not leaving the island for minor illnesses and not leaving the hospital for major illnesses". Before the operation of island (January May 2024), the complaint rate and waiting time for pediatric outpatient and emergency department were 39 cases per 100 000 patients and 15 to 30 minutes, respectively; After operation (June August 2024), the complaint rate and waiting time decreased to 17 cases per 100 000 people and 10 to 20 minutes respectively; The average monthly comprehensive income of outpatient and emergency departments increased by 33%. The pediatric diagnosis and treatment island mode could assist in the sustainable high-quality development of pediatrics in hospital, and provide references for optimizing outpatient and emergency department management in other tertiary public hospitals. In the future, we should further enrich the service content of the island and strengthen information technology construction.

Establishing a one-stop diagnosis and treatment mode centered on patients and linked by diseases is of great significance for optimizing the medical process and improving the medical experience. In March 2024, a tertiary hospital integrated pediatric outpatient and emergency resources, established a pediatric diagnosis and treatment island through reasonable department settings, strengthened talent team construction, optimized diagnosis and treatment processes, and established supporting guarantee mechanisms. It was officially put into use in June of the same year, providing one-stop diagnosis and treatment services for children and achieving the goal of " not leaving the island for minor illnesses and not leaving the hospital for major illnesses". Before the operation of island (January May 2024), the complaint rate and waiting time for pediatric outpatient and emergency department were 39 cases per 100 000 patients and 15 to 30 minutes, respectively; After operation (June August 2024), the complaint rate and waiting time decreased to 17 cases per 100 000 people and 10 to 20 minutes respectively; The average monthly comprehensive income of outpatient and emergency departments increased by 33%. The pediatric diagnosis and treatment island mode could assist in the sustainable high-quality development of pediatrics in hospital, and provide references for optimizing outpatient and emergency department management in other tertiary public hospitals. In the future, we should further enrich the service content of the island and strengthen information technology construction.

The surgical treatment of colorectal cancer will be more and more accurate and minimally invasive under the guidance of precision medicine. At the same time, it will derive and evolve non-surgical paths, such as immune checkpoint inhibitors and immune targeted therapy for microsatellite instability high/mismatch repair deficient colorectal cancer, and wait and watch path after neoadjuvant treatment for low advanced rectal cancer. Laparoscopic minimally invasive surgery for colorectal cancer will be gradually iterated by robots, which is the only way to intelligent surgery.

The surgical treatment of colorectal cancer will be more and more accurate and minimally invasive under the guidance of precision medicine. At the same time, it will derive and evolve non-surgical paths, such as immune checkpoint inhibitors and immune targeted therapy for microsatellite instability high/mismatch repair deficient colorectal cancer, and wait and watch path after neoadjuvant treatment for low advanced rectal cancer. Laparoscopic minimally invasive surgery for colorectal cancer will be gradually iterated by robots, which is the only way to intelligent surgery.

Objective To study the influence of long term simulated weightlessness on occurrence of laryngopharyngeal reflux(LPR)in healthy volunteers by detection of pepsin in saliva.Methods During a 90-day head-down tilt bed rest(HDTBR)experiment,11 volunteers(4 from the control group and 7 from the countermeasure group)were recruited in the study in the following seven sessions:before bed rest session(Pre),during bed rest sessions for 3 days(BR3),31 days(BR31),61 days(BR61),85 days(BR85)and post bed rest sessions for 7 days(R7)and 25 days(R25).During each testing session,saliva samples were collected for two consecutive days both in the morning and at night before sleeping.Then pepsin in the saliva was measured by enzyme-linked immunosorbent assay.Scale of otorhinolaryngological symptoms for the duration of"Pre-,During-and Post-"were retrospectively performed.Results Among 288 saliva samples of 11 volunteers,17 saliva samples of 8 volunteers were positive for pepsin.The incidence of LPR was 9.1%(1/11)in the Pre session,and it increased to 36.4%in the BR31 session which was higher than the following consequential sessions(0%in BR31,27.3%in BR61 and 27.3%in BR85).Intriguingly,it rose again to 45.5%in R7 session and decreased to 9.1%until in R25 session.There was no significant difference between the control group and the countermeasure group.Total scores for the scale of otorhinolaryngological symptoms showed that a slight elevation tendency emerged during HDTBR session,compared with the pre-HDTBR session.It recovered during the post bed rest sessions.Conclusion The laryngopharyngeal reflux was found in the Pre,During and Post HDTBR experiment.The incidence was significantly increased both in the BR3 and R7 sessions,which indicates that the change of the posture with the stimulation of gastrointestinal dynamic conditions,despite the changes from vertical to horizontal or from horizontal to vertical,might be the major impact factor contributing to the elevation tendency of the incidence of laryngopharyngeal reflux.

Objective:To investigate the clinical efficacy of laparoscopic sleeve gastrec-tomy (LSG) in the treatment of obesity associated nonalcoholic fatty liver disease (NAFLD).Methods:The retrospective and descriptive study was conducted. The clinical data of 40 patients with obesity associated NAFLD who were admitted to Xijing Hospital of Digestive Diseases of Air Force Medical University from January 2018 to June 2019 were collected. There were 19 males and 21 females, aged (27±8)years. Patients underwent LSG after preoperative examinations and evaluations. Observation indicators: (1) surgical and postoperative conditions; (2) follow-up. Follow-up was conducted by telephone interview, WeChat, and outpatient review to detect the liver function, glucose and lipid metabolism-related status as well as the relief of comorbidities of patients at 6 and 12 months after LSG. The follow-up was up to June 2020. Measurement data with normal distribu-tion were represented as Mean± SD. Repeated measurement data were analyzed by the repeated measures ANOVA. Count data were represented as absolute numbers, and chi-square test was used for comparison between groups. Results:(1) Surgical and postoperative conditions: 40 patients underwent LSG successfully, without intraoperative conversion to laparotomy or death. The operation time, volume of intraoperative blood loss, and duration of postoperative hospital stay were (83±12)minutes, (19±7)mL and (3.7±0.7)days. Among the 40 patients, 1 case had fat liquefac-tion after LSG and 2 had abdominal distension within a month, who were improved after symp-tomatic and supportive treatment. (2) Follow-up: 40 patients were followed up at postoperative 6 and 12 months. The body mass of 40 patients was (112±17)kg, (85±16)kg, (73±11)kg before operation, at postoperative 6 and 12 months, respectively. The body mass index was (39.7±4.2)kg/m 2, (30.0±4.5)kg/m 2, (25.9±2.9)kg/m 2 before operation, at postoperative 6 and 12 months, respectively. The alanine aminotransferase was (56.40±39.51)U/L, (30.15±17.93)U/L, (26.45±9.44)U/L before operation, at postoperative 6 and 12 months, respectively. The aspartate amino-transferase was (34.03±19.62)U/L, (28.20±10.27)U/L, (24.90±8.44)U/L before operation, at post-operative 6 and 12 months, respectively. The gamma-glutamyltransferase was (48.68±28.45)U/L, (43.30±18.56)U/L, (32.80±12.09)U/L before operation, at postoperative 6 and 12 months, respectively. The fasting blood-glucose was (6.51±2.38)mmol/L, (5.64±1.51)mmol/L, (4.98±0.91)mmol/L before operation, at postoperative 6 and 12 months, respectively. The triglyceride was (1.81±0.95)mmol/L, (1.48±0.57)mmol/L, (1.17±0.44)mmol/L before operation, at postoperative 6 and 12 months, respectively. The total cholesterol was (4.77±0.98)mmol/L, (4.58±0.75)mmol/L, (4.10±0.68)mmol/L before operation, at postoperative 6 and 12 months, respectively. The low density lipoprotein cholesterin was (2.99±0.81)mmol/L, (2.79±0.54)mmol/L, (2.48±0.40)mmol/L before operation, at postopera-tive 6 and 12 months, respectively. The high density lipoprotein cholesterin increased was (1.08±0.20)mmol/L, (1.15±0.18)mmol/L, (1.45±0.21)mmol/L before operation, at postoperative 6 and 12 months, respectively. Compared with preoperative indicators, there were significant differences in postoperative body mass, body mass index, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, fasting blood-glucose, triglyceride, total cholesterol and low density lipoprotein cholesterin ( F=472.439, 533.730, 26.791, 11.029, 25.545, 27.994, 27.534, 36.220, 18.596, P<0.05), showing a downward trend. There was a significant difference between preoperative and postoperative high density lipoprotein cholesterin ( F=68.974, P<0.05), showing a upward trend. The excess weight loss of 40 patients at 6 months and 12 months after LSG were 61%±18% and 85%±15%. The preoperative ultrasonography of 40 patients showed no, mild, moderate and severe fatty liver in 0, 2, 15 and 23 cases, respectively. The above indicators were 8, 9, 12, 11 cases at post-operative 6 months, and 23, 11, 6, 0 cases at postoperative 12 months, respectively. There was a significant difference of the grade of NAFLD between patients before and after surgery ( χ2=68.210, P<0.05). Conclusion:LSG has an accurate short-term clinical efficacy for obesity associated NAFLD, which can reduce body mass, improve liver function, alleviat the disorders of glucose and lipid metabolism and the severity of medium-severe fatty liver.

Objective: To identify the time window during which the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway plays a key role in telogen-to-anagen transition of hair follicles, and to explore whether the pathway specifically promotes the proliferation of hair follicle stem cells (HFSCs) . Methods: Totally, 36 newborn ICR mice were randomly and equally divided into 3 groups: RAPA-P19 group intraperitoneally injected with 5 mg·kg^-1·d^-1 sirolimus on days 19-24 after birth, RAPA-P21 group intraperitoneally injected with 5 mg·kg^-1·d^-1 sirolimus on days 21-24 after birth, and control group intraperitoneally injected with the same volume of solvent on days 19-24 after birth. Four mice were sacrificed in each group on days 22, 23 and 24 separately. Skin tissues were resected from the back, and hematoxylin-eosin staining of the skin tissues were performed followed by observation of hair follicle morphology to evaluate whether murine hair follicles progressed into the anagen phase on day 24. Immunofluorescence costaining was conducted to determine the expression and localization of mTORC1 downstream molecular marker pS6 and cell proliferation marker Ki67 on days 22 and 23. Results: On day 24, hematoxylin-eosin staining showed anagen hair follicles in the control group and RAPA-P21 group, but telogen hair follicles in the RAPA-P19 group. On days 22 and 23, immunofluorescence costaining revealed positive staining for both pS6 and Ki67 in HFSCs in the control group, negative staining for both pS6 and Ki67 in the RAPA-P19 group, negative staining for pS6 and positive staining for Ki67 in the RAPA-P21 group. On day 23, epidermal cells and sebaceous gland cells in the upper hair follicle bulge were stained positively for Ki67 in all the 3 groups. Conclusion mTORC1 signaling specifically promotes the proliferation of HFSCs during telogen-to-anagen transition, but not affects proliferation of other cells in hair follicles.