Objective To explore the severity of loneliness among the elderly in communities in Shanghai,and to identify factors associated with social and emotional loneliness respectively.Methods A cross-sectional study was conducted in older adults aged 65 years or above in Pudong New Area,Jing'an District and Huangpu District in Shanghai from Mar to Jun 2021.In Pudong New Area,multi-stage stratified random sampling was conducted based on the age and gender distribution of Shanghai,while in Huangpu District and Jing'an District convenience sampling was conducted.A total of 635 samples were included in the study.Loneliness was assessed using the De Jong Gierveld Loneliness Scale with social and emotional loneliness subscales.Logistic regression analyses were conducted to identify factors associated with social and emotional loneliness.Results Among the 635 participants,only 53 older adults(8.4%)were not lonely.Female(OR=0.46,95%CI:0.31-0.70),higher self-efficacy(OR=0.97,95%CI:0.94-1.00),more objective social support(OR=0.96,95%CI:0.93-0.99)were associated with less severe social loneliness.Meanwhile,higher level of education(secondary education,OR=0.56,95%CI:0.34-0.95;college or above,OR=0.30,95%CI:0.11-0.83)and higher self-efficacy(OR=0.96,95%CI:0.93-0.99)were associated with less severe emotional loneliness,while depression(OR=3.41,95%CI:1.76-6.60)and worse social capital(OR=2.02,95%CI:1.29-3.16)were associated with more severe emotional loneliness.Conclusion Up to 91.6%of the elderly in our study sample were moderately lonely or above.The factors associated with social loneliness include self-efficacy,gender and social support.The factors associated with emotional loneliness are self-efficacy,education level,depression,and social capital.

Adenosine has been proved to have immunosuppressive effect in many different diseases, and the activity of ecto-5’-nucleotidase(CD73) on the cell surface is the rate-limiting step of extracellular adenosine production. CD73 has a profound and lasting impact on tumor immune regulation of regulatory T cells, B cells, macrophages and natural killer cells. CD73-mediated adenosine pathway is significant in signal transduction during cancer progression in tumor microenvironment, making CD73 a novel immune checkpoint. Therefore, CD73 inhibition is a emergent and promising strategy for cancer immunotherapy. At present, a variety of monoclonal antibodies and small molecule inhibitors have been in clinical development. This review comprehensively summarizes the frontier research progress of reported small molecule CD73 inhibitors, which can provide guidance for the investigation of novel CD73 inhibitors for cancer therapy.

Objective: Progressive supranuclear palsy (PSP) involves a variety of visual symptoms that are thought to be partially caused by structural abnormalities of the retina. However, the relationship between retinal structural changes, disease severity, and intracranial alterations remains unknown. We investigated distinct retinal thinning patterns and their relationship with clinical severity and intracranial alterations in a PSP cohort. Methods: We enrolled 19 patients with PSP (38 eyes) and 20 age-matched healthy controls (40 eyes). All of the participants underwent peripapillary and macular optical coherence tomography. Brain 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography imaging were also performed in patients with PSP. We investigated the association between retinal thickness changes and clinical features, striatal dopamine transporter availability, and cerebral glucose metabolism. Results: The peripapillary retinal nerve fiber layer (pRNFL) and macula were significantly thinner in patients with PSP than in controls. The thickness of the superior sector of the pRNFL demonstrated a significant negative relationship with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III and Hoehn and Yahr staging scale scores. A significant negative correlation was found between outer inferior macular thickness and disease duration. Outer temporal macular thickness was positively correlated with Montreal Cognitive Assessment scores. In PSP, lower outer temporal macular thickness was also positively correlated with decreased dopamine transporter binding in the caudate. Conclusion The pRNFL and macular thinning may be candidate markers for monitoring disease severity. Additionally, macular thinning may be an in vivo indicator of nigrostriatal dopaminergic cell degeneration in PSP patients.

Adult ; Humans ; Acute Disease ; Leukemia

Objective:To compare the therapeutic effect of one-stage versus two-stage percutaneous transhepatic biliary fistulation lithotripsy in treatment of complex hepatolithiasis.Methods:A retrospective study was conducted on 145 patients with complex hepatolithiasis who were treated at the First Affiliated Hospital of Guangzhou Medical University between September 2013 and June 2018. There were 60 males and 85 females, aged 21 to 91 (56.5±14.1) years. According to the method of fistula establishment, patients were divided into the percutaneous transhepatic one-step biliary fistulation (PTOBF) group ( n=94) or the two-stage percutaneous transhepatic choledochoscopic lithotripsy (PTCSL) group ( n=51). The success rates of one-time puncture and fistula dilation, operation time of lithotripsy, operative conversion rate (PTCSL was converted to laparotomy and laparoscopic surgery), postoperative complications (including catheter dislodgement), residual stone rates and stone recurrence rates were compared between groups. Results:In the PTOBF group, operation time (105.8±43.6) min, success rate of one puncture 73.4% (69/94), and success rate of one fistula dilation 93.6% (88/94), the rate of operative conversion 0. All these results were significantly better than the corresponding results of the two-stage PTCSL group of (130.0±70.0) min, 54.9% (28/51), 68.6% (35/51), and 13.7%(7/51) respectively (all P<0.05). There were no significant differences in stone residual rate [17.0%(16/94) vs. 15.7% (8/51)] and stone recurrence rate [14.9%(14/94) vs. 17.6% (9/51)] between groups (both P>0.05). The postoperative complications rate was 7.4%(7/94) in PTOBF group, which was 39.2% (20/51) in two-stage PTCSL group (χ 2=22.02, P<0.001). The catheter dislodgement rate of PTOBF group was 2.1% (2/94), lower than that of two-stage PTCSL group 27.4% (14/51), the difference was statistically significant (χ 2=21.59, P<0.001). Conclusion:One-stage PTOBF and two-stage PTCSL were both safe and effective in treatment of complex hepatolithiasis. However, PTOBF had shorter operative times, lower catheter dislodgement and operative conversion rates than PTCSL.

Impaired healing of diabetic wounds is mainly attributed to its pathological mechanism, and refractory diabetic wounds bring heavy burdens to patients and society. Exosomes derived from stem cells possess the similar ability as stem cells in promoting tissue regeneration and more clinical advantages and are gradually playing important roles in wound healing. In recent years, researches have shown that exosomes derived from adipose-derived mesenchymal stem cells (ADSC-EXOs) can promote the healing of diabetic wounds by participating in various processes of wound healing. This article reviews the pathological mechanism leading to impaired healing of diabetic wounds, the related mechanism and the application prospect of ADSC-EXOs in promoting diabetic wound healing.
Diabetes Mellitus ; Exosomes ; Humans ; Mesenchymal Stem Cells ; Stem Cells ; Wound Healing

OBJECTIVE: To investigate the changes in autophagy of mesenchymal stem cells (MSCs) from patients with ankylosing spondylitis and explore the mechanism for decreased autophagy in ASMSCs. METHODS: MSCs collected from 14 patients with AS (ASMSCs) and from 15 healthy donors (HDMSCs) were cultured in the absence or presence of 25 ng/mL TNF-α for 6 h. Autophagy of the cells was determined by immunofluorescence staining of GFP-LC3B, and the results were confirmed by detecting the protein expressions of autophagy markers LC3 II/LC3 I and P62. The mRNA expressions of the related genes were detected using qRT-PCR, and the protein expressions of the autophagy markers and signaling pathway-related molecules were determined with Western blotting. TG100713 was used to block the PI3K/AKT/mTOR signal pathway, and its effect on autophagy of ASMSCs was evaluated. RESULTS: ASMSCs showed significantly weaker GFP-LC3B puncta staining and lower protein expression levels of LC3 II/LC3 I but higher levels of P62 protein (P < 0.05), indicating a decreased autophagy capacity as compared with HDMSCs. TNF-α-induced ASMSCs showed significantly higher protein expressions of p-PI3K/ PI3K, p-AKT/AKT and p-mTOR/mTOR than HDMSCs (P < 0.05), suggesting hyperactivation of the PI3K/AKT/mTOR signaling pathway in ASMSCs. Blocking PI3K/AKT/mTOR signaling with TG100713 eliminated the difference in TNF-α-induced autophagy between HDMSCs and ASMSCs. CONCLUSION In patients with AS, hyperactivation of the PI3K/AKT/mTOR signaling pathway results in decreased autophagy of the MSCs and potentially contributes to chronic inflammation.
Autophagy ; Humans ; Mesenchymal Stem Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Spondylitis, Ankylosing ; TOR Serine-Threonine Kinases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Objective - To investigate the effect of lung flora dysbiosis on the process of pulmonary fibrosis and lung epithelial （ ） Methods - mesenchymal transition EMT in mice with silicosis. Male C57BL/6 mice of specific pathogen free grade were ， ， ， （ ） randomly divided into the blank control group silicosis model group solvent control group vancomycin VM + ampicillin （ ） ， （ ） （ ） ， AMP group metronidazole MNZ + neomycin NEO group and mixed treatment group 12 mice in each group. Except for ， ， the blank control group which was given 20.0 µL of 0.9% NaCl solution the other five groups of mice were dosed with 20.0 µL of silica dust suspension at a mass concentration of 250.0 g/L using a single tracheal drip to establish the silicosis mouse model. ： The intranasal drip method was used to treat silicosis mice in each group as following mice in the solvent control group were - ； ； given double distilled water mice in the VM+AMP group were given VM at a mass concentration of 0.5 g/L and AMP at 1.0 g/L ； mice in the MNZ+NEO group were given MNZ at a mass concentration of 1.0 g/L and NEO at 1.0 g/L mice in the mixed ， treatment group were given the same doses of the four antibiotics mentioned above all in a drip volume of 50.0 µL. Silicosis ， ， mice were treated seven days and half an hour before silica dusting and 7 14 and 21 days after silica dusting. Mouse lungtissue was collected aseptically 28 days after silica dusting. Hematoxylin eosin and Masson trichrome staining methods were - used to observe the pathological changes. Western blotting was used to detect the relative protein expression of α smooth muscle （ - ）， - （ - ） （ ） actin α SMA E cadherin E CAD and vimentin VIM . Immunohistochemistry was used to detect the relative expression of - - E CAD and VIM. Real time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of （Col1a2） Results collagen type Ⅰ alpha 2 mRNA in lung tissues. The histopathological results showed that the alveoli of the ， blank control group were thin and structurally intact with few surrounding infiltrating inflammatory cells and no abnormal ， distribution of collagen fibers. The alveoli of the silicosis model group were structurally disorganized with a large number of ， ， infiltrating inflammatory cells thickened alveolar walls and cellular fibrous nodules with abundant blue collagen deposit. In the ， ， VM+AMP group MNZ+NEO group and the mixed treatment group the inflammation and fibrosis were reduced with diferent degrees in the lung tissues compared to the silicosis model group and the solvent control group. The relative expression levels of - ， Col1a2 α SMA VIM protein and mRNA in lung tissues of mice in the silicosis model group were higher than those in the blank （ P ）， -CAD control group all <0.05 and the relative expression levels of E protein were lower than those in the blank control （P ） - ， Col1a2 group <0.05 . The relative expression levels of α SMA VIM protein and mRNA in lung tissues of mice in the MNZ+ （ P ）， -CAD NEO group and the mixed treatment group were lower all <0.05 and the relative expression levels of E protein were （P ）， Conclusion higher <0.05 when compared with the silicosis model group and the solvent control group. Pulmonary fibrosis ， - was reduced in silicosis mice with interventions in lung flora where anaerobic and gram negative bacteria affected pulmonary fibrosis and dysbiosis of the lung flora affected pulmonary EMT.

Acupoint is the initial response site of acupuncture stimulus and also the source link of the effect onset of acupuncture. Acupuncture is a mechanical physical stimulus. How is the mechanical force of acupuncture transduced into neuroelectrical and biochemical signals at acupoint? How does the physiochemical information of acupoint launch acupuncture effect? All of these remain the common and crucial questions in the study of acupuncture effect mechanism. Physical changes are induced in the local tissue of acupoint by needling techniques, such as the deformation and displacement of muscle fibers, which may act on the nerve ending receptors and produce electroneurographic signals. Besides, these changes may activate the mechanosensitive ion channels of the cytomembrane in acupoint site. Through cellular signal transduction, the physical signals may be transformed into chemical ones to trigger the physiochemical coupling response of acupoint microenvironment. Eventually, acupuncture effect is generated via nerves and body fluids. "The mechanical force of acupuncture", through "the physiochemical transduction", promotes the body's perception and transmits acupuncture signals. It suggests that acupoint is the "transducer" in the physiochemical information coupling response of acupuncture.
Acupuncture Therapy ; Acupuncture Points