Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

Attempts have been made to modulate motor sequence learning (MSL) through repetitive transcranial magnetic stimulation, targeting different sites within the sensorimotor network. However, the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified. This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper (SMAp) in modulating MSL across different complexity levels and for both hands, as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation. Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL, which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions, particularly in interhemispheric connections. These findings may have important clinical implications, particularly for motor rehabilitation in populations such as post-stroke patients.
Humans ; Transcranial Magnetic Stimulation ; Motor Cortex/physiology* ; Male ; Electroencephalography ; Neuronal Plasticity/physiology* ; Female ; Adult ; Evoked Potentials, Motor/physiology* ; Young Adult ; Learning/physiology*

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Objective To discuss the application of using transulnar approach(TUA),which is used as a complementary approach,after failure of transradial approach(TRA)in performing neurointerventional surgery,and to evaluate its clinical safety and feasibility.Methods A total of 189 consecutive patients,who were admitted to the Department of Neurointerventional Surgery,Affiliated Hospital of Binzhou Medical University of China from January to August of 2023 to receive treatment,were retrospectively collected.Of the 189 patients receiving neurointerventional surgery using TRA,23 adopted TUA puncture after failure of TRA puncture.The clinical data and the surgical materials were retrospectively collected.The diameter and depth of the radial artery and ulnar artery were measured by Doppler ultrasound before the operation.A 6 F catheter sheath was used to establish intraoperative manipulation access.After treatment,Doppler ultrasonography was used to assess the occurrence of arterial puncture-related complications and the patency of artery.The technical success rate and the puncture-related complications of TUA in neurointerventional surgery were calculated and analyzed.Results All the 23 patients underwent neurointerventional surgery.The preoperative mean ulnar artery diameter of the forearm and the depth of the ulnar radial artery measured by Doppler ultrasound were(2.1±0.3)mm and(5.6±1.0)mm respectively.The success rate of using TUA after failure of TRA for neurointerventional surgery was 91.3％(21/23)and no additional re-disinfection was required during the same procedure.In 2 patients,transfemoral artery approach(TFA)was used after failure of TUA.The causes of TUA failure included failure of guide wire insertion due to repeated puncturing(n=1)and failure of catheterization due to severe pain(n=1).Postoperative forearm angiography with manual-push injection method demonstrated that ulnar artery spasm occurred in S patients(34.8％).Postoperative re-examination of Doppler ultrasonography showed that no diminished pulse of the ulnar artery or hand ischemia was observed.One patient developed fat liquefaction at the puncture site,two patients developed hematoma around the puncture point,and one patient experienced transitory numbness around the puncture point.Thirty days after treatment,the follow-up check with Doppler ultrasonography showed that no ulnar artery occlusion was observed.Conclusion During the performance of neurointerventional surgery,the use of TUA after failure of TRA,which is used as a complementary approach,is clinically safe and feasible.However,because TUA carries several certain technical difficulties such as puncturing,catheterization,deeper position and smaller diameter of ulnar artery,diffuse arterial pulsation,etc.the operators need to go through a long learning curve before his or her puncturing success rate of ulnar artery can be surely improved.

Objective : To analyze the distribution characteristics of free water ( FW) and FW-corrected fractional anisotropy (FAt) in the white matter of the brain in patients with anti-N-methyl-D-aspartate receptor ( NMDAR) encephalitis and to explore their correlation with cognitive function． Methods : A total of 38 patients with anti- NMDAR encephalitis and 30 controls were recruited from three hospitals in Hefei．Diffusion tensor imaging data and neuropsychological assessment results were collected．Tract-Based Spatial Statistics was applied to compare group differences in FW and FAt across the whole brain white matter．Correlation analyses were further performed to ex- amine the relationships between FW/ FAt metrics and cognitive function． Results : Compared to the control group， patients with anti-NMDAR encephalitis showed significantly lower scores on the montreal cognitive assessment，im- mediate recall，delayed recall，and the verbal fluency test (all P＜0. 05) ，as well as significantly longer comple- tion times for color naming and word reading tasks in the stroop color word test (all P＜0. 05) ．Diffusion tensor im- aging analysis revealed significantly elevated FW and reduced FAt in widespread white matter regions in the patient group (all P＜0. 000 1) ．Further correlation analysis showed that increased FW was positively associated with the completion time of the color-switching condition in the color digital trail making test (P = 0. 044 ) and with the difference between color-switching and number sequencing conditions ( P = 0. 016 ) ，while negatively correlated with semantic fluency scores (P = 0. 002) ．Additionally，FAt was positively associated with delayed recall perform- ance (P = 0. 012) ，and negatively correlated with the completion times for color naming (P = 0. 018 ) and word reading (P = 0. 046) tasks in the SCWT． Conclusion Patients with anti-NMDAR encephalitis exhibit significantly elevated FW and significantly reduced FAt in white matter tracts，both of which are closely linked to cognitive im- pairment．

Cellular senescence, stable cell cycle arrest that can be triggered in normal cells in response to various intrinsic and extrinsic stressors, has been highlighted as one of the most important mechanisms involved in kidney diseases. It not only serves as a fundamental biological process promoting normal organogenesis and successful wound repair but also contributes to organ dysfunction, tissue fibrosis, and the generalized aging phenotype. Moreover, senescent cells exhibit reduced regenerative capacity, which impairs renal function recovery from injuries. Importantly, senescent cells are involved in immune regulation via secreting a diverse array of proinflammatory and profibrotic factors known as senescence-associated secretory phenotype (SASP) with autocrine, paracrine, and endocrine activities. Thus, eliminating detrimental senescent cells or inhibiting SASP production holds great promise for developing innovative therapeutic strategies for kidney diseases. In this review, we summarize the current knowledge of the intricate mechanisms and hallmarks of cellular senescence in kidney diseases and emphasize novel therapeutic targets, including epigenetic regulators, G protein-coupled receptors, and lysosome-related proteins. Particularly, we highlight the recently identified senotherapeutics, which provide new therapeutic strategies for treating kidney diseases.
Humans ; Cellular Senescence/genetics* ; Kidney Diseases/pathology* ; Senescence-Associated Secretory Phenotype/physiology* ; Animals ; Epigenesis, Genetic/physiology*

Objective To evaluate the efficacy of proximal femoral universal nail(PFUN),a new type of intramedullary fixation system,in the treatment of acute unilateral intertrochanteric femoral fracture in elderly patients.Methods From January 2022 to January 2024,200 patients with acute unilateral femoral intertrochanteric fracture were treated in our department.After closed traction reduction,PFUN was implanted with small incisions.Unified rehabilitation plan was adopted after surgery.The functional evaluation was performed by using the Harris hip score system at the last follow-up.Results The operation time was 25-182 min(median,63.0 min).The intraoperative blood loss was 10-750 ml(median,50.0 ml).Intraoperative blood transfusion(suspension of red blood cells)was required in 40 cases(20％).The postoperative hospital stay was 1-15 d(mean,4.0±1.9 d).The postoperative femoral neck-shaft angle was 116.7°-140.1°(mean,132.4°±5.5°).The quality of fracture reduction on the first day after surgery showed 140 cases as excellent,54 cases acceptable,and 6 cases poor.Complications occurred in 13 cases,including superficial wound infection in 2 cases,who were cured by regular wound dressing change and antibiotic treatment,lower extremity deep vein thrombosis in 8 cases,who were given low molecular weight heparin anticoagulation treatment until improvement,pneumonia in 2 cases and urinary tract infection in 1 case,who were cured or improved after specialist treatment.At one month after surgery,the hip joint X-ray showed blurred fracture lines,callus formation at the fracture site,and no internal fixation failure.There was no internal fixation failure within 3 months after surgery.At six months after surgery,all fractures achieved healing without any failure of internal fixation.All the 200 cases were followed up for 12-29 months(mean,16.1±2.7 months).One case experienced internal fixation failure,and underwent head and neck screw resection,internal fixation removal and hip replacement.At the last follow-up,the postoperative recovery was satisfactory.The Harris score of hip joint was 70-94 points(mean,88.8±2.8 points),including 103 cases as excellent,92 cases good,and 5 cases fair,with an excellent and good rate of 97.5％(195/200).Conclusion PFUN is effective in the treatment of intertrochanteric femoral fractures in elderly patients,with reliable fixation,rapid postoperative recovery,and low failure rate of internal fixation,especially suitable for unstable cases with internal or external wall fractures.

Objective:The aim of this study was to explore the risk factors that affect implementation of the innovative technique of single-incision laparoscopic appendectomy (solo-SLA) without assistance in patients with complicated appendicitis, the goal being improving surgical success rates and reducing the incidence of complications.Methods:This was an observational study. Indications for solo-SLA surgery were as follows: (1) computed tomography or ultrasound findings suggestive of acute appendicitis, accompanied by a high white blood cell count and C-reactive protein concentration; (2) disease course exceeding 72 hours, standard anti-infection treatment ineffective, inflammatory reaction not localized, surgery mainly aimed at abscess drainage, and the appendix removed if indicated intraoperatively; (3) acute onset stabilized for more than 3 months after conservative treatment; and (4) recurrent chronic appendicitis. Relative contraindications comprised: (1) cardiopulmonary insufficiency, extremely high risk for general anesthesia for laparoscopic surgery; (2) severe coagulation dysfunction; and (3) imaging findings suggestive of formation of a peri-appendiceal abscess, stable after anti-infection treatment, and a tendency for the inflammatory reaction to localize. We retrospectively collected clinical data of 106 patients with complicated appendicitis who had undergone solo-SLA in the Department of Emergency Surgery, Peking University People's Hospital from February to October 2023. Preoperative computed tomography showed appendiceal fecaliths, blurring of the tissue surrounding fat, intra- and extra-luminal gas and exudate, peri-appendiceal abscess, ascites, and intestinal obstruction by appendicitis. The study cohort comprised 53 male and 53 female patients aged (41.4±17.4) years. The median body mass index was (24.2±3.6) kg/m 2 and median preoperative body temperature (37.3±0.9)℃ Appendicitis had been present for >3 days in 21 of the patients (19.8%) and the maximum diameter of the appendix was (12.4±3.8) mm. The efficacy of the surgery was assessed and logistic regression analysis used to explore the factors affecting the duration of the procedure. The relationship between the maximum diameter of the appendix and duration of surgery was non-linear and was explored using a logistic regression model with restricted cubic spline (RCS). Results:Only one patient required conversion to open surgery; all the other patients successfully completed solo-SLA with a median intraoperative blood loss of 10 (1-100) ml and a surgical time of (65.4±31.7) minutes. Pain scores on postoperative Day 1 and 7 were (3.4±3.2) points and (1.5±1.7) points, respectively. There were no significant postoperative complications .The postoperative hospital stay was (3.5±1.5) days and the interval to resuming normal activities 14 (2-40) days. According to univariate and multivariate analyses, disease course >3 days (OR=5.19, 95%CI: 1.59-16.98, P=0.006) and C-reactive protein >10 mg/L (OR=1.01,95%CI: 1.00-1.02, P=0.003) were independent risk factors for surgical duration >60 minutes, whereas the maximum diameter of the appendix was not independently associated with duration of surgery (OR=1.10, 95%CI: 0.97-1.25, P=0.119). RCS analysis results showed a "U-shaped" association between the maximum diameter of the appendix and duration of surgery, the inflection point of the RCS curve being at a diameter of 10 mm. When the maximum diameter of the appendix was <10 mm, increases in diameter were not associated with longer duration of surgery (OR=1.15,95%CI: 0.55-2.58, P=0.710); whereas when the diameter was ≥10 mm, the maximum diameter of the appendix was associated with increased duration of surgery (OR=1.20, 95% CI: 1.04-1.42, P=0.022). Conclusion:The solo-SLA procedure can be performed to treat complicated appendicitis. A disease course >3 days, C-reactive protein concentration >10 mg/L, and maximum diameter of the appendix ≥10 mm are all associated with greater difficulty of solo-SLA surgery.