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

Objective:Glioblastoma(GBM)and brain metastases(BMs)are the two most common malignant brain tumors in adults.Magnetic resonance imaging(MRI)is a commonly used method for screening and evaluating the prognosis of brain tumors,but the specificity and sensitivity of conventional MRI sequences in differential diagnosis of GBM and BMs are limited.In recent years,deep neural network has shown great potential in the realization of diagnostic classification and the establishment of clinical decision support system.This study aims to apply the radiomics features extracted by deep learning techniques to explore the feasibility of accurate preoperative classification for newly diagnosed GBM and solitary brain metastases(SBMs),and to further explore the impact of multimodality data fusion on classification tasks. Methods:Standard protocol cranial MRI sequence data from 135 newly diagnosed GBM patients and 73 patients with SBMs confirmed by histopathologic or clinical diagnosis were retrospectively analyzed.First,structural T1-weight,T1C-weight,and T2-weight were selected as 3 inputs to the entire model,regions of interest(ROIs)were manually delineated on the registered three modal MR images,and multimodality radiomics features were obtained,dimensions were reduced using a random forest(RF)-based feature selection method,and the importance of each feature was further analyzed.Secondly,we used the method of contrast disentangled to find the shared features and complementary features between different modal features.Finally,the response of each sample to GBM and SBMs was predicted by fusing 2 features from different modalities. Results:The radiomics features using machine learning and the multi-modal fusion method had a good discriminatory ability for GBM and SBMs.Furthermore,compared with single-modal data,the multimodal fusion models using machine learning algorithms such as support vector machine(SVM),Logistic regression,RF,adaptive boosting(AdaBoost),and gradient boosting decision tree(GBDT)achieved significant improvements,with area under the curve(AUC)values of 0.974,0.978,0.943,0.938,and 0.947,respectively;our comparative disentangled multi-modal MR fusion method performs well,and the results of AUC,accuracy(ACC),sensitivity(SEN)and specificity(SPE)in the test set were 0.985,0.984,0.900,and 0.990,respectively.Compared with other multi-modal fusion methods,AUC,ACC,and SEN in this study all achieved the best performance.In the ablation experiment to verify the effects of each module component in this study,AUC,ACC,and SEN increased by 1.6%,10.9%and 15.0%,respectively after 3 loss functions were used simultaneously. Conclusion:A deep learning-based contrast disentangled multi-modal MR radiomics feature fusion technique helps to improve GBM and SBMs classification accuracy.

Objective:To investigate the clinical effects of adjustable external fixation traction combined with arthroscopic microfracture in the treatment of osteochondral lesions of the talus (OLT).Methods:A retrospective study was conducted to analyze the data of 27 OLT patients who had been treated at Department of Orthopedics, Beijing Rehabilitation Hospital from May 2017 to March 2022. There were 16 males and 11 females, aged (32.4±7.2) years. Lesion site: 23 medial and 4 lateral cases; Hepple staging: 7 cases at stage Ⅰ, 15 cases at stage Ⅱ, and 5 cases at stage Ⅲ; disease duration: (10.6±3.3) months. All the patients were treated by adjustable external fixation traction combined with arthroscopic microfracture. Recorded were the patients' visual analogue scale (VAS) pain scores and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores at 6 months and 12 months after surgery, levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor- α (TNF- α) at 1 month after surgery, lesion area at 12 months after surgery, and incidence of complications. Results:The follow-up time for this cohort was (16.2±6.7) months. The AOFAS score was (61.52±6.75) points before surgery, (84.15±5.56) points at 6 months after surgery and (95.67±4.30) points at 12 months after surgery. The VAS score was (5.88±1.02) points before surgery, (2.12±0.48) points at 6 months after surgery and (0.66±0.36) points at 12 months after surgery. The two-by-two comparisons between the 3 time points for the above items were statistically significant ( P<0.05). IL-1 was (32.37±6.64) pg/mL, IL-6 (34.04±7.12) pg/mL, and TNF- α (17.89±4.96) ng/L at 1 month after surgery in the 27 patients, all of which were significantly lower than their preoperative levels [(96.63±14.80) pg/mL, (102.33±20.42) pg/mL, and (54.48±9.33) ng/L] ( P<0.05). The lesion area was (28.66±6.52) mm 2 at 12 months after surgery, significantly smaller than the value before surgery [(128.52±11.32) mm 2] ( P<0.05). Infection at the adjustable external fixation needle track occurred in 1 patient and lower limb thrombosis in 2 patients. Conclusion:In the treatment of OLT, adjustable external fixation and traction combined with arthroscopic microfracture can achieve satisfactory results and improve symptoms for the patients.

Objective To investigate the role and mechanism of silent information regulator 1(SIRT1)-NOD-like receptor protein 3(NLRP3)axis in the effect of remifentanil against ischemia-reperfusion injury(IRI)in rat livers.SD rats were randomly divided into sham operation group(sham group),IRI group,IRI+remifentanil pretreatment group(IRI+RPC group),IRI+SIRT1 inhibitor EX-527 group(IRI+EX-527 group)and IRI+RPC+EX-527 group,with 8 rats in each group.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH),interleukin(IL)-1β and IL-18 of rats in each group were detected.The liver tissue pathology was observed.The apoptosis rate of hepatocytes in rats was detected.The expressions of SIRT1,NLRP3,cleaved cysteinyl aspartate specific proteinase-1(Cleaved Caspase-1)and Gasdermin D(GSDMD)proteins in rat liver tissue were detected.Results Compared with the sham group,the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI group were increased,the serum ALT,AST,LDH,IL-1β,and IL-18 levels were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Compared with the IRI group,the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+RPC group were decreased,the serum ALT,AST,LDH,IL-1β,and IL-18 levels were decreased,the relative expression of SIRT1 protein in liver tissue was increased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were decreased;the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+EX-527 group were increased,the ALT,AST,LDH,IL-1β,and IL-18 levels were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Compared with the IRI+RPC group,the liver tissue pathological score and hepatocyte apoptosis rate in the IRI+RPC+EX-527 group were increased,the levels of ALT,AST,LDH,IL-1β,and IL-18 were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Conclusions SIRT1 may participate in the regulation of remifentanil against rat liver IRI by inhibiting NLRP3 mediated cell pyroptosis.

Necroptosis is a regulated process of programmed cell death independent of aspartic acid-specific cysteine protease,which can induce inflammation.Studies have shown that necroptosis is closely related to the progression and prognosis of pancreatic disease and plays an important two-way regulatory role in its progression.Related necroptosis inhibitors and inducers are expected to be used in the treatment of pancreatic disease.We herein review the mechanism of necroptosis and its role in the progression of pancreatic disease to provide a new understanding of the pathogenesis and treatment of pancreatic diseases and offer a theoretical basis for the research and development of targeted drugs.

Prostate cancer is a prevalent malignant tumor in the male genitourinary system,characterized by a high propensity for bone metastasis.It is a leading cause of mortality,with approximately 70％of deaths attributed to this form of metastasis.Mouse models provide a crucial tool in the investigation of prostate cancer bone metastasis,and play a pivotal role in elucidating the underlying pathophysiological mechanisms and in the development and assessment of therapeutic agents.In this review,we summarize research progress in the construction method and evaluation strategies used in establishing prostate cancer bone metastasis mouse models.Notably,this review focuses on the exploration of the mechanisms responsible for prostate cancer bone metastasis,using mouse models,with the aim of offering insights and serving as a valuable reference for prostate cancer bone metastasis.

Objective:To explore the effects of a structured exercise intervention on the healthy physical fitness in patients with leukemia receiving umbilical cord blood transplantation.Methods:It was a randomized controlled trial, conducted from August 2022 to October 2023 at the Department of Hematology of the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital). Fifty leukemia patients undergoing umbilical cord blood transplantation were recruited and were randomly assigned to either the control group (24 cases) or the intervention group (26 cases) using a random number table method. The control group received routine nursing care, health education, and exercise guidance during hospitalization. The intervention group were given moderate-intensity structured exercise intervention, including aerobic, resistance exercises, and flexibility training, three times per week for 30 to 40 minutes per session, over a period of 6 to 8 weeks. During the study, 2 patients withdrew due to disease reasons, and finally, 22 patients in the control group and 26 patients in the intervention group were obtained. The paired t-test, Wilcoxon test, and covariance analysis were used to compare the indices of healthy physical fitness before and after the intervention between the two groups, aiming to explore the effects of a structured exercise intervention on the healthy physical fitness of leukemia patients undergoing umbilical cord blood transplantation. Results:Before the intervention, there was no significant differences in baseline characteristics, such as age, gender and disease status between the two groups (all P>0.05). During the hospitalization phase, the rate of exercise participation in the intervention group was 73.4%, the frequency of exercise was (2.20±0.41) sessions per week and the duration of each exercise session was (34.34±5.05) minutes, and the Borg′s rating of perceived exertion was (13.04±0.82) points. After intervention, the indicators including cardiovascular endurance, muscle fitness, and functional activity status in the two groups were all decreased, and the reduction degree of the indicators were all significantly lower in the intervention group when compared with those in the control group [6-minute walk distance (48.81±30.39) m vs (143.05±77.26) m, grip strength of left hand (2.57±1.30) kg vs (6.72±4.88) kg, grip strength of right hand (2.47±1.97) kg vs (6.34±5.70) kg, muscle strength of left upper limb (4.12±2.07) times vs (8.18±5.26) times, muscle strength of right upper limb (3.96±2.29) times vs (7.91±5.16) times, 30 second chair standing test (3.65±1.98) times vs (7.86±4.34) times, and timed-up-and-go test (0.65±0.53) s vs (2.35±1.79) s] (all P<0.05). The flexibility fitness was improved in the intervention group after the intervention [sit-and-reach 2.00(-4.75, 8.18) cm vs 0(-9.75, 6.43) cm] ( P=0.011), but no significant differences was found in the control group ( P>0.05). Conclusions:The structured exercise intervention has advantages in reducing the decline of healthy physical fitness in patients with leukemia receiving umbilical cord blood transplantation, and exerts a protective effect on healthy physical fitness.

Objective:To investigate the clinical effects of tibial transverse bone transport assisted by nose ring drainage (NRD) in the treatment of foot and ankle chronic osteomyelitis.Methods:A retrospective study was conducted to analyze the data of 32 patients with foot and ankle chronic osteomyelitis who had been treated at Department of Orthopedics, Beijing Rehabilitation Hospital from March 2013 to February 2022. The patients were assigned into a study group and a control group. In the control group, there were 12 males and 3 females, aged (39.5±8.8) years. The osteomyelitis was located at the distal tibia in 4 cases, at the talus in 1 case, at the calcaneus in 2 cases, at the midfoot in 4 cases and at the forefoot in 4 cases. According to the Crerny-Mader classification, there were 5 cases of type Ⅰ and 10 cases of type Ⅱ. The control group was treated with Ilizarov transverse tibial bone transport in combination with thorough debridement and anti-infection therapy. In the study group, there were 12 males and 5 females, aged (42.3±13.4) years. The osteomyelitis was located at the distal tibia in 4 cases, at the talus in 1 case, at the calcaneus in 3 cases, at the midfoot in 5 cases and at the forefoot in 4 cases. According to the Crerny-Mader classification, there were 7 cases of type Ⅰ and 10 cases of type Ⅱ. The study group was treated with NRD drainage in addition to the procedures in the control group. The curative effects were evaluated by comparing the cure, recurrence, amputation (toe amputation), antibiotic use time, wound healing time, relevant inflammatory indicators [WBC, neutrophil percentage (NEU), erythrocyte sedimentation rate (ESR), procalcitonin, interleukin-6 (IL-6), C-reactive protein (CRP)], and postoperative functional recovery between the 2 groups.Results:The 2 groups were comparable because there was no statistically significant difference in the general data between them ( P>0.05). The follow-up period was (36.0±9.8) months. There was no significant difference between the 2 groups in the cure or amputation (toe amputation) ( P>0.05), but the recurrence rate in the study group was significantly lower than that in the control group ( P<0.05). The antibiotic use time [(20.7±3.6) d] and wound healing time [(88.3±17.1) d] in the study group were significantly shorter than those [(37.9±6.5) d and (102.2±22.6) d] in the control group ( P<0.05). The ESR, IL-6 and CRP at 1 week after operation in the study group were significantly lower than those in the control group ( P<0.05), but there was no significant difference between the 2 groups in the WBC, NEU or PCT at 1 week after operation ( P>0.05). There was no significant difference either in the inflammatory indicators between the 2 groups at 1 month after operation ( P>0.05). In all patients, the inflammatory indicators like WBC, NEU, ESR, PCT, IL-6 and CRP at 1 week and 1 month after operation were significantly better than those before operation, and the Maryland foot functional score at 12 months after operation was significantly higher than the preoperative one ( P<0.05). There was no significant difference between the 2 groups in the Maryland foot functional score at 12 months after operation ( P>0.05). Conclusion:In the treatment of foot and ankle chronic osteomyelitis, compared with the Ilizarov transverse tibial bone transport, our tibial transverse bone transport assisted by NRD can achieve satisfactory therapeutic effects, shorten antibiotic use time and treatment cycle, and reduce recurrence rate.

The clinical manifestation of iodine-refractory differentiated thyroid cancer (RAIR-DTC)is resistance to iodine therapy, which can not achieve the therapeutic effect and affect the prognosis of patients. Iodine-refractory thyroid cancer is mainly due to the decrease or disappearance of the expression of sodium-iodine isotransporters, the expression of some thyroid specific genes and the change of signaling pathway caused by some gene mutations. In this paper, the molecular characteristics of RAIR-DTC will be introduced and expounded, hoping to enhance understanding of RAIR-DTC, and provide help for targeted drug therapy of it.