Objective: To investigate whether acupoint penetration acupuncture (APA) could regulate chondrocyte autophagy and apoptosis via the PI3K/Akt-mTOR signaling pathway to reduce cartilage degeneration in knee osteoarthritis (KOA) rats. Methods: KOA was induced in rats via intra-articular injection of sodium iodoacetate resolution. Forty male Sprague-Dawley rats were randomly assigned to blank control, model, APA, electro-acupuncture (EA), and sham model groups (n = 8) and those in the APA and EA groups received their respective therapies. Following completion of the treatment course, histological examinations of cartilage and muscle were conducted. Levels of apoptosis- and autophagy-related factors, including Bax, Bcl-2, mTOR, ULK-1, and Beclin-1 protein, and mRNAs were assessed. Additionally, β-endorphin (β-EP) concentrations in the brain and serum were measured. Results: Histological analysis revealed that APA alleviated cartilage and muscle damage compared with the model group. APA inhibited cartilage degeneration by modulating the expression of apoptosis- and autophagy-related proteins and mRNA, thus preventing chondrocyte apoptosis. In the APA group, Bax and mTOR protein levels were significantly lower than those in the model group (both P = .024). Conversely, the Bcl-2 expression level was significantly higher than that in the EA group (P = .035). Additionally, ULK-1 expression was significantly lower than that in the EA group (P = .045). The mRNA level of Bax was significantly higher than that in the blank control group (P < .001). However, Beclin-1 levels were significantly higher than those in both the model and EA groups (both P < .001). ELISA results showed a significant decrease in the concentration of β-EP in the brains of the rats in the APA group compared with those in the model group (P = .032). Conclusions APA reduced osteoarthritis-related pain and alleviated cartilage damage by upregulating chondrocyte autophagy and down-regulating apoptosis via signaling pathways involving PI3K/Akt-mTOR in KOA rats.

This study systematically searches for academic papers related to metabolic and bariatric surgery between 2000 and 2023 through the Web of Science database, and uses biblio-metric methods and visualization techniques to deeply analyse research trends, leading researchers, research institutions, and hotspots in this field. Through analysis, it uncovers the research dynamics and cutting-edge advancements in metabolic and bariatric surgery. Additionally, the authors explore current research hotspots, challenges, and potential future research directions. This study not only provides valuable reference information for researchers in the field of metabolic and bariatric surgery, but also offers a scientific basis for clinical practice and policy making.

Objective:To document any effect of a pulsed electromagnetic field (PEMF) on the regulation of neuropeptide Y (NPY) in nucleus pulposus (NP) tissue, NP cell apoptosis and matrix degradation using rats with intervertebral disc degeneration (IDD).Methods:Eighteen Sprague-Dawley rats were randomly divided into a control group, an IDD model group (the model group), and a PEMF group. IDD was induced in both the model and PEMF groups. Right after the modeling, the PEMF group received 14 days of PEMF treatment, while the control group and model group were given no special treatment. Meanwhile, the primary rat nucleus pulposus cells (NPCs) were cultured using Dulbecco′s Modified Eagle Medium at 37℃ and 5% CO 2. When the fusion rate reached 90% after passage, the NPCs were divided into a control group, a TNF-α model group (referred to as model group) and TNF-α + PEMF group (referred to as PEMF group) and treated accordingly. Eight weeks after the modeling, safranin-o/fast green staining was used to assess any pathological morphology changes. The expression of NPY, neuropeptide Y receptor Y2 (NPY2R), bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), collagen type II (Col-II) and matrix metalloproteinase-3 (MMP3) in the intervertebral disc and the cultivated nucleus pulposus cells of the 3 groups were determined. Results:The intervertebral disc cells in the model group were ruptured and folded, with significantly increased polysaccharide and protein components, and significantly increased bone fibers. In the PEMF group the cell boundaries were clearer, with less fibrin fracture and increased cartilage tissue. NPY was expressed in the fibrous annulus and the nucleus pulposus of the intervertebral disc in the model group. The average expression levels of NPY and NPY2R were significantly higher than in the control group and the model group. Compared with the control group, there was a significant increase in the level of Bax and a significant decrease in the expression of Bcl-2 in the model group, and there was a significant decrease in the level of Bax in the PEMF group. Compared with the control group, there was a significant decrease in the Col-II level but a significant increase in the MMP3 protein expression in the model group. The average Col-II mRNA expression was significantly higher in the PEMF group compared with the model group, but the average MMP3 protein expression was significantly less. Those results are consistent with observations in vivo.Conclusion:PEMF may reverse the imbalance of ECM metabolism and delay IDD degeneration by up-regulating the expression of NPY and Bcl-2, as well as blocking the Bax/Bcl-2 signaling pathway to inhibit apoptosis of nucleus pulposus cells.

Objectives:To explore the clinical efficacy of applying the accurate foraminoplasty technique with visualized chisel under full-visualized spinal endoscopy(FVSE)in the treatment of lumbar disc herniation(LDH).Methods:The clinical data of 143 patients with single-segment LDH undergone operative treatment under FVSE in our hospital between July 2020 and December 2022 were retrospectively analyzed.63 cases were treated with the accurate framinoplasty technique with visualized chisel(Chisel group),consisting of 37 males and 26 females,aged 45.3±15.1 years(range,19-68 years),and body mass index(BMI)was 22.3± 1.8kg/m2(range,19.2-25.6kg/m2);Operative segment:L2/3 in 8 cases,L3/4 in 15 cases,L4/5 in 25 cases,L5/S1 in 15 cases;LDH anatomical classification:20 cases of bulging type,22 cases of protruding type,12 cases of prolapsing type,and 9 cases of free type;LDH location classification:10 cases of central type,21 cases of paracentral type,24 cases of foraminal type,and 8 cases of extreme lateral type.The other 80 cases were treated with trepan technique(Trephine group),consisting of 46 males and 34 females,aged 43.8±14.1 years(range,19-68 years),BMI was 21.5±1.6kg/m2(range,19.2-24.1kg/m2);Operative segment:L2/3 in 9 cases,L3/4 in 17 cases,L4/5 in 30 cases,and L5/S1 in 24 cases;LDH anatomical classification:23 cases of bulging type,31 cases of protruding type,19 cases of prolapsing type,7 cases of free type;LDH location classification:13 cases of central type,27 cases of paracentral type,29 cases of foraminal type,and 11 cases of extreme lateral type.The operative time,total intraoperative bleeding,number of fluoroscopies,and hospitalization time were recorded and compared between the two groups.The intervertebral foraminal area before operation,at 3d after operation and final follow-up,visual analogue scale(VAS)score,Oswestry disability index(ODI),and Japanese Orthopedic Association(JOA)score before operation,at postoperative 3d,1 month,6 months,and final follow-up were recorded and compared between the two groups.The clinical efficacy was assessed by MacNab criteria at the final follow-up.Results:The operative time,total intraoperative bleeding and number of fluoroscopies were 84.6±14.3min,23.1±8.3mL and 2.9±1.6 times in the chisel group and 86.6±15.1min,32.2±6.4mL and 5.6±1.0 times in the trephine group,and the intraoperative bleeding and number of fluoroscopies in the chisel group were less than those in the trephine group(P＜0.05),while no significant difference was there in the operative time between the two groups(P＞0.05).143 patients were followed up for 9-20 months.The VAS scores,JOA scores and ODI at 3d,1 month,6 months and the final follow-up of both groups showed significant improvements compared with the preoperative data,respectively(P＜0.05),and there was no statistical difference between the two groups at the same time points(P＞0.05).The intervertebral foramina area at 3d postoperatively and at the final follow-up in both groups increased than that before surgery(P＜0.05),and the rate of change in the intervertebral foramina area at 3d postoperatively and at the final follow-up in the trephine group was greater than that in the chisel group(P＜0.05).At the final follow-up,according to the MacNab standard,chisel group was excellent in 43 cases,good in 18 cases,moderate in 2 cases,and poor in 0 case,with an excellence and good rate of 96.8％,while the trephine group was excellent in 57 cases,good in 20 cases,moderate in 3 cases,and poor in 0 case,with an excellence and good rate of 96.3％.There was no statistical difference between the two groups in terms of excellent and good rate according to MacNab criteria(P＞0.05).Conclusions:The clinical efficacy of accurate foraminoplasty technique with visualized chisel is similar to foraminalplasty with trephine under FVSE,but foraminoplasty technique with visualized chisel reduces the number of fluoroscopies and bleeding volume.

Autophagy is a lysosomal dependent metabolic pathway that degrades cytoplasmic proteins and organelles via formation of autophagosomes to maintain homeostasis within the body. In recent years, with the continuous deepening of research and understanding on autophagy, it has been found that autophagy plays an important role in the occurrence of various tumor diseases and regulates autophagy could treat various tumors. Recent evidence suggests that autophagy plays a dual role in the occurrence of liver cancer: autophagy can clear damaged organelles and misfolded proteins, avoiding cell carcinogenesis; At the same time, it can also adapt malignant tumor cells to adverse environments such as chemotherapy drugs and hypoxia. This article aims to review the biological functions and molecular mechanisms of autophagy in liver cancer, and discussing the potential to modulate autophagy as a therapeutic strategy in the context of liver cancer.

Objective:To explore any effect of pulsed electromagnetic field (PEMF) stimulation on intervertebral disc degeneration (IDD).Methods:Forty Sprague-Dawley rats were randomly divided into a control group, an IDD model group, a PEMF group and an observation group. An IDD model was induced in all except those in the control group. Both the PEMF and observation groups were given PEMF stimulation, while the latter was additionally injected with the A2AR agonist CGS-21680. Eight weeks after the modelling any pathological changes in the morphology of the rats′ intervertebral disc tissues were evaluated using saffron solid green staining. The expression of A2AR, cyclic adenosine phosphate (cAMP), protein kinase A (PKA), cysteine aspartate proteolytic enzyme-3 (Caspase-3), type II collagen (COL-II) and matrix metalloproteinase-3 (MMP3) in the intervertebral discs were evaluated.Results:The nucleus pulposus had shrunk, while fibrous tissues and chondrocytes had increased in the IDD model group. In the observation group the nucleus pulposus was intact and of basically normal shape. A2AR mRNA and protein levels were higher in the intervertebral disc tissue of the model group than among the control group, on average, while the levels in the observation group were significantly higher than in the other groups. In the PEMF and observation groups cAMP and PKA mRNA were significantly higher than in the IDD model group. The p38 MAPK and P-P38 MAPK levels of the IDD model group and its average P-P38 MAPK/p38 MAPK ratio were significantly higher than in the control group. In the PEMF and observation groups those indices had decreased to varying degrees, with those of the observation group significantly lower than among the model and PEMF groups on average, except for the p38 MAPK values. Caspase-3 and its mRNA were significantly higher in the model group than in the control group, on average, and those values were significantly lower in the PEMF and observation groups than in the IDD model group. The average MMP3 contents of the IDD model group had increased significantly compared with the control group, while the Col-Ⅱ level had decreased significantly. Compared with the IDD model group, the MMP3 level had decreased but Col-Ⅱ expression had increased in both the PEMF and observation groups, with significant differences between the IDD model and observation groups.Conclusions:The activation of the p38 MAPK signaling pathway by inflammatory factors to induce apoptosis is one of the important reasons for the aggravation of IDD lesions. PEMF combined with A2AR agonists can activate the A2AR/cAMP/PKA signaling pathway, inhibit p38 MAPK phosphorylation, reduce apoptosis of nucleus pulposus cells, and relieve IDD damage.

Pentaxin 3 (PTX3), as a multifunctional glycoprotein, plays an important role in regulating inflammatory response, promoting tissue repair, inducing ectopic calcification and maintaining bone homeostasis. The effect of PTX3 on bone mineral density (BMD) may be affected by many factors. In PTX3 knockout mice and osteoporosis (OP) patients, the deletion of PTX3 will lead to decrease of BMD. In Korean community "Dong-gu study", it was found that plasma PTX3 was negatively correlated with BMD of femoral neck in male elderly patients. In terms of bone related cells, PTX3 plays an important role in maintaining the phenotype and function of osteoblasts (OB) in OP state;for osteoclast (OC), PTX3 in inflammatory state could stimulate nuclear factor κ receptor activator of nuclear factor-κB ligand (RANKL) production and its combination with TNF-stimulated gene 6(TSG-6) could improve activity of osteoclasts and promote bone resorption;for mesenchymal stem cells (MSCs), PTX3 could promote osteogenic differentiation of MSCs through PI3K/Akt signaling pathway. In recent years, the role of PTX3 as a new bone metabolism regulator in OP and fracture healing has been gradually concerned by scholars. In OP patients, PTX3 regulates bone mass mainly by promoting bone regeneration. In the process of fracture healing, PTX3 promotes fracture healing by coordinating bone regeneration and bone resorption to maintain bone homeostasis. In view of the above biological characteristics, PTX3 is expected to become a new target for the diagnosis and treatment of OP and other age-related bone diseases and fracture healing.
Animals ; Male ; Mice ; Bone Resorption/metabolism* ; Cell Differentiation ; Fracture Healing/genetics* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Osteoporosis/genetics* ; Phosphatidylinositol 3-Kinases/pharmacology*

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Animals ; Rabbits ; Atrial Fibrillation/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; NF-E2-Related Factor 2/pharmacology* ; Molecular Docking Simulation ; Oxidative Stress ; Energy Metabolism ; Mitochondria/metabolism* ; Inflammation/metabolism* ; Heme Oxygenase-1

Parkinson's disease(PD)is a chronic neurodegenerative disease and commonly seen in middle-aged and elderly people.Combined with age-related loss of bone mass, inadequate intake of vitamin D and calcium due to dysphagia and reduced gastrointestinal motility in the late stages of the disease makes PD patients more susceptible to osteoporosis(OP). Some drugs used to treat PD can also induce and even aggravate osteoporosis in PD patients.Moreover, osteoporosis further impairs mobility in PD patients, causing pain and even fractures.This article reviews the risk factors, pathogenesis, prevention and treatment of PD combined with osteoporosis.

To assess the correlation between thyroid function and glucolipid metabolism in type 1 diabetic adults. A retrospective analysis was conducted in 230 type 1 diabetic adults who were hospitalized in the Department of Endocrinology of Shandong Provincial Hospital Affiliated to Shandong University from January 2008 to January 2020. It showed that thyroid stimulating hormone(TSH) was significantly positively correlated with total cholesterol (TC) ( r=0.239), triglycerides (TG) ( r=0.166) and low-density lipoprotein cholesterol (LDL-C) ( r=0.249), respectively (all P<0.05). Free triiodothyronine (FT 3) was significantly negatively correlated with fasting plasma glucose (FPG) ( r=-0.272), glycated hemoglobin (HbA1c) ( r=-0.240), TC ( r=-0.197) and LDL-C ( r=-0.220), respectively (all P<0.05). Free thyroxine (FT 4) was negatively correlated with TC ( r=-0.171) and LDL-C ( r=-0.170), respectively (all P<0.05). TC was an independent predictor of TSH, FT 3 and FT 4, FT 3 and FT 4 were independent predictors of HbA1c. TSH was an independent predictor of TC, TG and LDL-C. Thyroid function is closely related to glucolipid metabolism in type 1 diabetic adults.