BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

Objective: To explore the key factors affecting the selection and effectiveness of bladder management modalities in patients with spinal cord injury，so as to provide reference for the optimization of individualized bladder management strategies. Methods: The clinical and follow-up data of 78 patients with spinal cord injury treated in our hospital during Jan.1,2013 and Dec.31,2022 were retrospectively analyzed.The distribution of bladder management modalities among different grades of injuries was analyzed. Bowker symmetry test was used to evaluate the difference between bladder management modalities at discharge and at the end of follow-up. Multiple linear regression was used to explore the influencing factors of bladder management effects. Plotting Kaplan-Meier survival curves were adopted to calculate the median time of changes in bladder management. Results: At discharge，there were 9 cases of self-catheterization，19 cases of intermittent catheterization，22 cases of reflexive voiding，26 cases of long-term catheterization，and 2 cases using urinary collector.At the end of follow-up，there were 15 cases of self-catheterization，8 cases of intermittent catheterization，34 cases of reflexive voiding，14 cases of long-term catheterization，and 7 cases using urinary collector.There was a significant difference between the modalities of bladder management at discharge and at the end of follow-up (χ =21.43，P=0.018).Multiple linear regression showed a significant decrease of 8.60 in the total neurogenic bladder symptom score (NBSS) for grade D injuries compared with grade A injuries (P=0.026). The median time to bladder management change was 7.93 months (95%CI:5.44-9.44), with approximately 50% of patients experiencing a change in bladder management within 8 months after discharge. Conclusion: The modalities of bladder management changed significantly after discharge.The grade of injury was a key factor affecting the effectiveness of bladder management.Higher grade was associated with worse effectiveness of bladder management.

Objective: Previous observational studies have confirmed the correlation between gut microbiota and bladder cancer，but the causal relationship is still unclear.This study aimed to explore the causal relationship between them with Mendelian randomization. Methods: Genetic variation summary data of 211 gut microbiota and bladder cancer genome-wide association studies (GWAS) were obtained from the MiBioGen Consortium and Finngen database.Single nucleotide polymorphisms (SNPs) closely related to these studies were screened as instrumental variables.The causal relationship between gut microbiota and bladder cancer were analyzed with inverse variance weighting (IVW)，MR-Egger，weighted median，maximum likelihood，robust adjustment feature score and MR-PRESSO，with IVW as the primary analysis method.Additionally，sensitivity analysis was used to test the heterogeneity (Cochran Q) and horizontal pleiotropy (MR-Egger intercept term and global test from MR-PRESSO estimator) to ensure the robustness of the results. Results: The IVW results indicated that Lachnospiraceae UCG004 (OR：1.42)，Desulfovibrionales (Order) (OR：1.48)，Eubacterium ruminantium group (OR：1.33)，Olsenella (OR：1.24)，Ruminococcaceae UCG002 (OR：1.39)，Ruminococcaceae UCG005 (OR：1.42) and Ruminococcaceae UCG013 (OR：1.64) significantly increased the risk of bladder cancer.Conversely，Bacteroidetes (Phylum) (OR：0.61)，Eubacterium brachy group (OR：0.80)，Ruminococcaceae UCG004 (OR：0.73)，Rikenellaceae (Family) (OR：0.67)，Lachnospiraceae ND3007 group (OR：0.47), Adlercreutzia (OR：0.73) and an unknow genus (OR：0.75) were associated with a reduced risk of bladder cancer.Sensitivity analyses did not reveal any heterogeneity or horizontal pleiotropy. Conclusion: This study reveals the causal role of 14 gut microbiota in the pathogenesis of bladder cancer，among which Lachnospiraceae UCG004，Desulfovibrionales (Order)，Eubacterium ruminantium group，Olsenella，Ruminococcaceae UCG002，Ruminococcaceae UCG005 and Ruminococcaceae UCG013 are risk factors for bladder cancer，while Bacteroidetes (Phylum)，Eubacterium brachy group，Ruminococcaceae UCG004，Rikenellaceae (Family)，Lachnospiraceae ND3007 group，Adlercreutzia and an unknown genus are the protective factors.

Objective: To compare the effects of high intensity interval training (HIIT) exercise prescription based on machine vision and routine on HIIT the physical and mental health of female college students with simple obesity, so as to provide a basis for the development of weight loss intervention plans for this population. Methods: From August 2023 to February 2024, 115 female college students with simple obesity, selected from Lianyungang Vocational and Technical College and East China Normal University, were randomly divided into a control group ( n =57) and an observation group ( n =58) according to a random number table. The control group received routine HIIT, while the observation group received machine vision based on HIIT exercise prescription (including image acquisition module, image processing module, database management module, backend computer processing and feedback, intelligent evaluation module, which could be customized according to the subjects preferences, providing exercise prescription based on the selected training program and supervised its standardized completion of the training plan). Both were intervened for 12 weeks, 30 minutes each time, once every 2 days, and rest every Sunday. The t-test was used to compare body shape, glucose and lipid metabolism, cardiopulmonary function indicators, anxiety and depression states between two groups before and after intervention. Results: Before intervention, there were no statistically significant differences in physical and mental health status indicators between two groups of female college students ( t =0.13-0.86, all P >0.05). After intervention, body mass indexes, waist hip ratios, body fat percentage, fasting plasma glucose, 2hour postprandial plasma glucose, hemoglobin A1c, triglycerides, total cholesterol, lowdensity lipoprotein cholesterol (LDL-C), anxiety and depression scores were all reduced in both groups ( t-observation =-6.94 to -12.92, t-control =-2.71 to -10.95 ), of which the observation group [(23.46±2.18)kg/m 2, 0.70±0.06, (28.03±3.16)%, (4.55±0.67)mmol/L, (6.03±0.74)mmol/L, (5.10±0.70)%, (1.63±0.31)mmol/L, (4.24±0.58)mmol/L, (2.45±0.43)mmol/L, 35.28±4.76, and 33.03±4.03] were lower compared with the control group [(26.54±2.32)kg/m 2, 0.77±0.06, (30.74±4.38)%, (5.03±0.76)mmol/L, (6.62±0.82)mmol/L, (5.82±0.73)%, (1.98±0.35)mmol/L, (4.95±0.61)mmol/L, (2.88±0.47)mmol/L, 39.18±5.04, and 37.25±4.16] ( t =-7.34, -6.26 , -3.81, -3.59, -4.05, -5.40, -5.68, -6.40, -5.12, -4.27, -5.53)(all P <0.05). After intervention, high density lipoprotein cholesterol, stroke volume, left ventricular ejection fraction, maximum oxygen consumption, volume of tidal, and vital capacity increased in both groups ( t-observation =7.43-18.23, t-control =3.89-10.13), of which the observation group [(1.49±0.22)mmol/L, ( 72.35± 4.69)mL, (68.95±5.10)%, (36.97±3.22)mL/(kg ·( min), (25.29±4.11)mL/(kg · ( min), and (3 374.26±169.54)mL] were higher compared with the control group [(1.23±0.20)mmol/L, (67.32±4.06)mL, (64.83±5.05)%, (33.24±3.14)mL/(kg · ( min), (23.01± 3.58 )mL/(kg · ( min), and (3 197.50±125.81)mL] ( t =6.63, 6.15, 4.35, 6.29, 3.17, 6.34)(all P <0.05). Conclusion HIIT exercise prescription based on machine vision has better effects than routine HIIT on impoving the body shape, glucose and lipid metabolism, cardiopulmonary function of female college students with simple obesity, and also their mental health.

Background::Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods::GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice ( Grk2?SM22), and littermate controls ( Grk2flox/flox) were grouped into control and hypoxia mice ( n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results::The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2?SM22 mice compared with littermate controls. The amelioration of PH in Grk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion::Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

Objective To compare the effects of different dose prediction models of sufentanil in elderly hip arthroplasty with ultrasound-guided bow tie fascia iliac block.Methods A total of 90 elderly patients who underwent ultrasound-guided bow tie fascia iliac during hip arthroplasty in our hospital from June 2018 to June 2022 were selected.The dose of sufentanil was determined by a linear regression(ALR),multiple linear regression(MLR)or deep belief networks(DBN).Patients were randomly divided into the ALR group,the MLR group and the DBN group,with 30 cases in each group.The analgesic effect,hemodynamic index,inflammatory factor level and surgical index were compared among all groups.Kaplan-Meier method was used to analyze the incidence of hip infection 2 weeks after surgery in each group.Results There was no significant difference in the gender,age,body weight,American Society of Anesthesiologists(ASA)classification or complications among all groups(P>0.05).The Harris score 24 hours after surgery and duration of sensory block in the DBN group were higher/longer than those in the ALR group,numerical rating scale(NRS)score 24 hours after surgery,mean arterial pressure(MAP)and heart rate(HR)at the beginning of surgery and 30 minutes after surgery,levels of interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)24 hours after surgery,onset time of sensory block,and number of patient controlled analgesia(PCA)compression were lower/earlier/less than those in the ALR group,the modified observer's assessment of alertness/sedation scale(OAA/S)score 24 hours after surgery was significantly lower than those in the ALR group and the MLR group,with statistically significant differences(P<0.05).Harris score 24 hours after surgery and duration of sensory block in the MLR group were higher/longer than those in the ALR group,modified OAA/S score 12 hours after surgery,MAP 30 minutes after surgery,levels of IL-17 and TNF-α 24 hours after surgery,onset time of sensory block,and the number of PCA compressions were lower/longer/less than those in the ALR group,with statistically significant differences(P<0.05).Kaplan-Meier analysis showed that there were significant differences in the incidences of hip infection 2 weeks after surgery among all groups(P<0.05),and there were significant differences in the incidences of hip infection 2 weeks after surgery between the ALR group and the DBN group(P<0.05).Conclusion The effectiveness of calculating the dose of sufentanil using the MLR and DBN in elderly hip arthroplasty with bow tie fascia iliac block is better than that of ALR,and the advantage of DBN is more obvious.

Objective To investigate the factors influencing prognosis in patients with acute myocardial infarction complicated with cardiogenic shock undergoing primary percutaneous coronary intervention(PPCI).Methods Patients with acute myocardial infarction complicated with cardiogenic shock who underwent PPCI at our hospital between January 2015 and December 2019 were enrolled.Clinical baseline characteristics,coronary angiography and PCI-related parameters,and mechanical support information were collected.The patients were followed up for one year and divided into survival and death groups based on their survival status within one year.Differences in various factors between the two groups were compared.Results A total of 40 patients were enrolled,including 26 in the survival group and 14 in the death group.There were no differences in baseline data,diagnosis,risk factors,and comorbidities between the two groups.The survival group had a lower heart rate and higher blood pressure trend at admission compared to the death group.Myocardial enzymes were significantly lower in the survival group compared to the death group(median CK peak:496.00(198.25,2 830.00)U/L vs.3 040.00(405.75,5 626.53)U/L,P=0.003;median CK-MB peak:52.65(31.75,219.50)U/L vs.306.00(27.25,489.63)U/L,P=0.006).When comparing coronary angiography and PCI-related indicators between the two groups,the survival group had a higher rate of complete revascularization compared to the control group(53.85％vs.21.43％,P=0.048).The survival group had a higher proportion of extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)support compared to the control group[38.46％vs.7.14％,P=0.034].Conclusions Survival in patients with acute myocardial infarction complicated with cardiogenic shock undergoing PPCI is associated with lower level of myocardial enzymes,ECMO combined with IABP support and complete revascularization.

Objective:To investigate the effect of microgravity-mediated Notch1 signaling on macrophage polarization on bone homeostasis.Methods:The animal model was constructed by tail-limb suspension(HLS)to simulate the microgravity environment.The animals were grouped into Control group,HLS group,HLS+NC group,HLS+si group,HLS+rhNF-κB group.ELISA was used to detect the content of TNF-α and IL-1β in serum of rats.TUNEL staining was used to detect the apoptosis of bone tissue.Immunofluo-rescence was used to detect the polarization of macrophages in bone tissue.The rat osteoblast CP-R091 microgravity model was con-structed by simulating the microgravity environment with a rotating wall bioreactor.The cell experiments were divided into Control group,HLS group,HLS+NC group,HLS+si group,HLS+rhNF-κB group.CCK-8 test was used to detect the proliferation activity of cells in each group,and AO test was used to test the apoptosis rate of cells in each group.PCR was used to detect the expression of os-teogenesis-related genes in bone tissues and cells.Western blot was used to detect the expression of Notch1,hair division-related en-hancer-1(HES-1),and Notch pathway ligand 1(Jagged1)in bone tissues and cells of each group.Results:Compared with control group,the contents of TNF-α and IL-1β in the serum of the rats in the HLS group,the apoptosis rate,and the proportion of M1 macro-phages were significantly increased.Compared with HLS group,the HLS+si group could obviously partially reverse the change trend of the above parameters,while HLS+rhNF-κB group significantly changed the above parameter values.Compared with control group,the proliferation activity of the cells in the HLS group was significantly reduced,and the apoptosis rate was significantly increased.Com-pared with HLS group,the HLS+si group could obviously partially reverse the change trend of the above parameters,while the HLS+rhNF-κB group made the above parameter values worse.The expressions of the osteogenesis-related genes collagen type Ⅰ(COL1),osteocalcin(OCN)and Runt-related transcription factor 2(RUNX2)in bone tissues and cells in the microgravity environment were significantly decreased,while the expressions of Notch-1,Hes-1 and Jagged1 were significantly increased,and the differences were statistically significant(all P<0.05).Conclusion:Microgravity-mediated Notch1 signaling regulates M1/M2 polarization of macro-phages,participates in cell proliferation and apoptosis in bone tissue,and affects the progress of bone homeostasis.