BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

Objective: To enhance the ability of nanoparticles to target and bind tumor cells by constructing a neutrophil hitchhiking system based on hyaluronic acid (HA)-modified dual-drug loaded lipid nanoparticles. Methods: Lipid nanoparticles (LNPs) were prepared using microfluidic technology, and the nitrogen/phosphate (N/P) ratio, flow rate ratio, and drug-to-lipid ratio were optimized. HA-modified LNPs (HA-LNPs) were prepared and characterized. The interaction between the nanoparticles and tumor cells was evaluated through in vitro cell experiments. Results: The optimal preparation conditions for LNPs are N/P=8, flow rate ratio=5, and drug-to-lipid ratio=1∶30 (w∶w). HA-LNPs has a particle size of (177.28±2.41) nm, a polydispersity index (PDI) of 0.198±0.10, and an siRNA encapsulation efficiency of (91.37±0.47)%. The optimal binding rate with neutrophils was (98.64±2.34)%. Conclusion: An HA-modified dual-drug loaded lipid nanoparticle-neutrophil hitchhiking system was successfully constructed, enhancing the synergistic anti-tumor activity of the nanomedicine and the uptake of nanoparticles by tumor cells, providing a novel delivery strategy for targeted therapy of bone marrow tumors.

Non-suicidal self-injury(NSSI)refers to a mental disorder characterized by deliberate self-harm behaviors without suicidal intent.The pathogenesis of NSSI remains unclear,but may be related to abnormalities in reward circuitry,pain processing,emotion regulation,impulse control and hypothalamic-pituitary-adrenal axis.Task state functional MRI(fMRI)provides valuable insights into the intrinsic connections and neural circuits mechanisms underlying NSSI during various task states or behaviors.Research progresses of task state fMRI in pathogenesis of NSSI were reviewed in this article.

Intracranial atherosclerosis(ICAS)related acute large vessel occlusion(LVO)is an important cause of ischemic stroke,posing a serious threat to public health.Recent studies have shown that there are significant differences in the incidence of ICAS-LVO between Eastern and Western populations,which will directly affect the formulation and implementation of clinical diagnosis and treatment strategies.With the rapid development of neurointerventional techniques,the clinical management model of ICAS-LVO is undergoing profound changes.A series of new techniques and concepts have been emerging from early identification to endovascular treatment,bringing new hope for improving the prognosis of ICAS-LVO patients.This article discussed the identification of clinical and imaging features of ICAS-LVO,the optimization of endovascular treatment strategies,and the application of cutting-edge technologies,and look forward to the development direction of personalized,precise diagnosis and treatment in the future,aiming to provide new ideas and methods for clinical practice of ICAS-LVO.

Objective To analyze the effects of intravenous tirofiban following endovascular treatment on the prognosis of patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization.Methods This retrospective study included consecutive patients with acute anterior circulation ischemic stroke who underwent endovascular treatment but did not achieve successful recanalization.These patients were retrospectively enrolled from the Department of Neurology at Nanjing Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,the Second Affiliated Hospital of Soochow University,Wuhan No.1 Hospital,and Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College)between January 2015 and April 2023.Baseline and clinical data were collected including age,sex,medical history(hypertension,diabetes,atrial fibrillation,hyperlipidemia),personal history(smoking and drinking),National Institutes of Health stroke scale(NIHSS)score at admission,trial of Org 10172 in acute stroke treatment(TOAST)classification(large artery atherosclerosis,cardioembolism,or other types),Alberta stroke program early CT score(ASPECTS)on admission,intravenous thrombolysis,onset-to-puncture time(OTP),collateral circulation status(poor collaterals:American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]score 0-2;good collateral:ASTIN/SIR score 3-4),procedure duration(from femoral or radial artery puncture to device removal),occlusion site,number of passes for thrombus retrieval,and post-procedural modified thrombolysis in cerebral infarction(mTICI)grade.Patients were divided into a tirofiban group and a non-tirofiban group based on whether they received post-procedural intravenous tirofiban.The primary outcome is a favorable functional outcome at 90-day since onset(modified Rankin scale[mRS]score ≤ 3).Safety outcomes included mortality at 90-day since onset(mRS score 6),any intracranial hemorrhage within 24 h post-procedure,and symptomatic intracranial hemorrhage within 24 h post-procedure.1∶1 propensity score matchings using the nearest neighbor method was performed based on variables with P＜0.05 in the comparison between the tirofiban and non-tirofiban groups.Differences in primary and safety outcomes between the matched groups were compared.Univariate and multivariate Logistic regression analyses were conducted with favorable outcomes at 90 days as the dependent variable to evaluate the effect of intravenous tirofiban administration after endovascular therapy on 90-day prognosis in patients without successful recanalization.Results A total of 356 patients without successful recanalization after endovascular treatment were included,comprising 195 males and 161 females,with a median age of 70(61,78)years(32-92 years).Among them,76 and 280patients were assigned to the tirofiban and non-tirofiban groups,respectively.At 90 days,114 patients had favorable outcomes,while 242 had unfavorable outcomes.(1)Before the 1∶1 propensity score matching,significant differences were observed between the tirofiban and non-tirofiban groups in terms of admission NIHSS score,ASPECTS,good collateral circulation,intravenous thrombolysis,and mTICI grade(all P＜0.05).After 1∶1 propensity score matching,66 matched pairs(132 patients)were obtained.No significant differences in the baseline and clinical characteristics were found between the two groups after matching(all P＞0.05).(2)After 1∶1 matching,a significant difference was observed in the rate of favorable outcomes at 90 days between the two groups(48.5％[32/66]vs.30.3％[20/66],P=0.033)after propensity score matching,while no significant differences were found in 90-day mortality,intracranial hemorrhage within 24h,or symptomatic intracranial hemorrhage within 24h(all P＞0.05).(3)Univariate analysis after 1∶1 matching indicated that age,atrial fibrillation,smoking history,admission NIHSS score,M2 segment middle cerebral artery occlusion,good collateral circulation,number of passes for thrombus retrieval,and tirofiban treatment were factors influencing favorable outcomes at 90 days.Multivariate Logistic regression analysis showed that younger age(aOR,0.942,95％CI 0.906-0.978,P=0.002),lower admission NIHSS score(aOR,0.855,95％CI 0.777-0.941,P=0.001),good collateral circulation(aOR,5.534,95％CI 2.141-14.301,P＜0.01),tirofiban treatment(aOR,2.774,95％CI 1.092-7.046,P=0.032),and M2 segment MCA occlusion(reference:internal carotid artery occlusion;aOR,4.874,95％CI 1.428-16.632,P=0.011)were independent predictors of favorable outcomes at 90 days.Conclusions Intravenous tirofiban administration after endovascular therapy may improve 90-day neurological outcomes in patients with acute anterior circulation large vessel occlusion stroke who did not achieve successful recanalization without increasing the risk of hemorrhage.Further large-scale randomized controlled trials are warranted to validate these findings.

Objective To quantitatively assess the correlation between the skeletal muscle index(SMI)of patients and the occur-rence of anastomotic leakage(AL)in rectal cancer patients after surgery,and to analyze the risk factors for AL in rectal cancer patients and the influencing factors of sarcopenia.Methods The clinical,pathological,and related imaging data of 362 patients who under-went radical surgery for rectal cancer were retrospectively analyzed.All patients underwent pelvic MRI and abdominal CT scans(plain/enhanced)within one month before surgery,and the third lumbar vertebra skeletal muscle area(L3-SMA)was measured from the images.All patients were divided into AL group(56 cases)and control group(306 cases)based on the presence or absence of postoperative complications.The differences in clinical characteristics and imaging parameters between the two groups were analyzed.A logistic risk prediction model was established.Results Significant differences were observed between the two groups in sarcopenia,type of surgery,surgical approach,serum albumin level,operation duration,stoma type,and extramural vascular invasion(EMVI)(P＜0.05).These factors were incorporated in a multivariate logistic regression analysis model,the area under the curve(AUC)of receiver operating characteristic(ROC)curve of the model was 0.810[95％confidence interval(CI)0.743-0.876,P＜0.001],with a sensitivity of 0.865 and specificity of 0.669.Conclusion Sar-copenia is a significant risk factor for AL after rectal cancer surgery.It enhances the predictive efficacy for postoperative AL and serves as a basis for identifying high-risk populations for AL in clinical practice.

Objective The aim of this study was to explore the mechanism of Naotaifang(NFT)in preventing neuronal pyroptosis in cerebral ischemia-reperfusion injury(CIRI).Methods Firstly,a network Meta-analysis was conducted to compare the clinical efficacy of Naotaifang and dl-3-n-butylphthalide in treating ischemic stroke,and dl-3-n-butylphthalide was identified as the positive control drug in this study.Then,a rat CIRI model was established using the middle cerebral artery occlusion/reperfusion(MCAO/R)method.Sixty adult male SD rats were randomly divided into model group(Model group),low-dose Naotaifang group(NTF-L group),medium-dose Naotaifang group(NTF-M group),ahigh-dose Naotaifang group(NTF-H group),NBP group(NBP group),and a sham surgery group(Sham group)using a random number table method,with 10 rats in each group.After MCAO/R,rats received NTF(4.5 g/kg for NTF-L,9 g/kg for NTF-M,and 18 g/kg for NTF-H)or Nimodipine(60 mg/kg)or distilled water(Sham group and Model group)via gavage for seven consecutive days.Neurological function was evaluated using the Zea Longa method,infarct volume was assessed by TTC staining,and HE and Nissl staining were used to observe changes in neurons in the ischemic cortex.ELISA was used to measure serum IL-1β and IL-18 levels,and Western blot was used to detect caspase-1 and GSDMD expression in the ischemic cortex.Results Network Meta-analysis showed no significant difference in clinical efficacy,neurological function scores,and TXB2 expression between Nimodipine and NTF interventions.Animal experiments revealed that neurological scores of the Model group was significantly increased,the volume of cerebral infarction was significantly enlarged,the structure of nerve cells in the ischemic cortical area was destroyed,and the number of nerve cells and Nissl bodies was significantly reduced,and expressions of IL-1β,IL-18 inflammatory factors and caspase-1,and GSDMD focal proteins were significantly decreased(P<0.01).The NTF-H group significantly reduced neurological function scores and cerebral infarction volume of rats in the Model group,significantly improved morphology of nerve cells and the number of Nissl body,and significantly decreased the expressions of IL-1β,IL-18 inflammatory factors,caspase-1,and GSDMD necroptosis proteins(P<0.01).There was no significant difference between the NTF-H group and the NBP group in terms of neurological scores,volume of cerebral infarction,IL-1β,IL-18 levels,and caspase-1 and GSDMD protein expression(P>0.05).Conclusion Both NTF and Nimodipine have therapeutic effects on ischemic stroke patients,with no significant difference between them,making Nimodipine a suitable positive control drug.NTF may alleviate CIRI by reducing pyroptosis through the caspase-1/GSDMD signaling pathway.

The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."

BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.