Objective: To explore new therapeutic strategies for periodontitis, this study prepared extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) loaded with saikosaponin D (SSD) and evaluated their efficacy in a mouse model of periodontitis. Methods: This study was approved by the Medical Ethics Committee and the Laboratory Animal Ethics Committee of the unit. hUC-MSCs at logarithmic growth phase were seeded into 96 well plates and then treated with various concentrations of SSD for 24 hours. The CCK-8 assay was used to determine the SSD concentration that preserves hUC-MSC viability. Flow cytometry (FCM) assessed SSD-induced apoptosis in hUC-MSCs and determined drug loading and loading efficiency. Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) characterized the morphology and size of hUC-MSCs-EVs and hUC-MSCs-SSD-EVs. C57BL/6J mice were divided into five groups with six mice per group: control group, periodontitis model group (PD), PD+SSD group (2 mg/kg), PD+hUC-MSCs-EVs group (10 μg/μL) and PD+hUC-MSCs-SSD-EVs group (10 μg/μL). Administration was performed 3 times a week for 4 consecutive weeks. Micro-CT and hematoxylin-eosin (HE) staining evaluated alveolar bone resorption in periodontal tissues of a mouse model of periodontitis. RT-qPCR measured inflammatory cytokine expression in periodontal tissues of a mouse model of periodontitis. Immunofluorescence analyzed macrophage M1/M2 polarization and runt-related transcription factor 2 (RUNX2) protein expression in periodontal tissues of a mouse model of periodontitis. Results: The CCK-8 assay showed that 10 μmol/L SSD had little effect on hUC-MSCs viability (P>0.05). FCM confirmed the successful loading of SSD into EVs with a loading efficiency of 11.40%. TEM and NTA revealed that hUC-MSCs-SSD-EVs presented round or oval membranous structures with diameters ranging from 200 to 300 nm. Micro CT and HE staining showed that, compared with the PD group, the distance from cementoenamel junction to alveolar bone crest (CEJ-ABC) was markedly shortened (P<0.01）.The alveolar bone of periodontitis‑model bone volume fraction (BV/TV) and trabecular number (Tb.N) were significantly elevated in the PD+hUC-MSCs-SSD-EVs group (P<0.01). RT-qPCR and IF results showed that hUC-MSCs-SSD-EVs in periodontal tissues markedly downregulated the expression of pro-inflammatory cytokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, interleukin-12 and interleukin-22 (P<0.01), upregulated the expression of the anti-inflammatory factor interleukin-10 (P<0.01), promoted the polarization of macrophages from the M1 phenotype to the M2 phenotype, and elevated the protein expression level of RUNX2 (P<0.01). Conclusion hUC-MSC-SSD-EVs effectively alleviated inflammatory responses in a mouse model of maxillary periodontitis and reduced alveolar bone loss, providing a new idea for the treatment of periodontitis.

Objective: To analyze the correlation between serum homocysteine (Hcy) and both folic acid (FA) and sperm DNA fragmentation index (DFI), so as to provide the evidence for male fertility assessment. Methods: Males who visited and measured the serum Hcy in the Reproductive Medicine Center of Huzhou Maternal and Child Health Care Hospital from September 2022 to September 2023 were selected as the study subjects. Sperm quality parameters and sperm DFI were analyzed by collecting sperm. Hcy and FA were measured by collecting venous blood. Participants were stratified into a high Hcy group (Hcy≥15.0 μmol/L) and a normal group (Hcy<15.0 μmol/L). The correlations between serum Hcy and FA and sperm DFI were evaluated using linear regression models. Results: A total of 173 participants were enrolled, including 39 in the high Hcy group and 134 in the normal group. The sperm concentration in the high Hcy group was significantly lower than that in the normal group [(91.77±61.11)×106/mL vs. (144.21±106.82)×106/mL, P<0.05]. No statistically significant differences were observed in semen volume, sperm motility, curvilinear velocity, straight-line velocity, average path velocity, or sperm morphology normal rate (all P>0.05). The FA level in the high Hcy group was lower than that in the normal group [(4.44±1.79) nmol/L vs. (7.64±3.68) nmol/L, P<0.05]. The sperm DFI in the high Hcy group was higher than that in the normal group [(19.21±8.85)% vs. (13.07±6.43)%, P<0.05]. Serum Hcy level showed a negative correlation with FA level (r=-0.369, P<0.05) and a positive correlation with sperm DFI (r=0.351, P<0.05). Conclusion Serum Hcy level is associated with sperm concentration, FA and sperm DFI, suggesting that serum Hcy may affect sperm quality.

Objective To investigate the effects of different timing of initiation of rivaroxaban anti-coagulation therapy on the efficacy and bleeding risk of atrial fibrillation patients after stroke.Methods A total of 336 patients with atrial fibrillation and stroke admitted in our hospital be-tween January 2021 and December 2023 were consecutively enrolled,and randomly divided into an experimental group(165 cases)and a control group(171 cases).The experimental group received rivaroxaban treatment within 48 h of symptom onset,whereas the control group initiated oral ri-varoxaban treatment on the 3rd,6th,and 12th day post-stroke onset,respectively,depending on stroke severity(mild,moderate,and severe).Their baseline clinical data were collected,and all of them were followed up till 90 d after stroke.The incidences of recurrent ischemic stroke,symp-tomatic intracranial hemorrhage and extracranial hemorrhage,mortality,and proportion of pa-tients with mRS score≤ 2 and distribution of the score were observed and analyzed in the two groups.Results During a 90-day follow-up period,the patients with moderate stroke from the ex-perimental group of patients exhibited a significantly lower rate of recurrent ischemic stroke than those in the control group(5.4％vs 15.9％,P=0.037).However,for patients with mild and se-vere stroke,no obvious difference was observed in the primary endpoint of recurrent ischemic stroke between the experimental and control groups(3.0％vs 3.2％,12.5％vs 14.8％,P＞0.05).Though no statistical differences were observed,lower rates of symptomatic intracranial hemor-rhage(1.5％vs 3.2％,5.4％vs 9.8％),reduced incidence of extracranial hemorrhage(9.0％vs 14.5％,12.2％vs 15.9％),and lower mRS score[1(0,2)vs 1(1,2),3(1,4)vs 3(2,4)]were seen in the patients with mild and moderate stroke from the experimental group when compared with the control group(P＞0.05).Similarly,there were no statistically differences for the severe stroke patients between the experimental and control groups(P＞0.05)in the incidence of extracranial hemorrhage(20.8％vs 22.2％),rate of symptomatic intracranial hemorrhage(20.8％vs 7.4％),mortality(8.3％vs 3.7％),and mRS score[4(3,4)vs 3(3,4)].Two patients from the experimen-tal group died,with one case due to secondary pulmonary infection and the other due to brainstem hemorrhage.In the control group,only one death occurred due to brainstem hemorrhage.Conclu-sion For atrial fibrillation patients,anticoagulation with rivaroxaban within 48 h after stroke has no significant increase in the risk of bleeding,reduces the proportion of recurrent ischemic stroke in patients with moderate stroke,and may improve the prognosis of patients.

Objective To investigate the clinical efficacy and safety of intravenous thrombolysis with tenecteplase in the treatment of CWS.Methods A prospective study was conducted on 136 CWS patients consecutively admitted in Department of Neurology of Zhengzhou People's Hospital from March 2019 to March 2024.They were randomly divided into a tenecteplase group(67 cases)and a control group(69 cases).NIHSS was used to evaluate the recovery of neurological function after treatment.mRS was employed to assess long-term prognosis.Results Significantly larger proportion of white matter lesions and higher baseline SBP level were observed in the tenecteplase group than the control group(P＜0.05).The tenecteplase group obtained obviously greater ratio of overall recovery than the control group,with notably lower NIHSS score,incidence of new CWS attacks and proportion of new acute cerebral infarction at 24 and 72 h and 7 d after treat-ment(P＜0.05,P＜0.01).Moreover,the proportion of mRS score of 0-2 was notably greater,while that of the score of 3-6 was lower in the tenecteplase group than the Control group(P＜0.05).Intravenous thrombolysis with tenecteplase was an influencing factors for 90-day mRS score of 0-2 and of 3-6 in the CWS patients(OR=0.264,95％CI:0.089-0.813;OR=4.144,95％CI:1.184-14.506,P＜0.05).Conclusion Intravenous thrombolysis with tenecteplase for CWS significantly improves the proportion of patients with good prognosis.

Objective To investigate the clinical efficacy and safety of intravenous thrombolysis with tenecteplase in the treatment of CWS.Methods A prospective study was conducted on 136 CWS patients consecutively admitted in Department of Neurology of Zhengzhou People's Hospital from March 2019 to March 2024.They were randomly divided into a tenecteplase group(67 cases)and a control group(69 cases).NIHSS was used to evaluate the recovery of neurological function after treatment.mRS was employed to assess long-term prognosis.Results Significantly larger proportion of white matter lesions and higher baseline SBP level were observed in the tenecteplase group than the control group(P＜0.05).The tenecteplase group obtained obviously greater ratio of overall recovery than the control group,with notably lower NIHSS score,incidence of new CWS attacks and proportion of new acute cerebral infarction at 24 and 72 h and 7 d after treat-ment(P＜0.05,P＜0.01).Moreover,the proportion of mRS score of 0-2 was notably greater,while that of the score of 3-6 was lower in the tenecteplase group than the Control group(P＜0.05).Intravenous thrombolysis with tenecteplase was an influencing factors for 90-day mRS score of 0-2 and of 3-6 in the CWS patients(OR=0.264,95％CI:0.089-0.813;OR=4.144,95％CI:1.184-14.506,P＜0.05).Conclusion Intravenous thrombolysis with tenecteplase for CWS significantly improves the proportion of patients with good prognosis.

Objective To investigate the effects of different timing of initiation of rivaroxaban anti-coagulation therapy on the efficacy and bleeding risk of atrial fibrillation patients after stroke.Methods A total of 336 patients with atrial fibrillation and stroke admitted in our hospital be-tween January 2021 and December 2023 were consecutively enrolled,and randomly divided into an experimental group(165 cases)and a control group(171 cases).The experimental group received rivaroxaban treatment within 48 h of symptom onset,whereas the control group initiated oral ri-varoxaban treatment on the 3rd,6th,and 12th day post-stroke onset,respectively,depending on stroke severity(mild,moderate,and severe).Their baseline clinical data were collected,and all of them were followed up till 90 d after stroke.The incidences of recurrent ischemic stroke,symp-tomatic intracranial hemorrhage and extracranial hemorrhage,mortality,and proportion of pa-tients with mRS score≤ 2 and distribution of the score were observed and analyzed in the two groups.Results During a 90-day follow-up period,the patients with moderate stroke from the ex-perimental group of patients exhibited a significantly lower rate of recurrent ischemic stroke than those in the control group(5.4％vs 15.9％,P=0.037).However,for patients with mild and se-vere stroke,no obvious difference was observed in the primary endpoint of recurrent ischemic stroke between the experimental and control groups(3.0％vs 3.2％,12.5％vs 14.8％,P＞0.05).Though no statistical differences were observed,lower rates of symptomatic intracranial hemor-rhage(1.5％vs 3.2％,5.4％vs 9.8％),reduced incidence of extracranial hemorrhage(9.0％vs 14.5％,12.2％vs 15.9％),and lower mRS score[1(0,2)vs 1(1,2),3(1,4)vs 3(2,4)]were seen in the patients with mild and moderate stroke from the experimental group when compared with the control group(P＞0.05).Similarly,there were no statistically differences for the severe stroke patients between the experimental and control groups(P＞0.05)in the incidence of extracranial hemorrhage(20.8％vs 22.2％),rate of symptomatic intracranial hemorrhage(20.8％vs 7.4％),mortality(8.3％vs 3.7％),and mRS score[4(3,4)vs 3(3,4)].Two patients from the experimen-tal group died,with one case due to secondary pulmonary infection and the other due to brainstem hemorrhage.In the control group,only one death occurred due to brainstem hemorrhage.Conclu-sion For atrial fibrillation patients,anticoagulation with rivaroxaban within 48 h after stroke has no significant increase in the risk of bleeding,reduces the proportion of recurrent ischemic stroke in patients with moderate stroke,and may improve the prognosis of patients.

Objective·To evaluate the effects of anterior maxillary segmental distraction osteogenesis(AMSDO)in treating sagittal maxillary hypoplasia in cleft lip and palate(CLP)patients and to report a 3D-printed surgical guide to facilitate the osteotomy.Methods·Twelve patients with CLP who underwent AMSDO were included in this study.Virtual osteotomy was performed in a 3-dimensional model and the osteotomy line were fabricated into a tooth-borne surgical guide by using 3D-printing technique.Lateral cephalograms taken before surgery(T0),at the end of consolidation(T1)and six months after consolidation(T2)were used to evaluate the effects of AMSDO.The accuracy of the osteotomy guide was measured by superimposing the postoperative CT data to virtual planning.Results·All the patients went through surgery without serious complications.SNA and overjet changed significantly both from T0 to T1 and from T0 to T2.ANB,facial convexity,and palatal length changed without significance from T0 to T1 and from T0 to T2.SNB remained stable.All the variables remained relatively stable from T1 to T2.The anteroposterior linear root-mean-square deviation(RMSD)between planning and actual results was 0.90 mm,while the angular RMSD in the sagittal plane was 5.07°.Conclusion·AMSDO is an effective treatment for maxillary hypoplasia secondary to CLP.The accuracy of this 3D-printed osteotomy guide is clinically acceptable,and this can simplify the surgery with fewer complications.

Objective To investigate the factors affecting the prognosis of endovascular treatment(EVT)for acute vertebrobasilar artery occlusion(AVBAO)within 24 h of onset of disease.Methods General and clinical data of AVBAO patients admitted to the Department of Cerebrovascular Diseases,Henan Provincial People's Hospital who received EVT within 24h of onset from October 2020 to September 2023 were retrospectively and consecutively included,including age,sex,stroke-related risk factors(hyperlipidemia,hypertension,diabetes mellitus,atrial fibrillation,coronary artery disease,smoking,and previous stroke),preoperative National Institutes of Health stroke scale(NIHSS)score,preoperative modified Rankin scale(mRS)score,form of onset,preoperative intravenous thrombolysis,posterior circulation Alberta stroke program early CT score(pc-ASPECTS),basilar artery on computed tomography angiography(BATMAN)score,site of occlusion(intracranial segment of vertebral artery,basilar artery),and surgical procedure(direct aspiration and/or stent-retrieval,balloon dilatation,stenting,etc.First-line stenting or balloon dilatation is direct angioplasty;if blood flow cannot be maintained after thrombectomy,further balloon dilatation and/or stenting is required as remedial angioplasty),onset-to-puncture time,puncture-to-recanalization time,and postprocedure immediate modified thrombolysis in cerebral infarction(mTICI)grading(successful recanalization was defined as mTICI grading 2b or 3),and perioperative complications(intraprocedural thrombus migration,intraprocedural reocclusion,intraprocedural dissection,postoperative hemorrhagic transformation within 3 d,and symptomatic intracranial hemorrhage[sICH]).Patient prognosis was assessed by mRS score at 90 d postoperatively.The mRS score≤3 was classified as good prognosis,and mRS score＞3 was classified as poor prognosis.Indicators with P＜0.1 in the results of univariate analysis were included,and variables were screened by backward elimination and subjected to multifactorial Logistic regression analysis to analyze the factors influencing the prognosis of AVBAO patients undergoing EVT within 24 h of the onset of the disease.Results A total of 149 AVBAO patients who underwent EVT were included,including 79 patients with good prognosis,70 patients with poor prognosis,145 patients with successful revascularization,34 patients with perioperative complications,and 32 patients with death.(1)The results of univariate analysis showed that compared with patients with poor prognosis,patients with good prognosis had lower preoperative NIHSS scores(16.0[12.0,23.0]vs.24.5[16.8,31.3],Z=-4.280,P＜0.01)and preoperative mRS scores(4[4,4]vs.5[4,5],Z=-4.711,P＜0.01),a lower percentage of diabetes mellitus(15.2％[12/79]vs.35.7％[25/70],x2=8.376,P=0.004),and the incidence of postoperative hemorrhagic transformation within 3d(7.6％[6/79]vs.25.7％[18/70],x2=-0.246,P=0.003)and the incidence of sICH(1.3％[1/79]vs.14.3％[10/70],x2=-0.249,P=0.002)were significantly lower in patients with good prognosis than that in patients with poor prognosis.(2)Age,hyperlipidemia,diabetes mellitus,preoperative NIHSS score,preoperative mRS score,postoperative hemorrhagic transformation within 3 d and sICH were included in multifactorial Logistic regression analysis,which showed that hyperlipidemia(OR,2.433,95％CI 1.088-5.441),diabetes mellitus(OR,2.797,95％CI 1.168-6.701),high preoperative NIHSS score(OR,3.715,95％CI 1.684-8.195),and postoperative sICH within 3 d(OR,19.681,95％CI 1.984-195.192)were the independent risk factors for poor prognosis of patients with AVBAO who underwent EVT within 24 h of onset(all P＜0.05).Conclusion Hyperlipidemia,diabetes mellitus,high preoperative NIHSS score,and postoperative sICH within 3 d were independent risk factors for poor prognosis in AVBAO patients who underwent EVT within 24 h of onset.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.