In the tumor microenvironment, a bidirectional feedback regulation exists between aberrant angiogenesis and antitumor immunity, which provides a basis for the synergistic effects of antiangiogenic therapy and immunotherapy. The underlying mechanisms include relief of immunosuppression mediated by proangiogenic factors, induction of vascular normalization to reshape the immune microenvironment, and formation of a positive immune-vascular feedback loop. Based on these mechanisms, the combination of antiangiogenic therapy and immunotherapy has demonstrated synergistic efficacy in advanced non-small cell lung cancer (NSCLC) and is gradually being moved forward to the neoadjuvant setting. However, in the perioperative treatment of resectable lung cancer, this regimen still faces challenges, including primary resistance, a brief window of vascular normalization, and an unclear understanding of spatial interaction mechanisms. This review systematically elucidates the synergistic mechanisms of antiangiogenic agents combined with immunotherapy in NSCLC and the latest advances of this combination strategy in the neoadjuvant therapy setting, aiming to provide a reference for clinical practice.

Objective To evaluate the safety and efficacy of the Neuroform EZ self expanding stent for severe symptomatic intracranial atherosclerotic stenosis(sICAS).Methods Retrospectively enrolled consecutive patients with severe sICAS who underwent percutaneous transluminal angioplasty and stenting(PTAS)with a Neuroform EZ stent in the Department of Cerebrovascular Disease,Henan Provincial People's Hospital,from March 2020 to December 2022.Baseline demographic and clinical data were collected,including age,sex,hypertension,diabetes mellitus,coronary artery disease,dyslipidemia,hyperhomocysteinemia,transient ischemic attack(TIA)and ischemic stroke,smoking history,modified Rankin scale(mRS)score at admission,and National Institutes of Health stroke scale(NIHSS)score.Preoperative imaging data included target vessel(basilar artery,intracranial segment of the internal carotid artery,middle cerebral artery,and intracranial vertebral artery),lesion length,degree of stenosis,and vascular morphology according to the Mori classification(type A,lesion length＜5 mm with concentric or moderately eccentric stenosis;type B,lesion length＜10 mm with severely eccentric stenosis;type C,lesion length＞10 mm or arterial angulation＞90°).Technical success was defined as accurate delivery and deployment of the stent with complete coverage of the target lesion and immediate post deployment residual stenosis＜50%.Postoperative head CT was performed to detect intracranial hemorrhage.Periprocedural complications were recorded,including intracranial hemorrhage,arterial dissection,in stent thrombosis,and perforator occlusion occurring intraoperatively within 72 hours after the procedure.At one-month post-operation,patients were seen through outpatient follow-up for TIA,hemorrhagic or ischemic stroke,and all cause death.At 6 months after surgery,DSA or CT angiography(CTA)was performed to assess in stent restenosis(ISR,defined as＞50%stenosis within the stent or within5mm of its edges,or＞20%luminal loss).At 1 and 2 years postoperatively,ipsilateral ischemic stroke or TIA recurrence was assessed by outpatient visit or telephone follow up.Results A total of 76 patients with severe sICAS underwent PTAS with a Neuroform EZ stent(56 males,20 females,age 47-80 years,with a mean age of[61±10]years).(1)Within all patients enrolled,40 had middle cerebral artery,16 with basilar artery,6 with intracranial vertebral artery and 14 with intracranial internal carotid artery.The preprocedural lesion length was 2-15 mm,with a mean length of(6.2±2.5)mm,and stenosis severity was70%-99%,the mean severity was(83.2±6.9)%,with Mori type B being the most common type(57.9%[44/76]).(2)PTAS was successfully completed on all patients(technical success 100%).Pre dilation with a conventional balloon was performed in all cases(using balloon with diameter of 1.5-3.5mm,and stent with diameter of 2.5-4.5 mm and length of 15-30 mm).Immediate post procedural residual stenosis was(17.4±9.0)%,significantly lower than baseline(t=52.9,P＜0.05),with a mean difference of 65.8%(95%CI63.3%-68.3%).(3)Among all 76patients,one patient developed a flow limiting dissection post balloon angioplasty,which recovered after stent deployment.One patient with basilar artery stenosis experienced recurrent ischemic stroke at 5-day postoperatively,presenting with right sided weakness and coughing on liquids.Imaging showed an acute infarct in the left pons,considered perforator occlusion.The overall periprocedural complication rate was 2.6%(2/76).(4)No deaths occurred within 30 days after surgery.Sixty nine patients(90.8%)underwent 6 month imaging follow up with DSA(52 cases)or CTA(17 cases).ISR occurred in 12 patients(17.4%),including 6 asymptomatic and 6symptomatic cases.The ipsilateral ischemic stroke recurrence rate was 6.6%(5/76)at1 year and13.2%(10/76)at2years.Conclusions Neuroform EZstent assisted PTASappears safe and feasible for the treatment of severe sICAS.The long term effectiveness requires confirmation in large,multicenter,prospective studies.

Objective To evaluate the safety and efficacy of the Neuroform EZ self expanding stent for severe symptomatic intracranial atherosclerotic stenosis(sICAS).Methods Retrospectively enrolled consecutive patients with severe sICAS who underwent percutaneous transluminal angioplasty and stenting(PTAS)with a Neuroform EZ stent in the Department of Cerebrovascular Disease,Henan Provincial People's Hospital,from March 2020 to December 2022.Baseline demographic and clinical data were collected,including age,sex,hypertension,diabetes mellitus,coronary artery disease,dyslipidemia,hyperhomocysteinemia,transient ischemic attack(TIA)and ischemic stroke,smoking history,modified Rankin scale(mRS)score at admission,and National Institutes of Health stroke scale(NIHSS)score.Preoperative imaging data included target vessel(basilar artery,intracranial segment of the internal carotid artery,middle cerebral artery,and intracranial vertebral artery),lesion length,degree of stenosis,and vascular morphology according to the Mori classification(type A,lesion length＜5 mm with concentric or moderately eccentric stenosis;type B,lesion length＜10 mm with severely eccentric stenosis;type C,lesion length＞10 mm or arterial angulation＞90°).Technical success was defined as accurate delivery and deployment of the stent with complete coverage of the target lesion and immediate post deployment residual stenosis＜50%.Postoperative head CT was performed to detect intracranial hemorrhage.Periprocedural complications were recorded,including intracranial hemorrhage,arterial dissection,in stent thrombosis,and perforator occlusion occurring intraoperatively within 72 hours after the procedure.At one-month post-operation,patients were seen through outpatient follow-up for TIA,hemorrhagic or ischemic stroke,and all cause death.At 6 months after surgery,DSA or CT angiography(CTA)was performed to assess in stent restenosis(ISR,defined as＞50%stenosis within the stent or within5mm of its edges,or＞20%luminal loss).At 1 and 2 years postoperatively,ipsilateral ischemic stroke or TIA recurrence was assessed by outpatient visit or telephone follow up.Results A total of 76 patients with severe sICAS underwent PTAS with a Neuroform EZ stent(56 males,20 females,age 47-80 years,with a mean age of[61±10]years).(1)Within all patients enrolled,40 had middle cerebral artery,16 with basilar artery,6 with intracranial vertebral artery and 14 with intracranial internal carotid artery.The preprocedural lesion length was 2-15 mm,with a mean length of(6.2±2.5)mm,and stenosis severity was70%-99%,the mean severity was(83.2±6.9)%,with Mori type B being the most common type(57.9%[44/76]).(2)PTAS was successfully completed on all patients(technical success 100%).Pre dilation with a conventional balloon was performed in all cases(using balloon with diameter of 1.5-3.5mm,and stent with diameter of 2.5-4.5 mm and length of 15-30 mm).Immediate post procedural residual stenosis was(17.4±9.0)%,significantly lower than baseline(t=52.9,P＜0.05),with a mean difference of 65.8%(95%CI63.3%-68.3%).(3)Among all 76patients,one patient developed a flow limiting dissection post balloon angioplasty,which recovered after stent deployment.One patient with basilar artery stenosis experienced recurrent ischemic stroke at 5-day postoperatively,presenting with right sided weakness and coughing on liquids.Imaging showed an acute infarct in the left pons,considered perforator occlusion.The overall periprocedural complication rate was 2.6%(2/76).(4)No deaths occurred within 30 days after surgery.Sixty nine patients(90.8%)underwent 6 month imaging follow up with DSA(52 cases)or CTA(17 cases).ISR occurred in 12 patients(17.4%),including 6 asymptomatic and 6symptomatic cases.The ipsilateral ischemic stroke recurrence rate was 6.6%(5/76)at1 year and13.2%(10/76)at2years.Conclusions Neuroform EZstent assisted PTASappears safe and feasible for the treatment of severe sICAS.The long term effectiveness requires confirmation in large,multicenter,prospective studies.

BACKGROUND:Cervical rotation-traction manipulation is effective and safe in the treatment of cervical spondylotic radiculopathy,and has been widely used in clinical work.However,its effects on the biomechanics of cervical vertebra and intervertebral disc and the area of intervertebral foramen have not been systematically clarified. OBJECTIVE:Based on the finite element analysis technique,a relevant research and analysis were carried out to provide digital evidence for the mechanism of effect of cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy. METHODS:The CT image data of a volunteer with no neck diseases were selected as the finite element model material at its left-handed physiological limit position.The initial construction of the finite element model was completed by Mimics 19.0 software,Geomagic Studio 2013 software,Hypermash 14.0 software,and ANSYS Workbench 2020 R2 software,respectively.Based on the literature,the grid division of cervical structure and the assignment of elastic modulus and elastic coefficient were completed.Based on the previous work of the team,the mechanical effects of cervical rotation-traction manipulation were simulated on the model.Effects of cervical rotation-traction manipulation on the mechanical parameters of each vertebral body and intervertebral disc in C3-T1 segment and on the cervical lateral foramen area were analyzed. RESULTS AND CONCLUSION:(1)During cervical rotation-traction manipulation,the stress of bone structure was significantly higher than that of soft tissue such as intervertebral disc.(2)When operating the technique,the stress at the top of each cervical vertebra was higher,the stress at the bottom was lower,and the stress at the facet joint and transverse process was lower.The stress at the top of the intervertebral disc was lower,the stress at the bottom was higher,but the highest point of the intervertebral disc stress was outside the top.(3)In addition,after loading the lifting force,the projected area of the C6/C7 intervertebral foramen increased significantly compared with that before loading.(4)It is indicated that the cervical rotation-traction manipulation has the mechanical characteristics of changing the stress structure of the cervical spine itself,and can expand the C6/7 intervertebral cervical foramen area on the opposite side of the patient's cervical rotation,so as to achieve the purpose of treating cervical spondylotic radiculopathy.

Objective:To construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma（UTUC）and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them，69（69.7%）were male and 30（30.3%）were female，with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology，tumors staged ≥ T 2 were assigned to the muscle-invasive group，and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data，pathological information，and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC，and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic（ROC）curves，calibration curves，and decision curve analysis（DCA）. Results:Among the 99 patients，70（70.7%）were diagnosed with muscle-invasive UTUC，and 29（29.3%）with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size［4.5（2.8，7.0）cm vs. 3.0（2.3，4.5）cm， P = 0.029］，a higher incidence of multifocal tumors［37.1%（26/70）vs. 3.5%（1/29）， P < 0.001］，patchy tumors［30.0%（21/70）vs. 6.9%（2/29）， P = 0.019］，spiculated tumor margins［52.9%（37/70）vs. 17.2%（5/29）， P = 0.001］，tumor compression on renal parenchyma or periureteral/peripelvic fat［68.6%（48/70）vs. 10.3%（3/29）， P < 0.001］，high-grade pathology［92.9%（65/70）vs. 75.9%（22/29）， P = 0.043］，lymph node metastasis［28.6%（20/70）vs. 0， P = 0.001］，and lymphovascular invasion［42.9%（30/70）vs. 10.3%（3/29）， P=0.002］. The apparent diffusion coefficient（ADC）values［0.9（0.8，1.1）× 10 -3 mm2/s vs. 1.1（1.0，1.4）× 10 -3 mm2/s， P < 0.001］and normalized ADC（NADC）values［0.8（0.7，1.0）vs. 0.9（0.8，1.1）， P = 0.002］were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality，patchy tumor patterns，spiculated tumor margins，tumor compression on renal parenchyma or periureteral/peripelvic fat，and low NADC values as risk factors for muscle-invasive UTUC（all P < 0.05）. Multivariate analysis revealed multifocality（ OR = 17.903，95% CI 1.650 - 194.253， P = 0.018），tumor compression on renal parenchyma or perirenal / ureteral fat（ OR = 14.690，95% CI 3.069 - 70.323， P < 0.001），and low NADC value（ OR = 0.016，95% CI 0.001 - 0.471， P = 0.017）as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve（AUC）of the model was 0.898（95% CI 0.838 - 0.957），with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%，sensitivity of 81.4%，and specificity of 89.7%. Calibration curves indicated good calibration，and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features，including tumor multifocality，compression on renal parenchyma or periureteral/peripelvic fat and NADC value，which demonstrates good predictive performances for muscle-invasive UTUC.

Objective:To construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma（UTUC）and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them，69（69.7%）were male and 30（30.3%）were female，with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology，tumors staged ≥ T 2 were assigned to the muscle-invasive group，and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data，pathological information，and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC，and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic（ROC）curves，calibration curves，and decision curve analysis（DCA）. Results:Among the 99 patients，70（70.7%）were diagnosed with muscle-invasive UTUC，and 29（29.3%）with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size［4.5（2.8，7.0）cm vs. 3.0（2.3，4.5）cm， P = 0.029］，a higher incidence of multifocal tumors［37.1%（26/70）vs. 3.5%（1/29）， P < 0.001］，patchy tumors［30.0%（21/70）vs. 6.9%（2/29）， P = 0.019］，spiculated tumor margins［52.9%（37/70）vs. 17.2%（5/29）， P = 0.001］，tumor compression on renal parenchyma or periureteral/peripelvic fat［68.6%（48/70）vs. 10.3%（3/29）， P < 0.001］，high-grade pathology［92.9%（65/70）vs. 75.9%（22/29）， P = 0.043］，lymph node metastasis［28.6%（20/70）vs. 0， P = 0.001］，and lymphovascular invasion［42.9%（30/70）vs. 10.3%（3/29）， P=0.002］. The apparent diffusion coefficient（ADC）values［0.9（0.8，1.1）× 10 -3 mm2/s vs. 1.1（1.0，1.4）× 10 -3 mm2/s， P < 0.001］and normalized ADC（NADC）values［0.8（0.7，1.0）vs. 0.9（0.8，1.1）， P = 0.002］were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality，patchy tumor patterns，spiculated tumor margins，tumor compression on renal parenchyma or periureteral/peripelvic fat，and low NADC values as risk factors for muscle-invasive UTUC（all P < 0.05）. Multivariate analysis revealed multifocality（ OR = 17.903，95% CI 1.650 - 194.253， P = 0.018），tumor compression on renal parenchyma or perirenal / ureteral fat（ OR = 14.690，95% CI 3.069 - 70.323， P < 0.001），and low NADC value（ OR = 0.016，95% CI 0.001 - 0.471， P = 0.017）as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve（AUC）of the model was 0.898（95% CI 0.838 - 0.957），with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%，sensitivity of 81.4%，and specificity of 89.7%. Calibration curves indicated good calibration，and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features，including tumor multifocality，compression on renal parenchyma or periureteral/peripelvic fat and NADC value，which demonstrates good predictive performances for muscle-invasive UTUC.

AIM:To investigate the effect of vaccarin(VAC)on endothelial dysfunction in type 2 diabetes mellitus(T2DM),and to uncover the underlying mechanisms.METHODS:(1)C57BL/6 mice received intraperitoneal injection of streptozotocin and were fed with a high-fat diet(21.8 kJ/kg,60%of the energy source was fat)to construct a T2DM mouse model.Thirty mice were randomly divided into control,T2DM and T2DM+VAC groups,with 10 mice in each group.The mice in T2DM+VAC group were given 1 mg/kg VAC via oral gavage for 6 weeks,while those in control and T2DM groups were given the same volume of PBS.The mRNA and protein expression levels of BCL2-interacting pro-tein 3(BNIP3),PTEN-induced kinase 1(PINK1)and parkin in the thoracic aorta were detected by RT-qPCR and West-ern blot.(2)Human umbilical vein endothelial cells(HUVECs)were stimulated by high glucose(HG;35 mmol/L glu-cose).Mitochondrial membrane potential,autophagy and mitochondrial superoxide levels were detected using JC-1,acri-dine orange(AO)and MitoSOX staining,respectively.RESULTS:Compared with control group,the mRNA and protein levels of BNIP3,PINK1 and parkin were significantly increased in the thoracic aorta of T2DM mice(P<0.05).Compared with T2DM group,the mRNA and protein levels of BNIP3,PINK1 and parkin in the thoracic aorta were significantly re-duced in T2DM+VAC group(P<0.05).The results of JC-1,AO and MitoSOX staining showed that VAC attenuated the decrease in mitochondrial membrane potential and the increase in autophagy and mitochondrial superoxide levels in HG-in-duced HUVECs.Treatment with VAC also inhibited HG-mediated mitochondrial damage in HUVECs after BNIP3 overex-pression.The effect of miR-570-3p mimic on mitochondrial damage was similar to VAC.RT-qPCR and Western blot showed that both miR-570-3p mimic and VAC significantly reduced the mRNA and protein levels of BNIP3,PINK1 and parkin.In contrast,inhibition of miR-570-3p exhibited the opposite effects.CONCLUSION:Treatment with VAC alle-viated endothelial dysfunction in T2DM by inhibiting HG-induced mitochondrial dysfunction through miR-570-3p/BNIP3.

Acute kidney injury(AKI)remains a global public health problem with high incidence,high mortality rates,expensive medical costs,and limited treatment options.AKI can further progress to chronic kidney disease(CKD)and eventually end-stage renal disease(ESRD).Previous studies have shown that trauma,adverse drug reactions,surgery,and other factors are closely associated with AKI.With further in-depth exploration,the role of gut microbiota in AKI is gradually revealed.After AKI occurs,there are changes in the composition of gut microbiota,leading to disruption of the intestinal barrier,intestinal immune response,and bacterial translocation.Meanwhile,metabolites of gut microbiota can exacerbate the progression of AKI.Therefore,elucidating the specific mechanisms by which gut microbiota is involved in the occurrence and development of AKI can provide new insights from the perspective of intestinal microbiota for the prevention and treatment of AKI.

With the widespread use of CT scan in lung cancer screening,in clinical practice the detection rate of pulmonary ground-glass nodule(GGN),especially multiple GGNs,has become higher and higher.So far,the guidelines for the treatment of multiple pulmonary nodules mainly focus on the high-risk nodules,while there is no uniform guideline for the management of multiple high-risk GGNs.The main treatment strategies for GGNs include follow-up check and surgical resection.However,for patients who are unable to undergo or refuse to receive surgery,non-surgical therapies such as stereotactic body radiation therapy(SBRT),interventional ablation(such as radiofrequency ablation,micro wave ablation,cryoablation,etc.)can be considered.This article reviews the clinical management strategies and therapeutic evaluation of multiple pulmonary nodules,aiming to provide reference for the clinical management of multiple pulmonary nodules.

Objective To explore the risk factors and countermeasures of the perfusionist-related near-miss event (NME) in cardiopulmonary bypass (CPB). Methods The clinical data of the patients who underwent cardiac surgery in the Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University from March 2020 to July 2021 were retrospectively analyzed. According to whether NME occurred during the operation, the patients were divided into an NME group and a non-NME group. The clinical data of the two groups were compared, and the risk factors for NME were analyzed. Results A total of 702 patients were enrolled, including 424 males and 278 females with a median age of 56.0 years. There were 125 patients in the NME group and 577 patients in the non-NME group. The occurrence rate of NME was 17.81%. Univariate analysis showed that there were statistical differences between the two groups in the gender, body surface area, CPB time, European system for cardiac operative risk evaluation score, emergency surgery, type of surgery, night CPB initiation, modified ultrafiltration use, multi-device control, average operation time, et al. (all P<0.05). The above variables were dimensionality reduction processed by least absolute shrinkage and selection operator regression, and the λ of minimum mean square error of 10-fold cross validation was 0.014. The variables of the corresponding model were selected as follows: multi-device control, night CPB initiation, minimum hematocrit, modified ultrafiltration use, CPB time. The results of multivariate logistic regression showed that night CPB initiation [OR=9.658, 95%CI (4.735. 19.701), P<0.01] and CPB time [OR=1.003, 95%CI (1.001, 1.006), P=0.014] were independent risk factors for NME. Conclusion Night CPB initiation and CPB time are independent risk factors for NME during CPB, which should be recognized and early warned in clinical work.