Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine （SCOP） and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups： control （0.9% NaCl， n=10）， model （SCOP 1 mg·kg^-1·d^-1， n=10）， low-， medium-， and high-dose Dihuang Yinzi （SCOP 1 mg·kg^-1·d^-1 + Dihuang Yinzi 5.5， 11.0， and 22.0 g·kg^-1·d^-1， n=10）， and donepezil （SCOP 1 mg·kg^-1·d^-1 + donepezil 0.84 mg·kg^-1·d^-1， n=10）. Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week， and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week， 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 （SIRT2）， α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid （AMPA） receptor 1 （GluA1）， protein kinase A （PKA）， cAMP response element-binding protein （CREB）， phosphorylated-CREB （p-CREB）， postsynaptic density protein 95 （PSD95）， growth-associated protein-43 （GAP-43）， and synaptophysin （SYN） in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin （DCX） in the hippocampal dentate gyrus （DG） region. ResultsCompared with the control group， the model group showed impaired learning and memory （P<0.01）， obvious neuronal damage in the hippocampal CA1 region， a reduction in neuron survival （P<0.01）， a decrease in DCX expression in the hippocampal DG region （P<0.01）， down-regulated proteins levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 in the hippocampal tissue （P<0.05， P<0.01）， and an up-regulated protein level of SIRT2 （P<0.01）. Compared with the model group， the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory （P<0.05， P<0.01）， while the low-， medium-， and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival （P<0.05， P<0.01）. The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression （P<0.05， P<0.01）. The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 （P<0.05， P<0.01） and down-regulation in the protein level of SIRT2 （P<0.01）. ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2， activating the PKA/CREB signaling pathway， improving synaptic plasticity， and reducing hippocampal neuronal damage.

Objective To investigate how vismodegib(Vis)influences the pathogenesis of basal cell carcinoma(BCC)via a chromatin remodeling factor,bromodomain containing protein 9(BRD9),and to analyze the expression profile of BRD9 in BCC and its relationship with the immune checkpoint,programmed cell death-1 ligand 1(PD-L1)and the Hedgehog(Hh)signaling pathway.Methods ① A UVB-induced BCC model was established in SKH-1 hairless background Ptch1+/-;LacZ reporter mice.Then the mice were treated with Vis,and those without treatment served as control.X-gal staining,immunohistochemistry(IHC)staining,immunofluorescence(IF)assay,and Western blotting were used to assess the expression and localization of BRD9 and PD-L1 in tumor tissues and to evaluate immune-cell infiltration.② In vitro,mouse BCC cell line ASZ001(ASZ cells)were treated with Vis or a BRD9 degrader(dBRD9),and BRD9-overexpressing cells were generated.Cell viability and the protein and mRNA levels of BRD9,PD-L1,Gli1,and cyclin D1(Ccnd1)were measured.ChIP-qPCR was performed to examine BRD9 and H3K27ac enrichment at the PD-L1 promoter,including the promoter-proximal site(P1)and an upstream active segment(P2).Results ① At the tissue level,BRD9 was highly expressed in BCC,and co-localization of BRD9 and PD-L1 was observed within tumor regions,with evident immune-cell infiltration.Vis markedly suppressed UVB-induced BCC formation,reduced the probability of large-volume tumors(by probability-density analysis),decreased the X-gal-positive lesion area(P<0.000 1),down-regulated BRD9(P=0.024 9),and attenuated immune-cell infiltration.② At the cellular level,Vis treatment reduced cell viability and down-regulated BRD9,Gli1,and Ccnd1 in ASZ cells(P<0.000 1).dBRD9 inhibited ASZ cell viability in a dose-dependent manner and decreased PD-L1,Gli1,and Ccnd1(P<0.000 1),whereas its overexpression increased the expression of these molecules(P<0.000 1).In ASZ cells,BRD9 and H3K27ac were enriched at the PD-L1 promoter P1/P2 regions.Treatment with dBRD9 or Vis reduced BRD9 and H3K27ac enrichment at P1/P2 regions(P<0.000 1).Conclusion In BCC,BRD9 maintains chromatin activation at the proximal PD-L1 promoter and modulates Hh/Gli1 signaling,thereby promoting immune evasion.Vis remodels the tumor immune microenvironment by inhibiting the Hh-BRD9-PD-L1 axis.

Objective To analyze the efficacy of the"sandwich"technique for treating varicocele(VC).Methods A total of 310 patients with VC(365 affected veins)were selected and divided into interventional treatment group and non-interventional treatment group.The baseline data,hospitalization data,and 6-month follow-up data of the two groups were analyzed.Results The age of patients in the interventional treatment group was significantly lower than that in the non-interventional treatment group(P＜0.05).The surgical time and hospital stay in the interventional treatment group were significantly lower than those in the non-interventional treatment group(P＜0.05).In the non-interventional treatment group,two patients experienced surgical site infections,and one patient opted for interventional treatment due to recurrence after non-interventional treatment.After surgery,the diameter of the spermatic vein significantly decreased in both the interventional and non-interventional treatment(P＜0.05).Conclusion The"sandwich"technique(embolization coil combined with foam sclerotherapy)is an effective treatment for VC.

Objective:To investigate the differential expression profiles of long non-coding RNAs(LncRNAs) and messenger RNAs(mRNAs) regulated by soluble dipeptidyl peptidase-4(sDPP4) during vascular smooth muscle cell calcification, and to explore the potential underlying calcification mechanisms.Methods:DPP4 levels in blood vessels and peripheral blood of diabetic patients were measured using Western blotting(WB) and real-time quantitative PCR(RT-qPCR). A cellular calcification model was established by treating human aortic vascular smooth muscle cells(HASMCs) with sDPP4. The effects of sDPP4 on HASMCs were assessed by WB, RT-qPCR, alizarin red staining, and calcium content determination. High-throughput sequencing was performed to analyze the differential expression profiles of LncRNA and mRNA following sDPP4 treatment. Among them, LncRNA ENST00000540293, which exhibited the most pronounced downregulation and was located adjacent to the matrix metalloproteinase-1(MMP-1) gene, was selected for further investigation. The osteogenic transdifferentiation of HASMCs after silencing LncRNA ENST00000540293 was evaluated using WB, RT-qPCR, alizarin red staining, and immunofluorescence-based cytoskeletal staining.Results:DPP4 expression was significantly elevated in both blood vessels and peripheral blood of diabetic patients. sDPP4 stimulation upregulated the protein levels of osteopontin(OPN) and runt-related transcription factor 2(RUNX2) in HASMCs, enhanced alizarin red staining, and increased intracellular calcium deposition. RNA sequencing revealed significant downregulation of LncRNA ENST00000540293 following sDPP4 exposure, while GO and pathway analysis indicated a marked increase in extracellular matrix binding activity(GO: 0050840). Silencing LncRNA ENST00000540293 suppressed α-smooth muscle actin(α-SMA) expression, promoted OPN and RUNX2 expression, increased calcification as shown by positive alizarin red staining, and cytoskeletal staining demonstrated osteogenic transdifferentiation of HASMCs, accompanied by a significant rise in MMP-1 protein level.Conclusion:sDPP4 promotes osteogenic transdifferentiation of HASMCs, potentially by downregulating LncRNA ENST00000540293. MMP-1 may be a potential target regulated by LncRNA ENST00000540293.

Objective:To investigate the differential expression profiles of long non-coding RNAs(LncRNAs) and messenger RNAs(mRNAs) regulated by soluble dipeptidyl peptidase-4(sDPP4) during vascular smooth muscle cell calcification, and to explore the potential underlying calcification mechanisms.Methods:DPP4 levels in blood vessels and peripheral blood of diabetic patients were measured using Western blotting(WB) and real-time quantitative PCR(RT-qPCR). A cellular calcification model was established by treating human aortic vascular smooth muscle cells(HASMCs) with sDPP4. The effects of sDPP4 on HASMCs were assessed by WB, RT-qPCR, alizarin red staining, and calcium content determination. High-throughput sequencing was performed to analyze the differential expression profiles of LncRNA and mRNA following sDPP4 treatment. Among them, LncRNA ENST00000540293, which exhibited the most pronounced downregulation and was located adjacent to the matrix metalloproteinase-1(MMP-1) gene, was selected for further investigation. The osteogenic transdifferentiation of HASMCs after silencing LncRNA ENST00000540293 was evaluated using WB, RT-qPCR, alizarin red staining, and immunofluorescence-based cytoskeletal staining.Results:DPP4 expression was significantly elevated in both blood vessels and peripheral blood of diabetic patients. sDPP4 stimulation upregulated the protein levels of osteopontin(OPN) and runt-related transcription factor 2(RUNX2) in HASMCs, enhanced alizarin red staining, and increased intracellular calcium deposition. RNA sequencing revealed significant downregulation of LncRNA ENST00000540293 following sDPP4 exposure, while GO and pathway analysis indicated a marked increase in extracellular matrix binding activity(GO: 0050840). Silencing LncRNA ENST00000540293 suppressed α-smooth muscle actin(α-SMA) expression, promoted OPN and RUNX2 expression, increased calcification as shown by positive alizarin red staining, and cytoskeletal staining demonstrated osteogenic transdifferentiation of HASMCs, accompanied by a significant rise in MMP-1 protein level.Conclusion:sDPP4 promotes osteogenic transdifferentiation of HASMCs, potentially by downregulating LncRNA ENST00000540293. MMP-1 may be a potential target regulated by LncRNA ENST00000540293.

Objective To analyze the efficacy of the"sandwich"technique for treating varicocele(VC).Methods A total of 310 patients with VC(365 affected veins)were selected and divided into interventional treatment group and non-interventional treatment group.The baseline data,hospitalization data,and 6-month follow-up data of the two groups were analyzed.Results The age of patients in the interventional treatment group was significantly lower than that in the non-interventional treatment group(P＜0.05).The surgical time and hospital stay in the interventional treatment group were significantly lower than those in the non-interventional treatment group(P＜0.05).In the non-interventional treatment group,two patients experienced surgical site infections,and one patient opted for interventional treatment due to recurrence after non-interventional treatment.After surgery,the diameter of the spermatic vein significantly decreased in both the interventional and non-interventional treatment(P＜0.05).Conclusion The"sandwich"technique(embolization coil combined with foam sclerotherapy)is an effective treatment for VC.

Objective:To compare the efficacy and safety of low-dose and standard-dose radiotherapy (LD-RT vs. SD-RT) in the treatment of oropharyngeal cancer patients with positive human papillomavirus (HPV). Methods:All comparative studies of low-dose versus standard-dose radiotherapy in the treatment of HPV-positive oropharyngeal cancer were searched from PubMed, Web of Science, Cochrane Library, EMbase, Chinese Biomedical Literature Database (CBM), CNKI, Chongqing VIP, and Wanfang databases from January 1, 2000 to February 9, 2023. According to the inclusion and exclusion criteria, the data were strictly screened, and the RevMan 5.4 software was used for meta-analysis.Results:A total of 8 studies were included. The pooled results showed that the overall survival (OS) and progression-free survival (PFS) of patients in the LD-RT group were similar to those in the SD-RT group ( HR=0.83, 95% CI=0.59-1.18, P=0.31; HR=0.97, 95% CI=0.53-1.78, P=0.92), but the rate of percutaneous endoscopic gastrostomy (PEG) insertion was significantly reduced ( RR=0.45, 95% CI=0.28-0.72, P=0.001). Conclusion:LD-RT yields similar efficacy and lower rate of PEG insertion compared with SD-RT in HPV-positive oropharyngeal neoplasm patients.

Objective To observe the effect of in situ needle fenestration thoracic endovascular aortic repair(TEVAR)for treating aortic dissection(AD)involving aortic arch.Methods Data of 16 patients with AD involving aortic arch who underwent in situ needle fenestration TEVAR for reconstruction of aortic arch branches were retrospectively analyzed,and the number of fenestration,technical success rate and TEVAR related complications were recorded.Regular follow-up was conducted after TEVAR,the repair of dissection and the patency of fenestrated branch blood vessels were evaluated,the endoleak was assessed,and the survival of patients were recorded.Results The main aortic stent was successfully implanted in all 16 cases.Among them,4 received triple fenestration stent implantation in zones Z0,Z1 and Z2,6 received double fenestration stent implantation in zones Z1 and Z2,2 received double fenestration stent implantation in zones Z0 and Z1 and 4 received single fenestration stent implantation in zone Z2.The success rate of brachiocephalic trunk(BCT)fenestration was 83.33%(5/6).Left common carotid artery(LCCA)-right common carotid artery bypass was performed in 1 case without successful fenestration.The success rate of LCCA fenestration was 100%(12/12).The success rate of left subclavian artery(LSA)fenestration was 87.50%(14/16),2 cases with not successful fenestration were treated with axillar-axillary artery artificial vascular bypass.The technical success rate of intervention was 100%(16/16).Type Ⅰa endoleak occurred in 1 case during TEVAR process and improved after embolization with spring coil.One patient died of pericardial tamponade at the end of TEVAR.Fifteen patients were followed up for a median follow-up time of 20 months.During this period,transient ischemic attack and local small dissection at the proximal beginning of the main stent occurred each in 1 case,which improved after no special treatment.Type Ⅰ endoleak occurred in 1 case,type Ⅲ endoleak occurred in 2 cases,all improved after proximal fenestrated membrane stent implantation or spring coil embolization treatment.One case died of coronary heart disease.Conclusion In situ needle fenestration TEVAR was effective and safe for treating AD involving aortic arch.

Objective To evaluate the medium-to-long-term efficacy of parallel stenting technology in treating aortoiliac occlusive disease(AIOD).Methods The clinical data of 18 patients with symptomatic AIOD,who received parallel stenting(using metal bare stent or covered stent)to reconstruct the aortoiliac artery at the Affiliated Hospital of Southwest Medical University of China from March 2017 to May 2019,were retrospectively analyzed.The patients included 14 males and 4 females with a mean age of(64.78±9.04)years.The surgical details,clinical success,complications,and stent patency rate were recorded.Results Both technical success and clinical success were achieved in all patients.A total of 62 stents were implanted,including 52 bare metal stents,9 covered stents and one renal artery balloon dilatation stent.After stent implantation,one patient each developed lacunar cerebral infarction,brachial artery pseudoaneurysm,decreased hemoglobin level,and thrombus migration into the renal artery,and after active management the patients were well discharged.The incidence of complications was 22％(4/18).During the follow-up period,3 patients developed in-stent restenosis,and the vascular lumen returned to patency after a second time of endovascular intervention.The postoperative 12-,18-,24-,30-,and 36-month main patency rates were 100％,95％,90％,85％,and 85％,respectively.Conclusion For the treatment of AIOD,parallel stenting technology has obtained satisfactory 3-year results.For the patients with complicated AIOD,this technique also carries a high technical success rate and an acceptable medium-to-long-term patency rate.