Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

AIM:To investigate the therapeutic effect of Qingre sanzhuo decoction on rats with hyperuri-caemia combined with gouty arthritis and its effect on TLR4/Myd88/NF-κB signalling pathway.METHODS:Forty-eight SD male rats were randomly divided into blank,model,and colchicine groups(0.3 mg·kg-1·d-1),and Origre sanzhou decotion low,medium and high-dosage groups(7.42,14.85,29.70 g·kg-1·d-1),which were treated with the modified Coderre method for hyperuricemia combined with acute gouty arthritis via gavage of yeast paste combined with potassium oxa-late,which was used for the treatment of acute gouty arthritis combined with hyperuricemia.A composite rat model of acute gouty arthritis was constructed by combining yeast paste with potassium oxalate gavage to cause hyperuricaemia,combined with the modified Coderre method.After 7 days of intervention,the circumference of the right ankle joint of rats was measured and the swelling of the ankle joint was calculated,the blood uric acid(HUA)level of rats was determined by biochemical method,the histopatho-logical and morphological changes of the synovial membrane of the ankle joint of rats were examined by HE staining,and the serum levels of inflammatory factors,tumour necrosis factor-alpha(TNF-α),inter-leukin-6(IL-6),and IL-1β were determined by enzyme-linked immunosorbent assay(ELISA),and Western blotting was performed to determine the levels of inflammatory factors,TNF-α,and IL-1β.The protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(Myd88),and nuclear factor-κB(NF-κB)in the synovial tissues of the ankle joints of the rats were determined by Western blot method,and the mRNA expression of TLR4,Myd88,and NF-κB in the rat was determined by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).RESULTS:Compared with the blank group,rats in the model group showed significantly lower ankle joint swelling(P<0.01),increased levels of HUA,dis-organised synovial tissue structure,large number of inflammatory cells infiltration,and significantly higher serum levels of TNF-α,IL-6,and IL-1β(P<0.01),and the protein and mRNA expression levels of TLR4,Myd88,and NF-κB in the synovial membrane of the ankle joints of the model group were significantly increased(P<0.01).levels were significantly increased(P<0.01);compared with the model group,joint swelling was significantly reduced in the colchicine group,and the medium-and high-dose groups of Qingre sanzhuo decoction(P<0.05);synovial hyperplasia and inflam-matory cell infiltration were improved in the colchicine group and the medium-and high-dose groups of Qingre sanzhuo decoction,and the HUA and the levels of TNF-α,IL-6,and IL-1β were significantly decreased in the dosing groups(P<0.05,P<0.01),and compared with the model group,the medium-and high-dose groups of Qingre sanzhuo decoction could significantly reduce the expression of TLR4,Myd88,and NF-κB protein and mRNA(P<0.01).CONCLUSION:Qingre sanzhuo decoction reduces the release of inflamma-tory factors by inhibiting the TLR4/Myd88/NF-κB pathway,and plays a role in the treatment of hyper-uricaemia combined with gouty arthritis.

Smart healthcare plays an important role in easing the strain on medical resources and improving the continuity of chronic disease management. This study analysed the iatrogenic risks from the intrinsic attributes and the external environment of smart healthcare, including doctor-patient conflict risk, technical operation risk, information leakage risk, humanistic absence risk, legal risk, regulatory risk and ethical risk. Based on the " structure process result" model, suggestions were proposed to optimize the construction of a smart healthcare platform for chronic diseases, improve the legal system and industry standards, strengthen talent cultivation and capacity building, establish an integrated regulatory system, and regularly evaluate the effectiveness of chronic disease management. These suggestions provided references for creating a healthy, orderly, and safe smart healthcare environment for chronic disease patients.

Objective:To explore the expression of YARS1, the subform of protein-based tRNA synthase ( YARS1), and its prognostic effect on the analysis of gene set enrichment in hepatocellular carcinoma Methods:The expressional condition of the YARS1 gene in tumor tissue samples (374 cases) and adjacent tissue samples (50 cases) of hepatocellular carcinoma patients was compared and recorded by mining the Cancer Genome Atlas database. Hepatocellular carcinoma patients were divided into high expression and low expression groups according to this data. Logistic regression was used to analyze the relationship between YARS1 and the clinical pathological characteristics of hepatocellular carcinoma patients. The effect of YARS1 expression on the prognosis of hepatocellular carcinoma patients was analyzed by the Kaplan-Meier method and log-rank test. The prognostic value of the YARS1 gene for hepatocellular carcinoma was analyzed by univariate and multivariate Cox regression. Gene set enrichment analysis was used to evaluate the gene pathways related to YARS1 in the occurrence and development of hepatocellular carcinoma. Results:The expression of the YARS1 gene was higher in hepatocellular carcinoma tissue than in normal tissue ( P<0.001). The expression level of YARS1 was correlated with the grade of patients ( P<0.05), but not with age, gender, TNM stage, and others ( P>0.05). The results of Kaplan-Meier method and log-rank test showed that the survival rate was lower in patients with high YARS1 gene expression than that of patients with low YARS1 gene expression ( P<0.001). The results of multivariate Cox regression analysis showed that YARS1 was used as an independent prognostic factor for hepatocellular carcinoma [hazard ratio=1.10, 95% confidence interval (1.050-1.156), P<0.001]. The results of gene set enrichment analysis showed that YARS1 was involved in pyrimidine metabolism, purine metabolism, aminoacyl tRNA biosynthesis, fatty acid metabolism, ppar signal transduction pathway, oocyte meiosis, amino acid and nucleotide sugar metabolism, RNA degradation, complement pathway, valine and isoleucine degradation, spliceosome, and other pathways. Conclusion:The high expression of YARS1 is associated with the progression and prognosis of hepatocellular carcinoma. Therefore, this gene is expected to become a novel biomarker and a sort of target for biological therapy in hepatocellular carcinoma.

Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

Aim To investigate the effect of cordycepin(COR)on gentamicin(GEN)-induced nephrotoxicity and the molecular mechanism of inhibiting oxidative stress and ferroptosis induced by GEN.Methods The oral SD rats were divided into a control group,GEN group,and GEN+COR group.Following the success-ful setting up of the animal model,the serum creatinine(CR)and urea nitrogen(BUN)levels of rats were measured,and renal tissue injury was assessed using HE staining.In addition,the contents of malondialde-hyde and glutathione in kidney tissues of SD rats in each group were detected,and the expressions of fer-roptosis markers GPX4 and SLC7A11 were analyzed by Western blot.Results Compared with the control group,CR and BUN in GEN-stimulated group signifi-cantly increased(P＜0.01),and the level of CR and BUN was effectively reduced after 50 mg·kg-1 COR oral administration.HE results also showed that COR could alleviate the kidney tissue damage caused by GEN.COR could reverse the increase of malondialde-hyde level and the decrease of glutathione level caused by GEN in rat kidney tissue,and COR could restore the decrease of GPX4 and SLC7A11 protein levels induced by GEN.Conclusion COR can reduce GEN-induced kidney injury by inhibiting oxidative stress and ferrop-tosis.

Objective:To investigate the effect of extracorporeal membrane oxygenation (ECMO) in assisting neonates with complex congenital heart diseases (CHD) and the survival rate of the patients.Methods:A retrospective case-control study was made on 22 newborns with complex CHD assisted by ECMO during the perioperative period in Fuwai Central China Cardiovascular Hospital from January 2018 to June 2024.There were 19 males and 3 females in the newborns included, with an average age of (10.4±8.7) days (range: 1-26 days) and an average weight of (3.1±0.3) kg.Complex CHD included total anomalous pulmonary venous connection in 9 cases (40.9%), interrupted aortic arch and coarctation in 8 cases (36.4%), transposition of great arteries in 3 cases (13.6%), double outlet right ventricle in 1 case (4.5%) and cardiac tumor in 1 case (4.5%).The patients were divided into the <5 d group, 5-12 d group, and >12 d group according to the duration of ECMO support.Data were compared using the t-test or χ2 test. Results:There were 8 cases (36.4%) successfully weaned from ECMO support and 6 cases (27.3%) survived.ECMO support was used routinely in 15 cases (68.2%), and for extracorporeal cardiopulmonary resuscitation in 7 cases (31.8%).The duration of ECMO support was (5.9±3.7) days.There were no statistically differences in age, weight, gender, disease composition, operation time, cardiopulmonary bypass time, cross-clamp time, assistant time, blood routine, liver and kidney function and other biochemical indicators, preoperative cardiac ejection fraction value, procalcitonin, C-reactive protein and other infection indicators between the death group and the survival group (all P>0.05).The highest lactate values 24 hours before [(8.1±5.4) mmol/L] and after ECMO support [(10.5±7.1) mmol/L] in the survival group were significantly lower than those in the death group [(18.7±9.2) mmol/L, (21.3±8.6) mmol/L] ( t=2.606, P=0.018; t=2.729, P=0.013).It was found that the survival rate was 0/9 (0) in the <5 d group, 6/12 (50.0%) in the 5-12 d group, and 0/1 (0) in the >12 d group.The survival rate of the 5-12 d group was the highest, which was significantly higher than that of the <5 d group ( χ2=6.300, P=0.012). Conclusions:ECMO support is an effective treatment for severe circulatory failure in neonates with complex CHD in the perioperative period.The highest lactate levels 24 hours before and after ECMO support affect the survival rate.Patients receiving 5-12 d ECMO support can achieve the highest survival rate.

Purpose To characterize the clinicopathological features of gastrointestinal mesenchymal tumors(GMTs)resected via endoscopic techniques.Methods A retrospective analysis was conducted on 495 cases of endo-scopically resected GMTs.Clinical information,histomorphological findings,immunohistochemical profiles,and mo-lecular characteristics were reviewed.Results The cohort included 495 patients aged 20-78 years(median:53 years).The majority of tumors were located in the stomach(58.8％)and esophagus(36.8％).Histologically,most tumors consisted of spindle cells,with a minority composed of epithelioid cells;fibrocollagenous or myxoid stroma was occasionally observed.Immunohistochemically,leiomyomas showed diffuse positivity for α-SMA(98.8％)and desmin(99.3％),gastrointestinal stromal tumors(GISTs)expressed CD117(99.4％),DOG1(97.6％),and CD34(97.0％),and schwannomas were positive for S-100(93.7％).The predominant tumor types were leiomyomas(54.1％)and GISTs(33.7％),while the remaining 12.2％comprised other rare types.Various endoscopic resection techniques were employed based on the tumors' anatomical depth,including endoscopic submucosal dissection(ESD,40.5％),submucosal tunneling endoscopic resection(STER,17.1％),endoscopic mucosal resection(EMR,16.5％),endoscopic full-thickness resection(EFTR,13.9％),and endoscopic submucosal excavation(ESE,12.0％).EMR and ESD were primarily used for superficial lesions,while deeper tumors with were more often treated with STER,EFTR,and ESE.The rate of negative resection margins was lower in GISTs(72.2％)and other tumors with indistinct margins,compared to leiomyomas(92.6％)and those with well-defined boundaries.Conclusion Leiomyomas and GISTs are the most common gastrointestinal mesenchymal tumors resected via endoscopy.A variety of resection techniques are applicable depending on tumor location and depth.Accurate pathological diagnosis should be based on HE morphology,supplemented by endoscopic findings,margin status,immunohistochemistry,and necessary molecular tests.

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*