OBJECTIVE To evaluate the efficacy and safety of amoxicillin combined with proton pump inhibitor （PPI） or potassium-competitive acid blocker （P-CAB） for Helicobacter pylori （Hp） eradication. METHODS Randomized controlled trial （RCTs） on amoxicillin combined with PPI or P-CAB for Hp eradication were retrieved from PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang， and VIP data. The search time frame was from database inception to September 5， 2025. After literature screening， data extraction， and quality assessment， a network meta-analysis was performed using Stata 17.0 software. RESULTS A total of 12 RCTs involving 5 515 patients were included， encompassing 8 therapeutic regimens： PPI combined with high-dose amoxicillin for 14 days （TR1）， PPI combined with low-dose amoxicillin for 14 days （TR2）， P-CAB combined with high-dose amoxicillin for 7 days （TR3）， P-CAB combined with high-dose amoxicillin for 14 days （TR4）， P-CAB combined with high-dose amoxicillin for 10 days （TR5）， P-CAB combined with low-dose amoxicillin for 7 days （TR6）， P-CAB combined with low-dose amoxicillin for 14 days （TR7）， and P-CAB combined with low-dose amoxicillin for 10 days （TR8）. The network meta-analysis results showed that， in terms of intention-to-treat Hp eradication rates， the eradication rates of TR5 and TR4 were significantly higher than those of TR3， TR8， TR6 and TR1 （ P ＜0.05）. The surface under the cumulative ranking curve （SUCRA） values from highest to lowest were： TR4 （89.7%）＞TR5 （82.3%）＞TR7 （71.5%）＞ TR2 （48.6%）＞TR1 （43.9%）＞TR8 （28.7%）＞TR3 （22.7%）＞TR6 （12.6%）. Regarding safety， the incidence of adverse reactions in TR3 and TR5 was significantly lower than that in TR1 （ P ＜0.05）. The SUCRA values from highest to lowest were： TR1 （91.3%）＞TR4 （79.8%）＞TR5 （55.0%）＞TR7 （50.9%）＞TR8 （41.3%）＞TR2 （36.4%）＞TR3 （27.6%） ＞TR6 （17.7%）. CONCLUSIONS Although the regimen of P-CAB combined with high-dose amoxicillin for 14 days demonstrates the best efficacy， the combination of P-CAB with high-dose amoxicillin for 10 days exhibits a better balanced profile in terms of both efficacy and safety.

Objective To establish a liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination of ginsenoside Rh2(GRh2)in plasma of mice,so as to provide preclinical data support for the pharmacokinetic study and application of GRh2.Methods C57BL16 mice were given 7.5 mg/kg GRh2 by gavage.After administration,0.03 mL of whole blood was collected at 5 min,10 min,15 min,30 min,1 h,2 h,4 h,and 8 h.Then,the whole blood was centrifuged and the serum was treated with 0.1％formic acid acetonitrile,dried by nitrogen(40℃),and redissolved with 50.0 pL 50％methanol solution containing 100 ng/mL diclofenac sodium.After vortex mixing for 5 min at room temperature,it was put into the automatic sampler for sampling analysis.The chromatographic column was Waters BEHC18(2.1 mm × 50.0 mm,1.7 pm),the mobile phase was aqueous solution containing 0.1％formic acid and acetonitrile solution containing 0.1％formic acid at a flow rate of 0.60 mL/min,the column temperature was 40℃,and the injection volume was 1.00 pL.The electric spray ion source,positive ion mode and multiple reaction monitoring mode were performed.A standard curve was established to calculate blood drug concentration.The blood drug concentration-time curve was established according to the blood drug concentration,and the main pharmacokinetic parameters were calculated.Results The linear range of the standard curve of drug containing plasma was 100-40 000 ng/mL,and the correlation coefficient(r)was 0.996 0.After internal standard normalization,the matrix effect factors of GRh2 were 1.09,1.06,and 1.00(between 0.8 and 1.2),indicating no significant matrix effect.The precision and accuracy results showed that the average measured concentration of GRh2 samples at each concentration level was 103,333,23 800 and 35 000 ng/mL,the inter batch standard deviation was 6.47-1 120 ng/mL,the inter batch relative standard deviation was 1.5％-8.3％,and the inter batch accuracy deviation was 93.3％-111.1％.The long-term stability,short-term stability,repeated freeze-thaw property,and extraction recovery rate of GRh2 were all good.The pharmacokinetic parameters Tmax and Cmax of GRh2 in mice were(1.42±1.01)h and(1 251±495)ng/mL,respectively,indicating that the absorption and utilization rate of GRh2 in vivo was high and GRh2 had good drug performance.Conclusion The established LC-MS/MS method is accurate and reliable,and can be used to determine the concentration of GRh2 in mouse plasma and study its pharmacokinetic.

Objective:To analyze the pangenome, pan drug resistance genes, pan virulence genes, pan replicons, and others of the plasmids carried by hypervirulent Klebsiella pneumoniae (hvKP) in the world and their evolutionary trends over time, and provide evidence for more comprehensive understanding of the evolution of genetic diversity, drug resistance genes, and virulence genes of the plasmids. Methods:From the National Center for Biotechnology Information database, a total 1 738 plasmids were screened from 524 strains with completed genome sequences in 2 136 strains of hvKP carrying plasmids. Through pangenome, pan drug resistance gene, and pan-virulence gene composition and functional analyses, the curves of pangenome size and new gene size against plasmid isolation time were established, revealing the diversity of the plasmid pangenome and its evolutionary patterns.Results:The homologous genes, homologous drug resistance genes, homologous virulence genes, and replicons of the plasmids carried by hvKP comprised of 12 906, 149, 107 and 89 types, respectively. The fitting curves for the number of new genes, new drug resistance genes and new replicons increased with the increase of plasmids in an open state, while the curve for novel virulence genes was in a closed state. A obvious increase in new drug resistance genes was observed during 2018-2019. Among the newly added drug resistance genes during 2021-2023, beside those conferring aminoglycoside resistance, they were mainly new subtypes conferring carbapenem resistance.Conclusions:The pangenome of plasmids carried by hvKP exhibited high diversity, with the plasmid pan genes, pan drug resistance genes, and pan replicon types gradually expanding, while the pan virulence genes remains stable. The increase in novel drug resistance genes in specific years and the emergence of new carbapenem-resistant gene subtypes during 2021-2023 suggested the need for strengthened drug resistance surveillance and prevention efforts, with particular attention to carbapenem resistance.

AIM: To investigate the efficacy and safety of dexamethasone versus conbercept in the treatment of diabetic macular edema(DME)with different optical coherence tomography(OCT)subtypes.METHODS: A total of 160 DME patients(160 eyes)admitted to our hospital from January 2021 to March 2023 were prospectively selected, and the patients were randomly divided into dexamethasone intravitreal implant group and conbercept group, with 80 cases(80 eyes)in each group, and DME patients were divided into 51 eyes with serous retinal detachment(SRD), 55 eyes with cystoid macular edema(CME), and 54 eyes with diffuse retinal thickening(DRT)according to OCT characteristics. The best corrected visual acuity(BCVA), central macular thickness(CMT), intraocular pressure and adverse reactions were compared before treatment and at 2, 3 and 6 mo postoperatively.RESULTS: There were differences in BCVA, CMT and intraocular pressure between the two groups at 2, 3 and 6 mo compared with those before operation(all P<0.05). There were differences in BCVA, CMT and intraocular pressure between the dexamethasone intravitreal implant group and the conbercept group in the treatment of patients with different types of DME(all P<0.05). The BCVA of patients with DRT and SRD types in the dexamethasone intravitreal implant group was improved at 3 and 6 mo after treatment compared with that in the conbercept group(all P<0.05). At 6 mo after treatment, the CMT of patients with DRT type in the dexamethasone intravitreal implant group was lower than that in the conbercept group(P<0.05). During the follow-up period, none of the patients experienced adverse events such as cataract exacerbation or retinal detachment.CONCLUSION: Both dexamethasone intravitreal implant and conbercept treatment can improve visual function and macular retinal morphology in patients with different OCT subtypes of DME with good safety, but the dexamethasone intravitreal implant is better than conbercept in the treatment of DRT type.

Objective:To analyze the pangenome, pan drug resistance genes, pan virulence genes, pan replicons, and others of the plasmids carried by hypervirulent Klebsiella pneumoniae (hvKP) in the world and their evolutionary trends over time, and provide evidence for more comprehensive understanding of the evolution of genetic diversity, drug resistance genes, and virulence genes of the plasmids. Methods:From the National Center for Biotechnology Information database, a total 1 738 plasmids were screened from 524 strains with completed genome sequences in 2 136 strains of hvKP carrying plasmids. Through pangenome, pan drug resistance gene, and pan-virulence gene composition and functional analyses, the curves of pangenome size and new gene size against plasmid isolation time were established, revealing the diversity of the plasmid pangenome and its evolutionary patterns.Results:The homologous genes, homologous drug resistance genes, homologous virulence genes, and replicons of the plasmids carried by hvKP comprised of 12 906, 149, 107 and 89 types, respectively. The fitting curves for the number of new genes, new drug resistance genes and new replicons increased with the increase of plasmids in an open state, while the curve for novel virulence genes was in a closed state. A obvious increase in new drug resistance genes was observed during 2018-2019. Among the newly added drug resistance genes during 2021-2023, beside those conferring aminoglycoside resistance, they were mainly new subtypes conferring carbapenem resistance.Conclusions:The pangenome of plasmids carried by hvKP exhibited high diversity, with the plasmid pan genes, pan drug resistance genes, and pan replicon types gradually expanding, while the pan virulence genes remains stable. The increase in novel drug resistance genes in specific years and the emergence of new carbapenem-resistant gene subtypes during 2021-2023 suggested the need for strengthened drug resistance surveillance and prevention efforts, with particular attention to carbapenem resistance.

Objective:Evaluation of the effectiveness of domestic ultrapulsed thulium laser ablation of isolated porcine kidneys.Methods:Forty-two fresh porcine kidneys were taken. One porcine kidney was dissected along the sagittal plane at the renal hilum, and then dissected along the coronal plane and divided into four pieces.A total of 168 pieces of renal tissues were obtained, of which 162 pieces were selected for the domestic hyperpulsed thulium laser ablation of isolated porcine kidneys using the single-needle method and the double-needle method, respectively. The ablation was carried out with different ablation modes (single-needle and double-needle methods), ablation power (4, 5, and 6 W), ablation modes (continuous, low-energy and high-frequency mode, and high-energy and low-frequency mode), and ablation time (10, 15, and 20 s). The size of the ablation area in terms of the long diameter, the short diameter, and the thick diameter were measured and recorded. The embedded tissues were sectioned and stained with HE to study the microscopic pathological characteristics of the ablation foci. The ablation foci volume and sphericity coefficient (Φ) were calculated, and the ablation foci volume and sphericity coefficient were statistically analyzed by analytic factorial design and one-way ANOVA.Results:The gross specimen showed that the single-needle ablation foci were elliptical in shape, containing black carbonized areas and gray-white necrotic areas with clear boundaries, and the peripheral renal tissues were pink, and the ablation focus was clearly demarcated from the normal tissues. The double-needle ablation foci were a large ellipse containing two small ellipse ablation foci, and the structure was similar to that of the single-needle method. Under the light microscope, the center of the ablation focus was a "cavity-like" carbonized area, outside of which was an area of coagulation necrosis, with deepened cell staining, reduced cell volume, disorganized arrangement, loose nuclei, nuclear consolidation, and some cell nuclei were cleaved and ablated. Ablation mode ( P<0.001), ablation pattern ( P <0.001), ablation time ( P <0.001), and ablation power ( P <0.001) all significantly affected ablation focus volume. The volume of the ablation foci increased with increasing number of needle feeds, longer ablation time, higher ablation power, and with the ablation mode being continuous mode. Single-needle ablation produced the largest volume of ablation foci (259.56 mm 3) in continuous mode, ablation time of 20 s, and ablation power of 6 W. Double-needle ablation produced the largest volume of ablation foci (452.00 mm 3) in continuous mode, ablation time of 20 s, and ablation power of 6 W. The analysis of the sphericity coefficient showed that in single-needle ablation, the sphericity coefficient was the largest (Φ=0.76) under the conditions of continuous mode, ablation power of 4 W, and ablation time of 15 s. The sphericity coefficient was the smallest (Φ=0.56) under the conditions of high-energy, low-frequency mode, ablation time of 10 s, and ablation power of 6 W, and the morphology of the ablation foci were more close to ellipsoid shape. When ablated by the double-needle method, the ablation foci morphology was closer to spherical shape (Φ=0.91) under the conditions of continuous mode, ablation time of 10 s, and ablation power of 5 W. The combined main effect and interaction results showed that ablation mode ( P<0.001), ablation pattern ( P<0.001), and ablation power ( P<0.001) significantly affected the sphericity coefficient of the ablation foci, and ablation time did not affect the ablation foci morphology. Conclusions:Domestic ultrapulsed thulium laser ablates isolated porcine kidney tissues with precise effect, the tissue morphology of the unablated area is normal, the thulium laser ablated foci have a definite safe boundary. Choosing double needle method, continuous mode, ablation power 6 W for 20 s, can ablate spherical cancer foci within 1 cm in diameter, which can be used for spherical small kidney cancer ablation. Selecting the single-needle method, high-frequency, low-energy mode and ablation power of 6 W, the ablation foci were similar to the oval volume, and could be used for the ablation of oval small renal cancer. However, this study is only limited to the animal ex vivo model, which needs to be confirmed by further study.

Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epige-netic mark in cancer, its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive pri-mary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors. In contrast, the TET protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1 associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkers to predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.

Purpose: C-X-C motif chemokine receptor 4 (CXCR4) and integrin αvβ6 play important roles in the malignant progression of multiple cancers. However, it remains unclear whether the expression of one or both proteins in breast cancer (BC) is of clinical significance. In this study, we investigated the expression of CXCR4 and integrin αvβ6 in BC tissues and their correlation with clinicopathological characteristics, including survival. Methods: CXCR4 and αvβ6 expression in 111 BC tissues was examined by immunocytochemistry. Correlations between the expression of the 2 proteins and patient clinicopathological characteristic were investigated using the Kaplan–Meier method and the Cox proportional hazards model. Results: CXCR4 and αvβ6 were overexpressed in BC tissue compared with normal breast tissue. Overexpression of both molecules was related to lymph node status (p = 0.013 and p = 0.022, respectively). αvβ6 overexpression was also associated with tumor size (p = 0.044). A positive correlation was detected between the expression of CXCR4 and αvβ6 (r = 0.649, p = 0.001), and co-overexpression of both molecules was associated with tumor size (p = 0.018) and lymph node metastasis (p = 0.015). Kaplan–Meier analysis revealed that overexpression of CXCR4, αvβ6, or both molecules was associated with short overall survival (OS; p < 0.001, p < 0.001, and p = 0.009, respectively) and disease-free survival (DFS; p < 0.001, p = 0.005, and p = 0.019, respectively). Multivariate analysis indicated that lymph node metastasis was an independent prognostic factor for unfavorable OS and DFS (p = 0.002 and p = 0.005, respectively), whereas co-overexpression of CXCR4 and αvβ6 was an independent prognostic factor only for OS (p = 0.043). Conclusion CXCR4 and αvβ6 may play synergistic roles in the progression of BC, and co-targeting of CXCR4 and αvβ6 could be a potential strategy for the prevention and treatment of BC.

Objective To investigate the experiences in observation and nursing care during perioperative period of cavernous sinus dural arteriovenous fistulas(DAVFS) embolized with coil and ONYX glue. Methods In the course of the operation,17 cases of cavernous sinus DAVFS were treated with psychological nursing, perioperation disease observation and complications preventive nursing. Results All patients with DAVFS could be embolized successfully using interventional techniques and without complications. Conclusions The therapeutic method of embolizing cavernous sinus DAVFS with coil and ONYX glue is secure and cost-effective.The key steps of the patients convalescence lie in comprehensive perioperative nursing,observing symptoms carefully and preventing complications.

Objective To evaluate the feasibility and safety of a delivery pathway for the performance of percutaneous left atrial appendage (LAA) occlusion in experimental canine models. Methods Transseptal puncture was performed via femoral vein approach under fluoroscopic and angiographic guidance in 12 experimental dogs. A pigtail catheter was advanced into the left atrium (LA), which was followed by LA angiography. The diameters of the neck of LAA were measured on LAA angiogram obtained in appropriate projection. After the delivery sheath was advanced along the wire into LA, a pigtail catheter was inserted into the ostium of the LAA and the sheath was then advanced over the pigtail into the LAA. LAA angiography was then performed through the delivery sheath to confirm the position of the delivery sheath. One hour after the procedure both electrocardiography (ECG) and transthoracic echocardiography (TTE) were carried out in five dogs to check the results, immediately after which the five dogs were sacrificed to macroscopically observe the damages of the puncture site of inter-atrial septum as well as inside the LA and LAA. One hour and 2 weeks after the procedure TTE was conducted in the remaining 7 dogs and these dogs were followed up for one month. Results One dog died of pericardial tamponade during the operation. In 8 dogs the LAA was clearly displayed in the projection position of right anterior oblique (RAO) 30°/cranial (CRA) 20°,while in 3 dogs the LAA was well visualized in the projection position of RAO 30° , and in one dog in the projection position of RAO 30°/caudal (CAU) 20°. The diameter of LAA neck was (13.6 ± 5.2) mm. The delivery sheath was safely advanced into the LAA along the pigtail catheter in all dogs, and no air embolism, thrombus or pericardial tamponade occurred. Hematoma at puncture point of groin occurred in 2 dogs, which was absorbed through pressure dressing. Macroscopic examination of the heart performed immediately after the operation showed that no bloody pericardial effusion was found, and mild hematoma at posterior wall of LA was seen in one dog and mild damage of the upper-margin intima of LAA was noted in 2 dogs. The mean fluoroscopy time was (10.1 ± 2.5) minutes and the mean operation time was (58 ± 12) minutes. TEE showed no pericardial effusion 2 weeks after the procedure. During the follow-up period of one month no sudden death, stroke or infection occurred. Conclusion This method of placing the delivery sheath into the LAA is clinically safe and effective, and it can reliably establish a pathway to advance the LAA occluder into LAA.