Objective To design and fabricate an integrated optoelectrical fiber to enable the simultaneous transmission of high-power laser and electrical current, thereby developing a novel tool for urological surgery.Methods A miniature metal sleeve was installed at the front end of a medical high-energy optical fiber, and corresponding conductive circuits were configured. The fiber was connected to a fiber thulium laser and a bipolar plasma generator simultaneously. Experiments of simulated vaporization were conducted on ex vivo porcine kidney tissues using thulium laser (50 W), plasma (100 W), and thulium laser + plasma (50 W+100 W), respectively. Tissue removal efficiency was calculated using the weighing method:tissue clearance rate (g/min)=[mass before vaporization (g) - mass after vaporization (g)]/vaporization time (min). Lateral tissue thermal damage was assessed with hematoxylin-eosin (HE) staining. One-way analysis of variance and least significant difference test were used for statistical analysis.Results The integrated optoelectrical fiber was successfully constructed, which could simultaneously and continuously transmit thulium laser and plasma electrocision current. The tissue clearance rate of the thulium laser+plasma group was significantly higher than that of the thulium laser group and plasma group [(0.49±0.13) g/min vs. (0.14±0.02) g/min vs. (0.11±0.04) g/min, P＜0.001]. The average lateral thermal damage depth of the thulium laser + plasma group showed no statistically significant difference compared to the thulium laser group [(985.5±178.5) μm vs.(957.5±197.4) μm, P＞0.05], but both were significantly higher than that of the simple plasma group [(499.6±78.0) μm] (P＜0.001). Conclusion The thulium laser + plasma energy transmitted simultaneously by the integrated optoelectrical fiber can vaporize kidney tissue more efficiently without additional thermal damage.

ObjectiveTo evaluate the predictive value of six surrogate indices of insulin resistance （IR） for cardiovascular disease （CVD） risk in adults with cardiovascular-kidney-metabolic syndrome （CKM） stages 0-3. MethodsRelated data of 6 813 participants from the China health and retirement longitudinal study （CHARLS） were analyzed. Cox proportional hazards models and restricted cubic spline （RCS） analyses were performed to evaluate the associations between six insulin resistance surrogate indices （TyG， TyG-BMI， TyG-WC， TyG-WHtR， TyG-CVAI， CVAI） and CVD incidence. Predictive performance of 6 indices was comprehensively compared from 3 dimensionalities， using receiver operating characteristic （ROC） curves for discriminative ability， net reclassification improvement （NRI） for incremental predictive value， and decision curve analysis （DCA） for clinical utility. ResultsAll six IR surrogate indices significantly predicted CVD in the CKM population. RCS analysis revealed linear associations between each index and CVD incidence. ROC analysis showed that CVAI had the highest AUC （0.628，95%CI： 0.611-0.646）， significantly outperforming the single TyG index （P=0.001 6）. NRI analysis indicated significant reclassification improvement for the event group with CVAI （event NRI=0.042 8）. DCA demonstrated that CVAI achieved the highest net benefit across most thresholds. Subgroup analysis confirmed stronger associations between CVAI and CVD risk in CKM stages 2-3. ConclusionsThese six IR surrogate indices serve as valuable tools for predicting CVD incidence in individuals with CKM stages 0-3. Among them， CVAI exhibits optimal predictive value for future CVD risk in adults with CKM stages 1-3.

Objective:To summarize the clinicopathological features, evolving trends in treatment and surgical approaches, and survival outcomes of patients who underwent D2 radical gastrectomy for gastric cancer in Shanxi Provincial Cancer Hospital over the past 11 years with the goal of providing a reference for the clinical practice of gastric cancer in this region.Methods:A retrospective observational study was conducted to analyze the clinicopathological data of patients who underwent D2 radical gastrectomy for pathologically confirmed gastric malignancy at the Department of Gastrointestinal Surgery, Shanxi Provincial Cancer Hospital from January, 2013 to December, 2023. Exclusion criteria consisted of: (1) residual gastric cancer or recurrent gastric cancer after surgery; (2) emergency gastric cancer resection due to bleeding, perforation, obstruction, or other causes; (3) comorbidity with other primary malignant tumors; (4) severe preoperative cardiopulmonary insufficiency or hepatic and renal insufficiency who cannot tolerate radical surgery; and (5) inconsistent main diagnosis information across the medical record system, pathological system, and gastric cancer-specific database. Patients were divided into three groups based on treatment methods: the surgery-only group, the perioperative chemotherapy group, and the adjuvant chemotherapy group. Endpoints included: (1) baseline patient characteristics; (2) trends in tumor location and pathological features; (3) evolution of treatment modalities; and (4) survival outcomes.Results:A total of 15,644 patients were included in the analysis, with 12,591 males and 3,053 females, the male-to-female gender ration was approximately 4∶1; the mean age was (61.2±9.5) years. The tumor sites were mainly concentrated in the esophagogastric junction (EGJ) (57.4%), followed by the antrum (25.9%). The incidence of EGJ cancer initially rose and then declined. However, gastric antrum tumors remained stable, and gastric body tumors showed a slow upward trend after 2020, accounting for 16.7%. In terms of pathological types, poorly differentiated carcinoma was the most prevalent, accounting for 55.9%, followed by moderately differentiated carcinoma (24.2%), mucinous adenocarcinoma (or signet ring cell carcinoma,14.1%), neuroendocrine carcinoma (4.8%), and well-differentiated carcinoma (0.9%). The proportion of poorly differentiated adenocarcinoma showed a significant upward trend overall as well, peaking at 65.6% in 2022 and decreasing to 57.5% in 2023. Mucinous adenocarcinoma (or signet ring cell carcinoma) exhibited fluctuations with a first increase followed by a decrease: it peaked at 17.3% in 2018, dropped sharply to 8.4% in 2022, and rose back to 13.8% in 2023. The proportions of well-differentiated adenocarcinoma, moderately differentiated adenocarcinoma, and neuroendocrine tumors remained stable year by year. In terms of pathological staging, the overall proportions of gastric cancer at Stage 0, Stage I, Stage II, Stage III, and Stage IVa were 0.5%, 17.3%, 25.1%, 54.9%, and 2.3%, respectively. For Stage III, its proportion was 74.6% in 2013, which decreased to 46.4% by 2023. Stages I and II gastric cancer showed an upward trend, with their proportions rising from 10.2% and 12.1% in 2013 to nearly 21.0% and 29.6% in 2023, respectively. Between 2013 and 2023, the proportion of patients who received surgery alone continued to decrease, with this proportion dropping to 34.7% in 2023. In contrast, the number of patients who received adjuvant chemotherapy increased year by year, reaching 54.2% in 2023. Since 2017, the application of perioperative chemotherapy has gradually increased, rising to 11.1% in 2023. Immunotherapy showed an almost synchronous growth trend with perioperative chemotherapy. However, targeted therapy exhibited a downward trend after a period of growth. There were 10,704 cases of open surgery (68.4%), 4,744 cases of laparoscopic surgery (30.3%), and 193 cases of transthoracic surgery (1.2%). Pathological margin positivity was observed in 443 cases (2.8%), and the volume of gastric cancer surgeries gradually increased, peaked in 2021 before subsequently decreasing gradually. However, the volume of laparoscopic surgeries did not decrease; instead, it showed an upward trend. The main resection method for EGJ tumors was total gastrectomy, accounting for 78.5% of the total, followed by proximal gastrectomy, which accounted for 21.5%. After total gastrectomy, esophagojejunal Roux-en-Y anastomosis was the primary anastomotic method, and for proximal gastrectomy, the main anastomotic method was esophagogastric anastomosis, which accounted for 68.0% of the total. For distal gastrectomy, Billroth II anastomosis was the most common anastomotic technique, accounting for 92.7% of these procedures. The overall incidence of postoperative complications was 14.5% (2,264/15,644), among which the incidence of severe complications (grades III-IV) was 4.5% (706/15,644). The entire cohort was followed up with for (47.1±36.8) months, and the 1-year, 3-year, and 5-year overall survival rates were 86.4%, 65.9%, and 58.1%, respectively. For patients with stage 0, I, II, III, and IV gastric adenocarcinoma, the 1-year overall survival rates were 95.7%, 98.0%, 89.4%, 81.0%, and 49.1%, respectively; the 3-year overall survival rates were 92.1%, 94.6%, 81.9%, 51.4%, and 14.7%, respectively; and the 5-year overall survival rates were 89.4%, 91.7%, 75.1%, 41.5%, and 10.0%, respectively. For patients with stage I, II, III, and IV gastric neuroendocrine carcinoma, the 1-year overall survival rates were 96.7%, 91.1%, 73.8%, and 52.6%, respectively; the 3-year overall survival rates were 87.2%, 69.6%, 46.1%, and 32.1%, respectively; and the 5-year overall survival rates were 87.2%, 62.2%, 36.7%, and 32.1%, respectively.Conclusions:Gastric cancer in Shanxi Province is characterized by a male predominance, a high prevalence of tumors at the esophagogastric junction, a large proportion of poorly differentiated adenocarcinoma, and presentation at advanced stages (predominantly Stage III). The detection rate of early gastric cancer has been increasing year by year, the volume of laparoscopic surgeries has been on the rise annually, and the treatment model has shifted from single surgery to comprehensive treatment.

Danggui Buxue decoction(DBD)is a classic prescription with immunomodulatory and hematopoietic effects.Previous studies have shown the DBD has potential to be used as an oral im-mune booster.However,its immunomodulatory effects and mechanism of action have not been thoroughly studied,especially the protective mechanism of immunomodulatory regulation in the state of immunosuppressive is still unclear.The aim of this study was to explore the protective mechanism of DBD in the immunosuppressive state using network pharmacology combined with animal experiments verification.The active components,core targets and signaling pathways of DBD in treating immunosuppression were obtained using network pharmacology tools.On this ba-sis,the active components of DBD were identified using HPLC-MS,and in vivo studies were con-ducted at the same time.The key active components of DBD obtained using network pharmacology included quercetin,kaempferol and formononetin.The core targets included TP53,RELA,TNF,AKT1,and IL-6.KEGG pathway enrichment analysis showed that phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT)may play an important role in the treatment of immunosuppres-sive diseases using DBD.Molecular docking confirmed that each core target had good binding activ-ity with its corresponding compounds.Animal experiments showed that after DBD intervention,the mRNA gene and protein expression of RELA,TNF,and IL-6 in the serum was significantly down-regulated.The mRNA expression of PI3K and AKT in the ileum and PI3K protein expression were also downregulated.In conclusion,DBD exerts its role in treating immunosuppressive diseases by regulating the PI3K-AKT signaling pathway.

To assess the implantation effectiveness of porous scaffolds, it is essential to consider not only their mechanical properties but also their biological performance. Given the high cost, long duration and low reproducibility of biological experiments, simulation studies as a virtual alternative, have become a widely adopted and efficient evaluation method. In this study, based on the secondary development environment of finite element analysis software, the strain energy density growth criterion for bone tissue was introduced to simulate and analyze the cell proliferation-promoting effects of four different lattice porous scaffolds under cyclic compressive loading. The biological performance of these scaffolds was evaluated accordingly. The computational results indicated that in the early stages of bone growth, the differences in bone tissue formation among the scaffold groups were not significant. However, as bone growth progressed, the scaffold with a porosity of 70% and a pore size of 900 μm demonstrated markedly superior bone formation compared to other porosity groups and pore size groups. These results suggested that the scaffold with a porosity of 70% and a pore size of 900 μm was most conducive to bone tissue growth and could be regarded as the optimal structural parameter for bone repair scaffold. In conclusion, this study used a visualized simulation approach to pre-evaluate the osteogenic potential of porous scaffolds, aiming to provide reliable data support for the optimized design and clinical application of implantable scaffolds.
Tissue Scaffolds/chemistry* ; Porosity ; Finite Element Analysis ; Tissue Engineering/methods* ; Computer Simulation ; Bone Development ; Osteogenesis ; Humans ; Cell Proliferation

Objective:To investigate the difference in intracranial infection rate between long-tunneled external ventricular drainage(LTEVD)and conventional external ventricular drainage(EVD),as well as the risk factors for intracranial infection.Methods:A retro-spective analysis was performed for the clinical data of 45 patients who were admitted to Department of Neurology Center,The Third Affiliated Hospital of Chongqing Medical University,from January 2020 to December 2022 and underwent EVD,among whom 13 patients underwent LTEVD(LTEVD group)and 32 patients underwent conventional EVD(EVD group).Related data were recorded for both groups,including general information,postoperative catheter-related complications,and postoperative management,to investi-gate the effect on reducing the rate of intracranial infection.According to the presence or absence of intracranial infection after surgery,the patients were divided into the infection group with 10 patients and non-infection group with 35 patients,and related clini-cal data were analyzed to investigate the risk factors for intracranial infection.Results:The LTEVD group had a significantly lower secondary infection rate of catheterization days than the EVD group[2.40‰(1/417)vs.27.19‰(9/331),P=0.009].The duration of catheterization was 14-85 days[27.00(22.50,36.50)days]in the LTEVD group and 8-22 days[9.00(8.00,11.50)days]in the EVD group,suggesting that the LTEVD group had a significantly longer duration of catheterization than the EVD group(P=0.000).The multivariate logistic regression analysis showed that the times of cerebrospinal fluid sampling was an independent risk factor for post-operative intracranial infection in patients undergoing EVD,and the use of LTEVD was a protective factor against intracranial infection after EVD.Conclusion:Compared with conventional EVD,LTEVD can safely prolong the duration of catheterization and reduce the rate of postoperative intracranial infection in patients undergoing EVD.The use of LTEVD procedure and the reduction in the times of cerebrospinal fluid sampling can reduce the risk of postoperative in-tracranial infection.

Objective To explore the interaction between long non-coding RNA growth arrest-specific 5(GAS5)and miR-135b-5p/adenomatous polyposis coli(APC)axis,and to elucidate its biological function in the proliferation,metastasis and invasion of glioma.Methods The relationship of GAS5 expression level with survival rate of glioma patients was analyzed based on CGGA database.qRT-PCR was used to detect the expression level of GAS5 in glioma tissues and cell lines.Human glioma T98 and A172 cell lines were subjected for overexpression and knockdown of GAS5,miR-135b-5p and APC by transfection.Western blotting and qRT-PCR were applied to measure the expression of related genes in glioma tissues or cell lines.CCK-8,Transwell and wound healing assays was conducted to determine the effect of GAS5 on the viability and motility of glioma cells.Moreover,dual luciferase reporter analysis were utilized to elucidate the regulatory mechanisms of GAS5 and miR-135b-5p/APC.Results Analysis on CGGA database showed that the survival rate of glioma patients with low GAS5 expression was significantly decreased(P＜0.001).Western blotting and qRT-PCR indicated that GAS5 was down-regulated in the glioma cell lines and tissues than human normal astrocytes and para-cancer tissues(P＜0.01).The results of CCK-8,Transwell and wound healing assays revealed that overexpression of GAS5 significantly inhibited the viability,invasion and migration abilities in T98 cells when compared with the cells of the vector group(P＜0.01).Dual luciferase reporter analysis displayed that there were binding sites between GAS5 and miR-135b-5p,and the expression of the two was negatively correlated(P=0.019).Further studies suggested that the effect of GAS5 on biological function in glioma cells was through targeting miR-135b-5p,and overexpression of APC reversed the promoting effect of miR-135b-5p on glioma cells(P＜0.01).Western blotting displayed that enhancing miR-135b-5p expression inhibited the expression of APC(P＜0.001),and GAS5 upregulated the expression of APC by targeting miR-135b-5p(P＜0.01).Conclusion GAS5 inhibits the progression of glioma via miR-135b-5p/APC axis,which revealing the molecular regulatory mechanism of GAS5/miR-135b-5p/APC.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*