Chemotherapeutic drugs generally lack specificity, and so the development of a carrier that can actively target delivery of chemotherapy drugs without immunogenicity to organisms has attracted increasing attention. In this work, a multivalent aptamer (Multi-Apt) was constructed by hybridizing a long single-stranded DNA (ssDNA) with tandem repeated sequences synthesized by rolling circle amplification (RCA) with several ssDNA encoding aptamer AS1411 sequences. The double-helix structure was used to load the anti-tumor drug doxorubicin (Dox) for targeted treatment of B16 cells. The binding ratio of RCA product to ssDNA was optimized by agarose gel electrophoresis, and the loading and release of Dox were explored using a microplate reader. The targeting and growth inhibition of Multi-Apt-Dox on B16 cells were investigated by fluorescence microscopy, flow cytometry, microplate reader, CCK-8 assay and wound healing assay. The results showed that the optimal molar ratio of RCA product to ssDNA was 1:50. Fluorescence microscopic pictures, flow cytometry analysis and microplate reader experimental results showed that each Multi-Apt could load approximately 200 Dox molecules, and the affinity of Multi-Apt for B16 cells was 46-fold higher than that of free AS1411. Cell experimental results demonstrated that Multi-Apt induced selective cytotoxicity after intracellular degradation and drug release, thereby greatly reducing the adverse reactions of Dox to normal cells and providing a new strategy for targeted drug delivery in tumor treatment.

By analyzing the current application of multi-modal data in the diagnosis of gastric "inflammation-cancer" transformation， this study explored the feasibility and strategies for constructing a disease-syndrome integrated diagnosis and treatment system. Based on traditional Chinese medicine （TCM） phenomics， we proposed utilizing multi-modal data from literature research， cross-sectional studies， and cohort follow-ups， combined with artificial intelligence technology， to establish a multi-dimensional diagnostic and treatment index system. This approach aims to uncover the complex pathogenesis and transformation patterns of gastric "inflammation-cancer" progression. Additionally， by dynamically collecting TCM four-diagnostic information and modern medical diagnostic information through a long-term follow-up system， we developed three major modules including information extraction， multi-modal phenotypic modeling， and information output， to make it enable real-world clinical data-driven long-term follow-up and treatment of chronic atrophic gastritis. This system can provide technical support for clinical diagnosis， treatment evaluation， and research， while also offering insights and methods for intelligent TCM diagnosis.

Background: s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer. Methods: We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R. Results: Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices. Conclusions SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.

Background: s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer. Methods: We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R. Results: Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices. Conclusions SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.

Background: s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer. Methods: We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R. Results: Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices. Conclusions SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.

BACKGROUND:Exercise has been widely recognized in the prevention and treatment of diabetes.Aerobic exercise has become an important part of the treatment of type 1 diabetes.However,the effect of treadmill exercise on the metabolism and chronic neuroinflammation of type 1 diabetes in different sexes needs further discussion. OBJECTIVE:To study the effects of treadmill exercise on metabolism and chronic neuroinflammation in type 1 diabetes mice of different sexes. METHODS:Forty C57BL/6 mice were divided into male group and female group,with 20 mice in each group.Then,a diabetes model was established by continuous injection of streptozotocin at 80 mg/kg for 3 days.Ten rats from each group were randomly selected to perform 6-week treadmill exercise as the diabetes+exercise group and another 10 rats from each group were selected as the diabetes group.Serum sex hormones,liver tissue oxidative stress,brain tissue inflammatory factors,and liver pathology were detected,and Morris water maze was performed for the observation of behavioral changes in mice. RESULTS AND CONCLUSION:Compared with the diabetes group,the diabetes+exercise group delayed the rise of blood sugar in type 1 diabetes mice(P＜0.05)and showed a significant reduction in serum follicle-stimulating hormone,luteinizing hormone,liver superoxide dismutase,malondialdehyde,brain tumor necrosis factor α,interleukin-6 and interleukin-1β levels(P＜0.01),while serum estradiol,progesterone,estrogen,and liver glutathione peroxidase protein levels were significantly increased(P＜0.01,P＜0.05).Compared with male type 1 diabetes mice,female type 1 diabetes mice had significantly higher estradiol levels and lower luteinizing hormone levels(P＜0.05).Compared with the male diabetes+exercise group,the female diabetes+exercise group had lower liver glutathione peroxidase levels(P＜0.05).Compared with type 1 diabetes mice,the escape latency of exercise training mice was shorter(P＜0.01).In male mice,exercises significantly increased the time and platform crossing times of type 1 diabetes mice in the target quadrant(P＜0.01 or P＜0.05),while in female mice,exercises significantly increased the time of type 1 diabetes mice in the target quadrant(P＜0.05).Correlation analysis results showed that the levels of follicle-stimulating hormone,luteinizing hormone,progesterone,superoxide dismutase,malondialdehyde,tumor necrosis factor α,and interleukin-6 were positively correlated with the level of interleukin-1β(P＜0.05 or P＜0.01),whereas the levels of estradiol and progesterone were negatively correlated with the levels of superoxide dismutase,malondialdehyde,tumor necrosis factor α,interleukin-6 and interleukin-1β(P＜0.05 or P＜0.01).Overall,there are sex differences in the effects of treadmill exercise on metabolic indicators and chronic neuroinflammatory regulation in diabetes mice.Sex hormones are an important variable of treadmill exercise in the metabolic,inflammatory and cognitive responses in diabetes mice.

In patients with acute ischemic stroke, there is a wide variation in the composition of blood clots that block the blood vessels. Some imaging features are associated with the components of the clot, such as thrombus permeability, which is related to higher red blood cell density and lower fibrinogen density. The different components and mechanical properties of the clot may have an impact on treatment effectiveness and risk. Therefore, this article aims to summarize the correlation between thrombus permeability and biological, imaging characteristics, and explore the clinical significance of thrombus permeability in the treatment of patients with acute ischemic stroke, providing reference and assistance for neurologists.

OBJECTIVE To evaluate the effictiveness and safety of recombinant human endostatin combined with afatinib and teggio in the treatment of advanced lung squamous cell carcinoma. METHODS A total of 25 patients with driver-negative advanced lung squamous cell carcinoma were included in this single-arm prospective study, and the enrolled patients were treated with recombinant human endostatin combined with afatinib and teggio as scheduled. Progression-free survival(PFS), overall survival(OS), disease control rate(DCR), objective response rate(ORR), and adverse reactions(AR) were observed and analyzed. RESULTS The 25 enrolled patients received at least 2 cycles of second-line treatment, and were followed up as of March 31, 2023. Among them, 4 patients had partial remission, 17 patients had stable disease, and 4 patients experienced progressive disease. The ORR confirmed by the researchers was 16%(95%CI, 4.5%−36.1%), DCR was 84%(95%CI, 63.9%−95.5%), and median PFS was 5.3 months(95%CI, 3.5−6.9 months). The median OS had not yet been achieved. The entire group of patients had good treatment tolerance, and the most common level Ⅲ or Ⅳ adverse events related to treatment were leukopenia(20%) and rash(12%), with no reported treatment-related deaths. CONCLUSION Recombinant human endostatin combined with afatinib and teggio in the second line treatment of advanced lung squamous cell carcinoma can prolong the progression free survival period of patients and is relatively safe, which is worth further exploration and promotion.

High-quality development of digital health industry is an important symbol of realizing a healthy and digital China,and it is a new economic growth point.Using literature and other research methods,it comprehensively explores the theoretical logic,practical bottlenecks and solutions to the high-quality development of digital health industry driven by new quality productivity.It concludes that the new quality productivity can promote the high-quality development of digital health industry by strengthening the effect of institutional innovation,creating a good development environment for the industry;strengthening the effect of structural optimization,driving the upgrading of the industry;strengthening the effect of strengthening and complementing the chain,prolonging the industrial value chain;strengthening the effect of organizational remodeling,improving the industrial organizational system;and strengthening the effect of factor enhancement,fostering the high-end innovation factors.Aiming at the bottlenecks of unsound institutional mechanism,deep structural traps,low-end locking of the value chain,weak integration capacity of health organizations,and insufficient allocation of innovative elements,proposing to promote the deep integration of new elements and resources,and to accumulate the kinetic energy of innovation and development of the digital health industry;strengthening the status of digital health enterprise as the main body of innovation,and to stimulate the vitality of health management organizations;vertically and horizontally integrating the digital health industry chain,and comprehensively excavating the value of the digital health industry;driving the digital health industry to change the new and new,rooting the foundation of digital health industry development;deepening the reform of the digital health management system and mechanism,and improving the system to ensure the relief of the system.

Objective:To investigate the effect of low-dose ketamine on neuroinflammation and microcirculation in mice with traumatic brain injury (TBI).Methods:Sixty adult male C57BL/6 mice, weighing 22-28 g, were randomly divided into sham-operated group, TBI group, Sham+ketamine group, and TBI+ketamine group ( n=15). A controlled cortical impingement (CCI) method was used to establish TBI models in the later 2 groups. Sham+ketamine group and TBI+ketamine group were intraperitoneally injected with 30 mg/kg ketamine once daily for 3 d at 30 min after TBI; sham-operated group and TBI group were intraperitoneally injected same amount of saline at the same time points. Cerebral cortical blood flow in 6 mice from each group was measured by laser speckle contrast imaging (LSCI) before, immediately after, 30 min after, 1 d after and 3 d after modeling, respectively. Three d after modeling, immunohistochemical staining and immunofluorescent double label staining were used to detect the nuclear translocation of microglia markers, ionized calcin-antibody-1 (Iba-1) and nuclear factor (NF)-κB p65 in damaged cortical brain tissues in 6 mice from each group. The remaining 3 mice in each group were sacrificed and tissue plasma was extracted 3 d after modeling; levels of NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB and inducible nitric oxide synthase (iNOS) in cortical brain tissues were detected by Western blotting. Expressions of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β) and interleukin-6 (IL-6), iNOS, reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cortical brain tissues were detected by ELISA. Results:LSCI indicated that, 3 d after modeling, relative blood flow in local cerebral microcirculation of TBI+ketamine group was significantly increased compared with that of TBI group ( P<0.05). Immunohistochemical staining indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased number of Iba-1 positive cells in the cerebral cortex ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased number of Iba-1 positive cells ( P<0.05). ELISA indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ ketamine group had significantly decreased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05). Immunofluorescent double label staining indicated obviously inhibited NF-κB p65 nuclear translocation in TBI+ketamine group when it was compared with TBI group. Western blotting indicated that compared with the sham-operated group and Sham+ketamine group, the TBI+ketamine group had significantly increased iNOS, NF-κB p65, p-NF-κB p65 and P-IκB protein expressions in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased protein expressions of iNOS, NF-κB p65, p-NF-κB p65 and p-IκB in damaged cortical brain tissues ( P<0.05). Conclusion:Low-dose ketamine reduces neuroinflammation and improves cerebral microcirculatory blood flow after open TBI, whose mechanism may be related to inhibition of microglia NF-κB/iNOS pathway.