Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood. Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages. Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages, and its intracellular concentration decreases in cells secreting TNF-α. This suggests that ADA2 may function as a lysosomal adenosine deaminase, regulating TNF-α expression by the cells. Interestingly, pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage (BAL), correlating with elevated pro-inflammatory cytokine levels. Conversely, cord blood has low ADA2 levels, creating a more immunosuppressive environment. Additionally, secreted ADA2 can bind to apoptotic cells, activating immune cells by reducing extracellular adenosine levels. These findings imply that ADA2 release from monocytes during inflammation, triggered by growth factors, may be crucial for cell activation. Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.
Humans ; Adenosine Deaminase/deficiency* ; Monocytes/cytology* ; Cell Differentiation ; Intercellular Signaling Peptides and Proteins/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Biomarkers/metabolism* ; Macrophages/metabolism* ; Pneumonia/metabolism*

Objective:To observe any effect of dual-task training on abnormal gait and fall risk among hemiplegic stroke survivors.Methods:A total of 90 stroke survivors were randomly divided into a control group, a cognitive dual-task group, and a motor dual-task group, each of 30. All 3 groups received conventional post-stroke medication and rehabilitation training, but the cognitive and motor dual-task groups received cognitive or motor dual-task training as well. Before and after 4 weeks of the training, everyone′s balance, walking and lower limb motor functioning were assessed using the Berg Balance Scale (BBS), the Timed Up and Go test (TUGT) and the Fugl-Meyer lower extremity assessment (FMA-LE). Additionally, three-dimensional gait analysis was performed to document gait speed, bilateral spatial asymmetry, bilateral temporal asymmetry, and the dual-task cost (DTC) of gait speed.Results:Significant improvement was observed in the average BBS scores, TUGT times, FMA-LE scores, gait speed, DTC of gait speed, bilateral spatial asymmetry ratios, and bilateral temporal asymmetry ratios of all 3 groups after the experiment. The averages of the cognitive dual-task group were then significantly better than the control group′s averages. The motor dual-task group′s average BBS score (42.67±7.87), TUGT time [(22.30±8.53)s], gait speed (0.58±0.2m/s), DTC of gait speed (19.02±5.99%), and bilateral spatial asymmetry ratio (19.79±10.41%) were then significantly better than the control group′s averages but not significantly different from those of the cognitive dual-task group.Conclusions:Dual-task training can significantly improve the balance, walking and lower limb motor function of stroke survivors, correcting their abnormal gait patterns and consequently reducing their fall risks.

Background Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants widely distributed in the environment. Epidemiological studies have shown that PFAS exposure is closely associated with liver dysfunction and an increased risk of liver cancer. Some animal and cell experiments have also revealed its hepatotoxicity and potential carcinogenicity; however, the related carcinogenic mechanism has not yet been fully elucidated. Objective To explore the potential molecular mechanism of PFAS-induced liver cancer, identify the key causal genes, and specifically evaluate the causal association and expression changes of KMT2C in this process, as well as the binding stability between KMT2C and PFAS, and to provid a theoretical basis for mechanistic studies and molecular target discovery in PFAS-related liver cancer. Methods Toxicity prediction was performed on six representative PFAS. Potential target genes of PFAS were identified by integrating results from SwissTargetPrediction, STITCH, and TargetNet databases. Liver cancer-related genes were retrieved from GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The intersection of PFAS targets and liver cancer-related genes was used to obtain core genes. A compound-gene-disease regulatory network was constructed, and a protein–protein interaction network was established using STRING database. A core gene network was visualized based on node degree values. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore biological functions and enriched signaling pathways. Subsequently, two-sample Mendelian randomization was employed to assess potential causal relationships between candidate genes and hepatocellular carcinoma, enabling the identification of key genes. Molecular docking analysis using AutoDock was conducted to evaluate the binding stability between KMT2C and PFAS, and TCGA data were used to validate the differential expression of KMT2C between hepatocellular carcinoma and adjacent normal tissues. Results PFAS exhibited multisystem toxicity and posed significant risks of liver injury and carcinogenesis. A total of 266 PFAS target genes and 2923 liver cancer-related genes were identified, with 61 intersecting genes obtained. The enrichment analysis revealed that these intersecting genes were primarily involved in epigenetic regulation, nuclear receptor signaling pathways, and apoptosis-related pathways including TGF-β FoxO and Notch, suggesting their roles in diverse tumor-related biological processes. The two-sample Mendelian randomization results showed a significant negative causal association between KMT2C and hepatocellular carcinoma (OR=0.68, P <0.05). The molecular docking results demonstrated that all tested PFAS exhibited favorable binding to the KMT2C protein, with binding energies below –5.0 kcal·mol⁻¹. KMT2C was significantly upregulated in hepatocellular carcinoma tissues (unpaired P=0.025; paired P=8.38 × 10⁻⁴). Conclusion The KMT2C protein is found to stably bind with all six PFAS, exhibiting strong structural affinity. A causal relationship is identified between KMT2C and the development of hepatocellular carcinoma. TCGA data indicate that KMT2C is significantly upregulated in hepatocellular carcinoma tissues, and it may serve as a key regulatory target in PFAS-related liver cancer.

Background and Aims:Whether to close mesenteric fissures during laparoscopic radical resection of colorectal cancer remains controversial.Traditional suture closure is technically demanding and may injure mesenteric vessels.This study aimed to evaluate the safety and efficacy of using α-cyanoacrylate medical glue to close mesenteric fissures during laparoscopic colorectal cancer surgery.Methods:A retrospective analysis was conducted on patients who underwent laparoscopic radical resection of colorectal cancer in the Department of Colorectal Surgery,the Sixth Affiliated Hospital of Sun Yat-sen University,from January 2022 to December 2023.Seventy-eight patients who received intraoperative α-cyanoacrylate glue closure of mesenteric fissures were included as the observation group,and 74 patients without fissure closure were selected as the control group using the propensity score matching method.Perioperative parameters,postoperative recovery,and complications were compared between the two groups.Results:No significant differences were observed in baseline characteristics or main intraoperative variables between groups(all P>0.05).The observation group had significantly less ascitic drainage within 3 days after operation[(203.14±116.44)mL vs.(384.53±243.89)mL,P<0.01]and shorter postoperative gas passage,defecation,and drainage tube removal times(all P<0.01).The incidence of postoperative complications and intestinal obstruction was comparable between groups(all P>0.05).Multivariate analysis showed that intraoperative application of α-cyanoacrylate glue was an independent promoting factor for intestinal exhaust within 3 days after surgery(OR=5.739,P=0.000).Conclusion:The use of α-cyanoacrylate medical glue for closing mesenteric fissures during laparoscopic radical resection of colorectal cancer is safe and feasible.It effectively reduces postoperative ascitic drainage and accelerates bowel recovery,offering a simple and reliable alternative to traditional suture closure.

Background and Aims:Whether to close mesenteric fissures during laparoscopic radical resection of colorectal cancer remains controversial.Traditional suture closure is technically demanding and may injure mesenteric vessels.This study aimed to evaluate the safety and efficacy of using α-cyanoacrylate medical glue to close mesenteric fissures during laparoscopic colorectal cancer surgery.Methods:A retrospective analysis was conducted on patients who underwent laparoscopic radical resection of colorectal cancer in the Department of Colorectal Surgery,the Sixth Affiliated Hospital of Sun Yat-sen University,from January 2022 to December 2023.Seventy-eight patients who received intraoperative α-cyanoacrylate glue closure of mesenteric fissures were included as the observation group,and 74 patients without fissure closure were selected as the control group using the propensity score matching method.Perioperative parameters,postoperative recovery,and complications were compared between the two groups.Results:No significant differences were observed in baseline characteristics or main intraoperative variables between groups(all P>0.05).The observation group had significantly less ascitic drainage within 3 days after operation[(203.14±116.44)mL vs.(384.53±243.89)mL,P<0.01]and shorter postoperative gas passage,defecation,and drainage tube removal times(all P<0.01).The incidence of postoperative complications and intestinal obstruction was comparable between groups(all P>0.05).Multivariate analysis showed that intraoperative application of α-cyanoacrylate glue was an independent promoting factor for intestinal exhaust within 3 days after surgery(OR=5.739,P=0.000).Conclusion:The use of α-cyanoacrylate medical glue for closing mesenteric fissures during laparoscopic radical resection of colorectal cancer is safe and feasible.It effectively reduces postoperative ascitic drainage and accelerates bowel recovery,offering a simple and reliable alternative to traditional suture closure.

Objective:To observe any effect of dual-task training on abnormal gait and fall risk among hemiplegic stroke survivors.Methods:A total of 90 stroke survivors were randomly divided into a control group, a cognitive dual-task group, and a motor dual-task group, each of 30. All 3 groups received conventional post-stroke medication and rehabilitation training, but the cognitive and motor dual-task groups received cognitive or motor dual-task training as well. Before and after 4 weeks of the training, everyone′s balance, walking and lower limb motor functioning were assessed using the Berg Balance Scale (BBS), the Timed Up and Go test (TUGT) and the Fugl-Meyer lower extremity assessment (FMA-LE). Additionally, three-dimensional gait analysis was performed to document gait speed, bilateral spatial asymmetry, bilateral temporal asymmetry, and the dual-task cost (DTC) of gait speed.Results:Significant improvement was observed in the average BBS scores, TUGT times, FMA-LE scores, gait speed, DTC of gait speed, bilateral spatial asymmetry ratios, and bilateral temporal asymmetry ratios of all 3 groups after the experiment. The averages of the cognitive dual-task group were then significantly better than the control group′s averages. The motor dual-task group′s average BBS score (42.67±7.87), TUGT time [(22.30±8.53)s], gait speed (0.58±0.2m/s), DTC of gait speed (19.02±5.99%), and bilateral spatial asymmetry ratio (19.79±10.41%) were then significantly better than the control group′s averages but not significantly different from those of the cognitive dual-task group.Conclusions:Dual-task training can significantly improve the balance, walking and lower limb motor function of stroke survivors, correcting their abnormal gait patterns and consequently reducing their fall risks.

Objective To analyze the confirmation results of initial screening positive for human immunodeficiency virus (HIV) antibodies and to investigate the rationality of the gray zone for the signal-to-cutoff (S/CO) ratio values obtained by chemiluminescence assay. Methods A total of 184 specimens with positive HIV antibody screening results were collected. Confirmation was conducted using the Western blot (WB) method and viral nucleic acid testing, and the confirmation outcomes and band distribution were observed. The receiver operating characteristic (ROC) curve was employed to predict the optimal cutoff value, and the rationality of S/CO values in establishing a gray zone for HIV antibody was analyzed. Results Among the 184 HIV antibody screening positive samples, 153(83.15%) were initially screened by chemiluminescence, and 31 (16.85%) were screened by colloidal gold method. Male cases (57.07%) and those aged 40 years or older (75.00%) had higher proportion of initial screening positivity than females and other age groups. Supplemental WB testing revealed that 101 (54.89%) cases were confirmed as HIV-1 antibody positive, 56(30.43%) were negative, and 27(14.67%) were indeterminate. Of the 27 indeterminate cases, one was confirmed positive by NAT (initial S/CO value by chemiluminescence5.60), while the remaining 26 were negative. The positive agreement rates between chemiluminescence, colloidal gold and supplemental WB testing were 65.36% and 3.23%, respectively, with statistically significant difference (χ²=40.191, P < 0.05). Among 27 cases with indeterminate HIV-1 antibody results, upon further nucleic acid testing for viral load, one case exhibited WB banding pattern of P24+gp160, and the nucleic acid load confirmed this case as positive. In the distribution of band patterns among indeterminate samples, P24 had the highest occurrence (74.07%), followed by P66 (11.11%), gp160 (7.41%) as well as P17 and gp41 (both 3.70%). The ROC curve predicted the optimal S/CO cutoff value to be 5.15, with an area under the curve (AUC) of 0.904, sensitivity and specificity of 83.30% and 76.40%, respectively, and 95%CI of 0.861 to 0.948. There was a good correlation between the WB band patterns and confirmation results for initial screening positive cases (P < 0.05), with the highest correlation found for the P24 band (r=0.910). Conclusion There is a certain rate of false positives among HIV antibody initial screening positive cases, and effective screening can be achieved through WB testing. Additionally, based on the current testing platform, the gray zone for HIV antibody S/CO values in the chemiluminescence assay is set at 1.00 to 5.15, which exhibits high sensitivity.

Objective:To observe the impact of core stability training in the sling exercise therapy pattern on the balance of stroke survivors.Methods:Sixty stroke survivors were randomly divided into a control group ( n=30) and an experimental group ( n=30). In addition to routine rehabilitation training, the control group received traditional core stability training, while the experimental group underwent core stability training applying the sling exercise therapy pattern. Before and after 4 weeks of training, the standing balance of both groups was evaluated using the Prokin balance trainer, with the length and area of motion recorded when performing the balance test with the eyes open and closed. Surface electromyography was used to record the average EMG (AEMG) values of the bilateral erector spinae and multifidus muscles during the balance testing. Results:After the 4 weeks of training the length and the area of progression of the center of the pressure were both significantly smaller for both groups than before the training with the eyes both open and closed. The average length and area in the experimental group were significantly less than among the controls. The AEMG values recorded during the balance tests were significantly higher than those before the intervention for both groups, with the multifidus muscle averages on the affected side significantly greater in the experimental group than among the controls when performing the balance test with the eyes closed.Conclusion:Core stability training in the sling exercise therapy pattern is superior to conventional core stability training because it can better improve the balance of stroke survivors.

Objective:To evaluate the effect of using a walking support band on the gait of stroke survivors.Methods:Sixty stroke survivors were randomly divided into a walking support band group ( n=20), an ankle foot orthosis (AFO) group ( n=20) and a conventional rehabilitation group ( n=20). All three groups received conventional rehabilitation therapy, while the AFO group members were additionally provided with an ankle-foot orthosis and the walking support band group members received training wearing a walking support band. Before and after 4 weeks of treatment, all three groups were evaluated using three-dimensional gait analysis. Results:A total of 57 patients finished the study. After the interventions, the average step speed, frequency and step length of the three groups had all increased significantly, while the average stride width, the percentage of double stance phase, unaffected and affected side stance phase, and the ratio between unaffected and affected side stance phase had all decreased significantly. After the intervention, the average step speed, frequency and length of the AFO and walking support band groups had increased significantly compared with the conventional rehabilitation group, while the average stride width of the AFO group, and the stride width, the percentage of double stance phase and unaffected side stance phase of the walking support band group had decreased significantly. After the treatment, the average percentages of double stance phase and unaffected side stance phase of the walking support band group had decreased significantly more than in the AFO group.Conclusions:A walking support band can significantly improve the abnormal gait of stroke survivors and is superior to an ankle-foot orthosis when combined with conventional rehabilitation therapy.

Objective To evaluate the effects of oxycodone combined with incision infiltration with ropivacaine on postoperative outcomes in the patients undergoing laparoscopic cholecystectomy.Methods Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 33-64 yr,weighing 45-88 kg,scheduled for elective laparoscopic cholecystectomy under general anesthesia,were divided into 2 groups (n=40 each) using a random number table:patient-controlled intravenous analgesia group (group P) and oxycodone combined with incision infiltration group (group O).In group P,fentanyl 1-2 μg/kg was intravenously infused after cholecystectomy,and patient-controlled intravenous analgesia was performed with sufentanil at the end of surgery.In group O,oxycodone 0.05-0.10 mg/kg was intravenously injected after cholecystectomy,incision infiltration was performed with 0.5％ ropivacaine before suturing,and visual analog scale score was maintained ≤ 3.The emergence time,time to first flatus,time to liquid diet,first ambulation time,length of hospital stay after operation and adverse reactions were recorded.Results Compared with group P,the time to first flatus,time to liquid diet,first ambulation time and length of hospital stay after operation were significantly shortened,the incidence of urinary retention and nausea and vomiting was decreased (P＜0.05),and no significant change was found in the emergence time in group O (P＞0.05).Conclusion Combination of oxycodone and incision infiltration with ropivacaine can promote postoperative outcomes in the patients undergoing laparoscopic cholecystectomy.