Aging is an inevitable, physiological process of the human body, leading to deterioration in bodily function and increased susceptibility to various diseases. Effective endogenous therapeutic strategies for anti-aging and related diseases remain limited. Exercise confers multifaceted benefits to physical health by augmenting osteogenic and myogenic processes, enhancing cardiovascular and nervous system function, and attenuating chronic inflammation. Angiogenesis and lymphangiogenesis play pivotal roles in anti-aging, tissue repair, and immune response modulation, underscoring their potential as therapeutic targets for age-related diseases. Modulating angiogenic and lymphangiogenic pathways may provide a promising strategy for mitigating vascular decline and immune system dysfunction associated with aging. Exercise-induced endogenous angiogenesis and lymphangiogenesis can exert beneficial effects on physiological function, thereby representing a potential therapeutic paradigm for combating age-related decline and diseases. This review offers a thorough summary of the present knowledge regarding angiogenesis and lymphangiogenesis induced by exercise, encompassing the underlying mechanisms and the effects in different organs. In addition, it explores the potential of physical activity as a non-pharmacological intervention for anti-aging strategies and disease management, offering novel insights into the intersection of physical activity, aging, and disease progression.
Humans ; Lymphangiogenesis/physiology* ; Aging/physiology* ; Exercise/physiology* ; Animals ; Neovascularization, Physiologic/physiology* ; Angiogenesis

Objective To screen the anti-Helicobacter pylori gastritis active components of the ethyl acetate extract of Alpinia officinarum Hance.Methods The"knock-out"strategy combined with high-performance liquid chromatography(HPLC)detection was developed to separate the components of the ethyl acetate extract of A.officinarum while obtaining the negative samples without the components.A human gastric epithelial cell(GES-1)model of H.pylori gastritis was established,and the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-8(IL-8)and interleukin-1β(IL-1β)in the supernatant of the cells were determined by enzyme-linked immunosorbent assay(ELISA).Results The total flavonoid fraction,the negative fraction without total diphenylheptanoids,the negative fraction without 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone(DHPA),and galangin significantly reduced IL-6 levels in the supernatant of H.pylori infected GES-1 cells at a concentration of 8 μg·mL-1 with 24 h incubation.The total flavonoid fraction strongly inhibited the release of IL-6,TNF-α,IL-8,and IL-1β from H.pylori gastritis GES-1 cells at a concentration of 16 μg·mL-1.Conclusions The total flavonoid fraction is the major anti-H.pylori gastritis active component of the ethyl acetate extract of A.officinarum.The results lay the foundation for further elucidation of the material basis of A.officnarum against H.pylori gastritis.

Objective:To establish a risk prediction model of liver failure after liver resection for hepatocellular carcinoma.Method:A retrospective case-control study was designed. Clinical data and laboratory results, including gender, age, and preoperative 18 laboratory indicators, were collected from 320 patients with hepatocellular carcinoma undergoing liver resection in Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University from January 1, 2013 to December 31, 2023. According to the surgical time, 252 cases in the training cohort were divided into 62 and 190 cases with and without postoperative liver failure, respectively. Of the 68 cases in validation cohort, 34 developed postoperative liver failure and 34 did not. Binary Logistic regression analysis was used to conduct univariate analysis of gender, age, and 18 preoperative laboratory indicators, and multivariate analysis was carried out for significant results to determine the influencing factors of liver failure after liver resection for hepatocellular carcinoma, and Logistic regression model was established.Result:In the training cohort, indicators significantly associated with liver failure after liver resection for hepatocellular carcinoma included age ( P=0.016), platelets ( P=0.005), prealbumin ( P<0.001), and alkaline phosphatase ( P<0.001). Logistic regression was used to construct a nomogram model and draw a calibration curve by combining these four indicators. In the training cohort, the nomogram model showed good discriminability in predicting the risk of liver failure after hepatectomy for hepatocellular carcinoma. The area under the curve of was 0.82 (95% CI 0.76-0.88), and the sensitivity was 73% and specificity was 80% when the optimal cut-off value was 0.2646. In the validation cohort, the predictive performance of the nomogram model was comparable to that of the training cohort, with an area under the curve of 0.81 (95% CI 0.71-0.92), sensitivity of 82%, and specificity of 77%. Conclusion:Preoperative platelet and prealbumin decreases, alkaline phosphatase increases, and elderly patients are prone to liver failure after liver resection. The nomogram model constructed with preoperative test data has shows good discriminatory ability and accuracy in predicting liver failure after liver resection for hepatocellular carcinoma.

Objective: To study the buccolingual inclination of posterior premolars and molars and the curve of Wilson in patients with different sagittal skeletal patterns, to explore the compensation mechanism of horizontal inclination of posterior teeth in patients with different sagittal skeletal patterns and to provide a reference for the control of posterior tooth inclination in the treatment of bone malocclusion. Methods: This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Ninety CBCT scans of adults and ninety scans of adolescents before orthodontic treatment were evaluated in this cross-sectional study. There were 30 skeletal Class I, Class Ⅱ, and Class Ⅲ patients in the adult group and adolescent group. The inclination angles of posterior teeth and the curve of Wilson of first and second molars were measured, and data were analyzed between adolescents and adults with different sagittal skeletal patterns. Results : Compared with skeletal Class Ⅰ adult patients, the upper posterior molar inclination of skeletal Class Ⅱ patients was significantly lower, and the lower posterior molar inclination was significantly higher. Compared with skeletal ClassⅠ adult patients, the upper posterior molar inclination of skeletal Class Ⅲ adult patients was higher, and the lower posterior molar inclination was significantly lower. The Wilson curve of the second molar in skeletal Class Ⅱ adult patients was significantly higher than that in the other groups. Compared with skeletal ClassⅠ adolescent patients, skeletal Class Ⅲ adolescent patients had a significantly higher upper posterior molar inclination; however, no difference was found between the inclination of the posterior teeth between skeletal Class Ⅰ, Class Ⅱ and Class Ⅲ adolescent patients. Comparing adolescent and adult samples, in skeletal Class Ⅱ patients, adults showed more lingual inclination than adolescents in the upper posterior teeth and less lingual inclination in the lower posterior teeth except for the mandibular first molar. Comparing adolescent and adult samples, in skeletal Class Ⅲ patients, adults showed more lingual inclination than adolescents in the lower posterior teeth except for the mandibular second molars and showed no difference in the upper posterior teeth. Conclusions The inclination of the posterior teeth and the curve of Wilson show significant differences between the three sagittal skeletal patterns. Compared with those of skeletal Class Ⅰ patients, the posterior teeth of skeletal Class Ⅱ patients show more lingual inclination in the upper arch and less lingual inclination in the lower arch. Meanwhile, posterior teeth of skeletal Class Ⅲ patients show more lingual inclination in the lower arch and maintain the inclination in the upper arch.

OBJECTIVE To establish the quality evaluation method of Polyporus formula granules, and to comprehensive evaluate the quality uniformity and stability of products from different manufacturers. METHODS The fingerprint of Polyporus formula granules was determined by HPLC. Shim-pack GIST C18-AQ(4.6 mm×150 mm, 3 μm) was used, mobile phase was acetonitrile-water with gradient elution, volume flow rate was 1.0 mL·min-1, detection wavelength was 350 nm (0-3 min) and 250 nm(3-35 min), column temperature was 30℃. HPLC fingerprints of Polyporus formula granules from different manufacturers were established, common peaks were identified, similarities were evaluated and cluster analysis were performed. HPLC was used to determine the contents of 4 active ingredients, and the quality of 16 batches of samples was analyzed and evaluated. RESULTS The established HPLC fingerprint of Polyporus formula granules defined 14 common peaks and identified 6 common components. They were peak 2(uridine), peak 4(guanosine), peak 6(adenosine), peak 12(polyporusteron B), peak 13(polyporusteron A), peak 14(polyporusteron C). The similarity of 16 batches of samples were 0.609-0.982, and could be clustered into 2 categories by cluster analysis. Guanosine, adenosine, polyporusteron B and polyporusteron A all showed good linear relationships(r ≥ 0.999 7), RSDs of instrument precision, stability and reproducibility tests were <3%. The average recoveries were 98.22%, 99.32%, 99.56%, 99.15%, RSD<3%(n=6). The contents of guanosine, adenosine, polyporusteron B, polyporusteron A in 16 batches of samples were 6.326-28.006, 13.392-44.058, 10.324-30.335, 9.270-26.964 μg·g-1.CONCLUSION There is considerable quality difference among different manufacturers. The established fingerprint combine with the compound determination can comprehensively and accurately evaluate the internal quality of Polyporus formula granules, and provide a basis for the overall improvement of the quality.

Purpose: This study was performed to investigate the association of Glasgow prognostic score (GPS), combined positive score (CPS), and clinicopathological characteristics of locally advanced rectal cancer. Methods: Between February 2012 and February 2018, 103 patients with locally advanced rectal cancer treated by neoadjuvant chemoradiotherapy and total mesorectal excision (TME) were retrospectively evaluated. Results: According to the classification of the GPS, 85 (82.5%), 13 (12.6%), and 5 patients (4.9%) were classified as a score of 0, 1, and 2, respectively. Patients were classified into the GPS-low group (GPS of 0, n = 85) and GPS-high group (GPS of 1 or 2, n = 18) with an area under the curve of 0.582 for overall survival (OS). The mean programmed death-ligand 1 (PD-L1) CPS of the whole group was 2.24 (range, 0–70). The PD-L1 CPS of the GPS-high group was higher than the GPS-low group (P < 0.001). Multivariate analysis by Cox proportional hazards model indicated that GPS was associated with OS and diseasefree survival (DFS). Furthermore, PD-L1 CPS was associated with DFS (hazard ratio, 1.050; 95% confidence interval, 1.017– 1.083; P = 0.003). Conclusion Elevated GPS was related to the PD-L1 CPS. GPS and PD-L1 CPS were associated with the prognosis of locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by TME.

Objective:To investigate the changes of paraspinal muscles in patients with degenerative lumbar scoliosis (DLS) and its correlation with lumbar kyphosis.Methods:The clinical data of 67 female patients with degenerative lumbar scoliosis, with an average of 65.4±5.6 years old (rang 52-83 years old), were retrospectively analyzed. There were 35 patients of DLS with lumbar degenerative kyphosis (LDK) in the DLS+LDK group, with an average of 64.60±5.40 years old (rang 52-75 years old), and 32 patients of lumbar scoliosis without lumbar kyphosis in the DLS group, with an average of 66.22±5.8 years old (rang 55-83 years old). The cross-sectional area (CSA) and the percentage of fat infiltration area (FIA%) of erector spinae and multifidus muscles of the 5 intervertebral disc levels (from L 1-2 to L 5S 1) were measured by MRI using Image J software (ver. 1.51 k, National Institutes of Health, USA). The curve direction, Cobb angle, sagittal vertical axis (SVA), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS) were evaluated and recordedin both groups using an anteroposterior radiograph in the standing position, and the correlation between the changes of paraspinal muscles and these factors was analyzed. Results:The TLK, LL, and SVA values of the DLS+LDK group (11.85°±7.89°, -9.35°±8.70° and 70.16±76.94 mm) were higher than those of the DLS group (7.47°±5.06°, -26.46°±10.26° and 39.45±38.18mm) ( t=2.73, P=0.008; t=7.38, P<0.001; t=2.10, P=0.041). The TK, PI, and SS values of the DLS+LDK group (16.36°±13.52°, 42.49°±11.70° and 11.89°±10.03°) were lower than those of the DLS group (23.60°±10.23°, 49.38°±11.92° and 21.21°±8.28°) ( t=2.45, P=0.017; t=2.38, P=0.020; t=4.13, P<0.001). The differences of Cobb and PT were not statistically significant between the two groups. The cross-sectional areas of L 1-2, L 2-3, L 3-4 intervertebral disc levels of erector spinae of the DLS+LDK group (1 328.36±339.16 mm 2, 1 331.98±305.76 mm 2 and 12 53.58±275.86 mm 2) were lower than those of the DLS group (1 564.16±312.68 mm 2, 1 574.80±325.92 mm 2 and 1 427.18±278.82 mm 2) ( t=0.40, P=0.004; t=0.81, P=0.002; t=0.306, P=0.013). The cross-sectional areas of L 1-2, L 2-3, L 3-4, L 4-5 intervertebral disc levels of multifidus muscles of the DLS+LDK group (225.07±59.80 mm 2, 228.38±87.44 mm 2, 436.40±117.99 mm 2 and 666.55±184.13 mm 2) were lower than those of the DLS group (264.28±44.27 mm 2, 384.85±75.52 mm 2, 576.10±109.92 mm 2 and 801.52±145.83 mm 2) ( t=0.21, P=0.004; t=0.42, P<0.001; t=0.52, P<0.001; t=0.37, P=0.002). The differences of FIA% of erector spinae and multifidus muscles at all lumbar spine levels were not statistically significant between the two groups. The cross-sectional areas of L 1-2, L 2-3, L 3-4 intervertebral disc levels of erector spinae and L 1-2, L 2-3, L 3-4, L 4-5 intervertebral disc levels of multifidus muscles of the two groups were negatively correlated with LL values ( r=-0.37, P=0.002; r=-0.34, P=0.005; r=-0.21, P=0.049; r=-0.34, P=0.005; r=-0.61, P<0.001; r=-0.65, P<0.001; r=-0.55, P<0.001), and positively correlated with SS ( r=0.42, P<0.001; r=0.37, P=0.002; r=0.27, P=0.027; r=0.38, P=0.001; r=0.53, P<0.001; r=0.46, P<0.001; r=0.42, P<0.001). The cross-sectional areas of L 3-4 intervertebral disc levels of erector spinae and L 1-2, L 2-3 intervertebral disc levels of multifidus muscles of the two groups were positively correlated with PI ( r=0.25, P=0.039; r=0.33, P=0.006; r=0.35, P=0.004). There was no correlation between the FIA% of erector spinae and multifidus muscles at all lumbar spine levels and the sagittal and pelvic parameters in both groups. Conclusion:Paravertebral muscle atrophy is more obvious in patients with degenerative lumbar scoliosis with lumbar kyphosis, which may be related to the reduce of lumbar lordosis and sacral slope. Patients with lumbar scoliosis with a smaller PI are more likely to experience paravertebral atrophy and increased loss of lumbar lordosis, and ultimately leading to lumbar kyphosis.

Objective:To investigate the potential molecular mechanisms of liver cancer cell-derived secretory autophagosomes, extracellular vesicles expressing LC3B (LC3B + EVs), in promoting the exhaustion of CD8 + T cells. Methods:The proportions of LC3B + EVs and PD-1 + CD8 + T cells in peripheral blood and ascites of liver cancer patients were measured by flow cytometry. Spearman correlation test was used to analyze the correlation between the proportions of LC3B + EVs and PD-1 + CD8 + T cells. Peripheral blood mononuclear cells (PBMCs) from healthy donors were treated with LC3B + EVs or heat shock protein 90α (HSP90α) blocking antibody-pretreated LC3B + EVs for 72 h in the presence of αCD3/CD28 antibodies and IL-2 in vitro. The proportions of PD-1 + CD8 + T and IFN-γ + CD8 + T cells and the concentrations of IL-2, TNF-α and IFN-γ in the supernatants were all detected by flow cytometry. Results:The proportions of LC3B + EVs and HSP90α + LC3B + EVs in plasma and ascites from liver cancer patients were significantly higher than those in healthy control group and non-cancerous ascites group. The level of plasma LC3B + EVs, especially HSP90α + LC3B + EVs, was significantly correlated with the percentage of exhausted PD-1 + CD8 + T cells. In addition, LC3B + EVs from human liver cancer cells up-regulated the percentage of exhausted CD8 + T cells in vitro. However, LC3B + EVs pretreated with HSP90α blocking antibody could significantly inhibit LC3B + EVs-induced CD8 + T cell exhaustion. Conclusions:Liver cancer cell-derived LC3B + EVs could effectively induce CD8 + T cell exhaustion mainly through the membrane-bound HSP90α.

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). But little is known about how alanine-serine-cysteine transporter type-2 (ASCT2), a high affinity glutamine transporter, affects HSC senescence and SASP during liver fibrosis. Here, we identified ASCT2 is mainly elevated in aHSCs and positively correlated with liver fibrosis in human and mouse fibrotic livers. We first discovered ASCT2 inhibition induced HSCs to senescence in vitro and in vivo. The proinflammatory SASP were restricted by ASCT2 inhibition at senescence initiation to prevent paracrine migration. Mechanically, ASCT2 was a direct target of glutaminolysis-dependent proinflammatory SASP, interfering IL-1α/NF-κB feedback loop via interacting with precursor IL-1α at Lys82. From a translational perspective, atractylenolide III is identified as ASCT2 inhibitor through directly bound to Asn230 of ASCT2. The presence of -OH group in atractylenolide III is suggested to be favorable for the inhibition of ASCT2. Importantly, atractylenolide III could be utilized to treat liver fibrosis mice. Taken together, ASCT2 controlled HSC senescence while modifying the proinflammatory SASP. Targeting ASCT2 by atractylenolide III could be a therapeutic candidate for liver fibrosis.

【Objective】 To analyze the quality level of the laboratory pre-analytical phase, so as to take effective quality improvement interventions to further standardize the operation and provide basis for ensuring the quality of blood testing. 【Methods】 Pre-analytical phase quality indicators of blood screening laboratory in Shanghai Blood Center were established, and those had serious impact on blood safety were defined as the sentinel indicators. The pre-analytical quality level of our laboratory from 2018 to 2020 was statistically analyzed in terms of four parts including sample collection, preservation and submission, centrifugation and quality inspection, which contained 17 indicators. 【Results】 Eleven sentinel indicators were established, and the order of peak value from high to low in three years was as follows: " label omission" rated at 0.000 62% (2020), " label error" 0.000 57% (2018), " inappropriate storage of samples before detection" 0.007 39 (2018), " unqualified application form for sample detection" 0.007 39 (2018). The causes were analyzed and relevant measures were taken. Six monitoring indicators were established, and the order of peak value from high to low in three years was as follows: " insufficient sample" rated at 0.002 59% (year 2018), " hemolysis" 0.002 80% (year 2020), " pale color of blood supernatant (diluted)" 0.000 86 (2018), " automatic sampling interfered by blood clot" 0.027 02% (2018). 【Conclusion】 The quality indexes of pre-analytical phase in our laboratory have reached the level of domestic and international clinical laboratories. The establishment of pre-analytical quality indicators and sentinel indicators, with effective analysis and application, can fully record and monitor the quality of each link before laboratory testing, which is helpful to timely identify risks, detect deviations, and quickly implement corrective and preventive measures, thus further ensure the safety of clinical blood use.