As an adjuvant therapy,transarterial chemoembolization(TACE)can prolong the disease-free survival and overall survival of patients with primary liver cancer(PCL).However,postoperative adverse reactions and recurrence still possibly persist.Based on years of clinical practice,Professor Lin Lizhu proposes that patients with PCL undergoing TACE exhibit pathological mechanisms characterized by deficiency,stagnation,toxicity,and stasis.In clinical practice,these patients can be treated with Chinese herbal medicine based on the therapeutic principle of strengthening spleen and soothing liver.The treatment strategy involves:invigorating spleen and stomach to restore healthy qi,soothing liver and nourishing blood to support liver function,and detoxifying and dispersing stasis to prevent recurrence.Derived from the classic formula Sini San,Professor Lin has developed Sini Kang'ai Formula,which mainly consists of Eupolyphaga Steleophaga,Bupleuri Radix,Paeoniae Radix Alba,Aurantii Fructus Immaturus,Glycyrrhizae Radix et Rhizoma,Codonopsis Radix,Persicae Semen,Cremastrae Pseudobulbus Pleiones Pseudobulbus,etc.In clinical application,Sini Kang'ai Formula should be flexibly modified depending on the characteristic symptom patterns of patients during the perioperative period of TACE,thus to alleviate postoperative adverse reactions,prevent tumor recurrence,prolong disease-free survival and overall survival,and improve patients' quality of life.

Neuronal injury in glaucoma persists despite effective intraocular pressure (IOP) control, necessitating neuroprotective strategies for retinal ganglion cells (RGCs). In this study, we investigated the neuroprotective role of the γ-hydroxybutyrate analog HOCPCA in a glaucoma model, focusing on its effects on CaMKII signaling, oxidative stress, and neuroinflammatory responses. Retinal tissue from high IOP animal models was analyzed via proteomics. In vitro mouse retinal explants were subjected to elevated pressure and oxidative stress, followed by HOCPCA treatment. HOCPCA significantly mitigated the RGC loss induced by oxidative stress and elevated pressure, preserving neuronal function. It restored CaMKIIα and β levels, preserving RGC integrity, while also modulating oxidative stress and neuroinflammatory responses. These findings suggest that HOCPCA, through its interaction with CaMKII, holds promise as a neuroprotective therapy for glaucoma.
Animals ; Retinal Ganglion Cells/metabolism* ; Glaucoma/pathology* ; Oxidative Stress/drug effects* ; Neuroprotective Agents/pharmacology* ; Mice ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotection/drug effects* ; Male ; Intraocular Pressure/drug effects*

OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

BACKGROUND:Although aromatase inhibitors significantly improve the clinical benefit of patients with hormone receptor-positive breast cancer,its associated adverse event-osteoporosis seriously affects the quality of life of patients.Huangqi Bushen Huoxue Decoction can effectively prevent the occurrence of aromatase inhibitor-induced osteoporosis,but its mechanism of action is unclear.OBJECTIVE:To investigate the effects of Huangqi Bushen Huoxue Decoction on osteoclast activity in a mouse model of osteoporosis induced by aromatase inhibitors and relevant mechanisms.METHODS:Sixty 8-week-old female C57BL/6J mice were randomly divided into sham operation group,model group,high-,medium-and low-dose Huangqi Bushen Huoxue Decoction,and positive control group,with 10 mice in each group.Bilateral ovaries were removed to establish postmenopausal animal models in all the groups except for the sham operation group.After 1 week of recovery,letrozole was injected subcutaneously to establish postmenopausal osteoporosis models via subcutaneous injection of letrozole(an aromatase inhibitor).The high-,medium-and low-dose Huangqi Bushen Huoxue Decoction groups were intragastrically given 19.24,9.62 and 4.81 g/kg/d Huangqi Bushen Huoxue Decoction(once a day),respectively.The positive control group was given alendronate 5mg/kg once a week.After 3 months of administration,Micro-CT was used to detect tibial bone mineral density and bone microstructure.Hematoxylin-eosin staining and tartrate-resistant acid phosphatase staining of the femur were performed.Immunohistochemistry was used to detect the protein expression of receptor activator of nuclear factor-κB ligand and osteoprotectin in the femur.ELISA was used to detect the serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,the model group showed a significant decrease in bone mineral density,sparse and fractured trabecular morphology,and a significant increase in serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,indicating that the model of aromatase inhibitor-induced osteoporosis was successfully constructed.(2)Compared with the model group,the high-,medium-,and low-dose Huangqi Bushen Huoxue Decoction groups showed significant improvement in bone mineral density and bone microstructure,thickening and densification of trabecular morphology,significantly decreased serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,a decrease in the number of osteoclasts and the expression of receptor activator of nuclear factor-κB ligand proteins,and an increase in the expression of osteoprotegerin.To conclude,Huangqi Bushen Huoxue Decoction may regulate the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin signaling pathway,inhibit osteoclast activity,improve trabecular morphology and bone microstructure,and increase bone mineral density,thus preventing the occurrence and development of aromatase inhibitor-induced osteoporosis.

BACKGROUND:Although aromatase inhibitors significantly improve the clinical benefit of patients with hormone receptor-positive breast cancer,its associated adverse event-osteoporosis seriously affects the quality of life of patients.Huangqi Bushen Huoxue Decoction can effectively prevent the occurrence of aromatase inhibitor-induced osteoporosis,but its mechanism of action is unclear.OBJECTIVE:To investigate the effects of Huangqi Bushen Huoxue Decoction on osteoclast activity in a mouse model of osteoporosis induced by aromatase inhibitors and relevant mechanisms.METHODS:Sixty 8-week-old female C57BL/6J mice were randomly divided into sham operation group,model group,high-,medium-and low-dose Huangqi Bushen Huoxue Decoction,and positive control group,with 10 mice in each group.Bilateral ovaries were removed to establish postmenopausal animal models in all the groups except for the sham operation group.After 1 week of recovery,letrozole was injected subcutaneously to establish postmenopausal osteoporosis models via subcutaneous injection of letrozole(an aromatase inhibitor).The high-,medium-and low-dose Huangqi Bushen Huoxue Decoction groups were intragastrically given 19.24,9.62 and 4.81 g/kg/d Huangqi Bushen Huoxue Decoction(once a day),respectively.The positive control group was given alendronate 5mg/kg once a week.After 3 months of administration,Micro-CT was used to detect tibial bone mineral density and bone microstructure.Hematoxylin-eosin staining and tartrate-resistant acid phosphatase staining of the femur were performed.Immunohistochemistry was used to detect the protein expression of receptor activator of nuclear factor-κB ligand and osteoprotectin in the femur.ELISA was used to detect the serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,the model group showed a significant decrease in bone mineral density,sparse and fractured trabecular morphology,and a significant increase in serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,indicating that the model of aromatase inhibitor-induced osteoporosis was successfully constructed.(2)Compared with the model group,the high-,medium-,and low-dose Huangqi Bushen Huoxue Decoction groups showed significant improvement in bone mineral density and bone microstructure,thickening and densification of trabecular morphology,significantly decreased serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,a decrease in the number of osteoclasts and the expression of receptor activator of nuclear factor-κB ligand proteins,and an increase in the expression of osteoprotegerin.To conclude,Huangqi Bushen Huoxue Decoction may regulate the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin signaling pathway,inhibit osteoclast activity,improve trabecular morphology and bone microstructure,and increase bone mineral density,thus preventing the occurrence and development of aromatase inhibitor-induced osteoporosis.

Objective:To investigate the effect of astragaloside A (AS-A) on the photoreceptor degeneration induced by sodium iodate (NaIO 3) and its related mechanism. Methods:Sixty healthy male C57BL/6J mice, aged 6-8 weeks, were randomly divided into normal control (NC) group, NaIO 3 group, and ASA group, with twenty mice in each group. 30 min before modeling, AS-A group mice were intraperitoneally injected with 100 μl AS-A at a dose of 100 mg/kg body weight. 30 min later, mice in NaIO 3 group and AS-A group were intraperitoneally injected with 100 μl NaIO 3 at a dose of 30 mg/kg body weight. Subsequently, AS-A group mice were administered AS-A twice daily at 12 h intervals until the end of the experiment. On day 1 post-modeling, zonula occludens-1 (ZO-1) immunohistochemistry was performed to observe the structure of retinal pigment epithelium (RPE) cells; real-time quantitative polymerase chain reaction (qPCR) was conducted to detect the mRNA expression of various retinal chemokine ligand-2 ( Ccl2), interleukin-1 beta ( Il-1β), mixed lineage kinase domain-like protein ( Mlkl), receptor-interacting protein kinase 3 ( Ripk3), and tumor necrosis factor ( Tnf). On day 3 post-modeling, immunohistochemistry was performed to observe the expression of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acid protein (GFAP) in the retina; TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to detect photoreceptor cell death in each group. On day 4 post-modeling, fundus morphology of mice in each group was observed by fundus color photography and optical coherence tomography (OCT). Hematoxylin-eosin staining (HE) was used to observe the morphological structure of the retina in each group. Inter-group comparisons between two groups were conducted using independent samples t-test, while comparisons among three groups were performed using one-way ANOVA. Results:Fundus color photography and OCT examination showed that a large number of scattered yellow-white subretinal nodular structures in the fundus of NaIO 3 group mice, and a large number of strong reflection areas in the RPE layer. The number of strong reflection areas in the RPE layer was reduced in the AS-A group. Immunohistochemical analysis of ZO-1 showed that ZO-1 was largely lost on the RPE cell membrane in that NaIO 3 group; whereas in the AS-A group, ZO-1 was evenly distributed on the RPE cell membrane. HE staining results showed circular black deposits were visible in the RPE layer of the NaIO 3 group, and the inner and outer segments of photoreceptors were severely damaged, with a significant decrease in the number of outer nuclear layer (ONL) cell nuclei; whereas in the AS-A group, the RPE layer pigments were orderly, the inner and outer segments of photoreceptors were intact, and the number of ONL cell nuclei significantly increased. The results of TUNEL staining show that numerous TUNEL-positive cell nuclei were observed in the ONL of the retina in the NaIO 3 group, while the number of TUNEL-positive cell nuclei in the ONL of the retina was significantly reduced in the AS-A group, with statistically significant differences ( t=2.66, P<0.05). The analysis of qPCR data showed that compared with the AS-A group, the relative expression levels of Mlkl, Ripk3, Ccl2, Il-1β and Tnf mRNA in the retina were significantly increased in the NaIO 3 group, with statistically significant differences ( F=39.18, 10.66, 53.51, 41.40, 24.13; P<0.001). Immunohistochemical staining results showed that compared with NC group and AS-A group, the positive expression of GFAP in retina of NaIO 3 group was significantly increased, and the difference was statistically significant ( F=9.62, P<0.05). Conclusion:AS-A antagonizes NaIO 3-induced photoreceptor degeneration in part by inhibiting photoreceptor cell death and neuroinflammation. Meanwhile, AS-A treatment protects against NaIO 3-triggered perturbation of retinal homeostasis.

Objective : To explore the relationship between geriatric nutritional risk index( GNRI) and perioperative nutritional status，postoperative recovery and complications in elderly patients with gastric cancer． Methods : In this retrospective study，212 elderly patients ( aged ≥60 years ) with gastric cancer who underwent gastrectomy were recruited．GNRI was used to retrospectively assess the patients' preoperative nutritional status ，and analyze the relationship between GNRI and perioperative nutritional status，postoperative recovery and complications．The ROC curve was applied to explore the value of GNRI in predicting postoperative complications. Results : The inci- dence of preoperative nutritional risk in elderly patients undergoing gastric cancer surgery was 45. 07%．Compared with the patients whose GNRI＞98 points，the patients whose GNRI≤98 points had different degrees of decrease in serum total protein，albumin，prealbumin，hemoglobin and lymphocyte counts before surgery，day 1 and day 5－8 after surgery (P ＜0. 05) ．The patients whose GNRI ＜92 points had longer postoperative hospital stay than those with GNRI＞98 points (P＜0. 05) ．With the decrease of GNRI scores，the incidence of complications showed an upward trend(P＜0. 001) ．The multivariate analysis of the relationship between GNRI and postoperative complica- tions showed that TNM staging of III －IV and GNRI ＜92 points were independent risk factors for complications. GNRI had a good predictive value for the occurrence of complications (AUC = 0. 639，95% CI : 0. 570－0. 703，P = 0. 001，Cut-off value : 92. 21) ． Conclusion GNRI can be used for preoperative nutritional assessment for eld- erly gastric cancer patients．Patients with GNRI＜92. 21 points should be actively given nutritional therapy to im- prove perioperative nutritional status，speed up postoperative recovery，and reduce the occurrence of complications.

Objective: To observe ascitic interleukin-7 expression level in cirrhotic patients complicated with spontaneous bacterial peritonitis, and to detect the effect of recombinant human IL-7 on CD4⁺ and CD8⁺T lymphocyte function. Methods: A total of 84 patients with liver cirrhosis who were hospitalized from August 2017 to April 2018 were selected. Among them, 51 cases were complicated with cirrhosis and untainted ascites, and 33 cases were cirrhosis complicated with spontaneous bacterial peritonitis. Peripheral blood and ascites were collected routinely. The levels of IL-7 in peripheral blood and ascites were measured by enzyme-linked immunosorbent assay. CD4⁺T cells and CD8⁺T cells were purified from ascites, and were stimulated with recombinant IL-7. Cellular proliferation, key transcription factors for mRNA, and cytokines production by CD4⁺T cells in response to IL-7 stimulation was measured. mRNA expression corresponding to perforin, granzyme B, and granulysin as well as cytokines production by CD8⁺T cells was also measured in response to IL-7 stimulation. Cytolytic and non-cytolytic activity of CD8⁺T cells in response to IL-7 stimulation was also investigated in both direct and indirect contact co-culture system. Measurement data of the normal distribution were compared between the two groups by Student’s t-test and the data before and after stimulation were compared by paired t-test. Measurements that did not conform to normal distribution were compared between the two groups using Mann-Whitney U test, and data before and after stimulation were compared using Wilcoxon paired test. Results: There was no significant statistical difference in serum IL-7 levels between the two groups [(5 001 ± 1 458) pg/ml vs. (4 768 ± 1 128) pg/ml, P = 0.41]. The level of ascitic IL-7 in cirrhotic patients complicated with SBP was significantly lower than cirrhosis patients with untainted ascites [(966.4 + 155.8) pg/ml vs. (792.1 + 126.4) pg/ml, P < 0.01]. Recombinant IL-7 stimulation promoted the proliferation of CD4⁺ and CD8⁺T cells from ascites in patients with liver cirrhosis complicated by SBP. T-bet mRNA relative expression and IFN-γ secretion in CD4⁺T cells was also elevated in response to IL-7 stimulation in vitro. Moreover, IL-7 stimulation also increased the mRNA expressions of perforin, granzyme B, and granulysin as well as productions of IFN-γ and TNF-α by CD8⁺T cells. Recombinant IL-7 stimulation elevated cytolytic and non-cytolytic activity of CD8⁺T cells from ascites in patients with liver cirrohosis complicated by SBP, which manifested as increased target cell death and IFN-γ production in both direct and indirect contact co-culture system. Conclusion Ascitic IL-7 promotes T lymphocyte function in patients with liver cirrhosis complicated with SBP.

Signal transducer and activator of transcription 3 (STAT3) and Chemokine CX3C ligand 1 (Fractalkine/CX3CL1) play important roles in vascular inflammation and injury. To study if STAT3 promotes vascular endothelial cell proliferation and migration through fractalkine, we overexpressed or knocked down STAT3 in vascular endothelial cells, and used quantitative real-time PCR and Western blotting to determine the effect of STAT3 on fractalkine expression. The wild type and STAT3 binding site mutant fractalkine promoter luciferase reporter plasmids were constructed, and luciferase activity assays were used to explore the effect of STAT3 on the transcriptional activity of the fractalkine promoter. MTT assays were used to detect the effect of overexpression or knockdown of STAT3 or fractalkine on the proliferation rate of vascular endothelial cells. Scratch assays were used to detect the effect of overexpression or knockdown of STAT3 or fractalkine on vascular endothelial cell migration. There results showed that overexpression of STAT3 could promote fractalkine expression, and knockdown of STAT3 could down-regulate fractalkine expression. STAT3 could directly bind to the promoter of fractalkine to promote its transcriptional activity via binding the GAS site of the fractalkine promoter. Knockdown of STAT3 could inhibit the migration of vascular endothelial cell, and overexpression of fractalkine antagonized this inhibition. Our data concluded that STAT3 promotes the proliferation and migration of vascular endothelial cell by binding the GAS site of the fractalkine promoter to promote fractalkine transcriptional activity and expression.
Cell Proliferation ; Chemokine CX3CL1 ; Endothelial Cells ; Promoter Regions, Genetic ; STAT3 Transcription Factor

Objective To investigate the residents' acceptance and the influencing factors of the hierarchical medical system in Xuzhou, and to suggest on effective system implementation. Methods Xuzhou residents free of cognitive impairment and over 18 years old were sampled for questionnaire survey in July-August 2016, to study their acceptance of their basics and acceptance of the system. 1 550 questionnaires were distributed, and 1 473 valid ones were recovered. The count data were expressed as constituent ratio, and χ2test was used for single-factor analysis, with binary logistic regression analysis for multi-factor analysis. Results 71. 0% of the residents embraced this system. Their acceptance varies significantly with their age, place of residence, education, annual average monthly income, self-rated health status, physical examination experience, conditions of chronic diseases, medical visit experience at primary healthcare institutions, and their awareness of the system (P<0.05). Conclusions The acceptance of the system by Xuzhou residents needs to be elevated, by means of greater promotional efforts, capacity building for primary institutions, so as to fully leverage the system to serve the residents.