ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA （lncRNA MANCR） on the proliferation，migration， and epithelial mesenchymal transition （EMT） of gastric cancer （GC） cells by regulating the microRNA-50-5p （miR-150-5p）/non-metastatic melanoprotein B （GPNMB） axis. MethodsThe mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro， and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group （routine culture），sh-NC group （with sh-NC transfected），sh-MANCR group （with sh-MANCR transfected），sh-MANCR + anti-NC group （with sh-MANCR and anti-NC both transfected），and sh-MANCR + anti-miR-150-5p group （with sh-MANCR and anti-miR-150-5p both transfected）. The mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin，N-cadherin，Vimentin， and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue，and the expression of miR-150-5p was lower than that in adjacent tissue （P<0.05）. Compared with that in GES-1，lncRNA MANCR expression in BGC-823 cells was increased （P<0.05）. Compared with those in the sh-NC group and control group，the EdU-positive cell rate，migration number，invasion number，the mRNA expressions of lncRNA MANCR and GPNMB， and the expressions of protein，N-cadherin protein， and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ，and the protein expressions of miR-150-5p and E-cadherin were higher （P<0.05）. Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group，the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate，migration number，invasion number，mRNA expressions of GPNMB， and expressions of protein，N-cadherin protein， and Vimentin protein were increased （P<0.05）. lncRNA MANCR could target the negative regulation of miR-150-5p，and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation，migration， and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.

ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA （lncRNA MANCR） on the proliferation，migration， and epithelial mesenchymal transition （EMT） of gastric cancer （GC） cells by regulating the microRNA-50-5p （miR-150-5p）/non-metastatic melanoprotein B （GPNMB） axis. MethodsThe mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro， and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group （routine culture），sh-NC group （with sh-NC transfected），sh-MANCR group （with sh-MANCR transfected），sh-MANCR + anti-NC group （with sh-MANCR and anti-NC both transfected），and sh-MANCR + anti-miR-150-5p group （with sh-MANCR and anti-miR-150-5p both transfected）. The mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin，N-cadherin，Vimentin， and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue，and the expression of miR-150-5p was lower than that in adjacent tissue （P<0.05）. Compared with that in GES-1，lncRNA MANCR expression in BGC-823 cells was increased （P<0.05）. Compared with those in the sh-NC group and control group，the EdU-positive cell rate，migration number，invasion number，the mRNA expressions of lncRNA MANCR and GPNMB， and the expressions of protein，N-cadherin protein， and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ，and the protein expressions of miR-150-5p and E-cadherin were higher （P<0.05）. Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group，the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate，migration number，invasion number，mRNA expressions of GPNMB， and expressions of protein，N-cadherin protein， and Vimentin protein were increased （P<0.05）. lncRNA MANCR could target the negative regulation of miR-150-5p，and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation，migration， and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.

[摘 要] 目的：探究环状RNA肌动蛋白束蛋白1（circFSCN1）调节miR-429/非转移性黑色素蛋白B（GPNMB）轴对胃癌细胞恶性生物学行为的影响及机制。方法：收集2022年9月至2023年9月期间在河北医科大学第一医院手术切除的54例胃癌组织及相应癌旁组织，用qPCR法检测胃癌组织中circFSCN1、miR-429和GPNMB mRNA的表达。常规培养胃癌细胞MGC803，将其分为对照组、sh-NC组、sh-circFSCN1组、sh-circFSCN1 + anti-NC组、sh-circFSCN1 + anti-miR-429组。qPCR法各组MGC803细胞中circFSCN1、miR-429和GPNMB mRNA的表达。CCK-8法、克隆形成实验、Transwell实验和流式细胞术分别检测各组MGC803细胞的增殖、迁移、侵袭和凋亡。免疫荧光法检测各组细胞中GPNMB蛋白的表达。WB法检测各组MGC803细胞中PCNA、MMP-2、GPNMB、cleaved caspase-3蛋白的表达。双萤光素酶报告基因实验和RNA结合蛋白免疫共沉淀（RIP）实验验证circFSCN1与miR-429和miR-429与GPNMB之间的结合调控关系。结果：circFSCN1、GPNMB mRNA在胃癌组织中均呈高表达（均P < 0.05），miR-429呈低表达（P < 0.05）。敲减circFSCN1可促进miR-429表达，抑制GPNMB mRNA表达，抑制miR-429则可促进GPNMB mRNA表达。敲减circFSCN1可显著抑制MGC803细胞的增殖、迁移、侵袭能力，并促进其凋亡，抑制miR-429可部分逆转敲减circFSCN1的作用。敲减circFSCN1可抑制MGC803细胞中PCNA、MMP-2和GPNMB蛋白表达，抑制cleaved caspase-3蛋白表达，抑制miR-429可部分逆转敲减circFSCN1的作用。circFSCN1与miR-429和miR-429与GPNMB mRNA之间存在靶向结合负向调控关系。结论：敲减circFSCN1通过miR-429/GPNMB轴抑制胃癌细胞的恶性生物学行为，circFSCN1是胃癌潜在的治疗靶点。

[摘 要] 目的：探究长链非编码RNA00894（LINC00894）调节微小RNA-205-5p（miR-205-5p）/糖蛋白非转移性黑色素瘤蛋白B（GPNMB）轴对胃癌细胞恶性生物学行为的影响。方法：收集2022年11月至2023年9月在河北医科大学第一医院手术切除的25例胃癌组织及相应癌旁组织，常规培养BGC823细胞，随机将其分为对照组、sh-NC组、sh-LINC00894组、sh-LINC00894 + anti-NC组、sh-LINC00894 + anti-miR-205-5p组，用转染试剂将相应质粒转染至各组细胞中。qPCR法检测各组BGC823细胞和癌组织中LINC00894、miR-205-5p和GPNMB mRNA表达，双萤光素酶报告基因实验和AGO2-RNA免疫共沉淀验证LINC00894与miR-205-5P和miR-205-5p与GPNMB间的靶向结合关系。克隆形成实验、EdU染色、划痕愈合实验和Transwell实验分别检测各组细胞的增殖、迁移和侵袭能力。WB法检测各组细胞中CDK1、MMP-2和MMP-9蛋白的表达。裸鼠移植瘤实验检测敲减LINC00894对移植瘤生长的影响，免疫组化法检测移植瘤组织中GPNMB蛋白的表达。结果：胃癌组织和细胞中LINC00894、GPNMB呈高表达，miR-205-5p呈低表达（均P < 0.05）。LINC00894与miR-205-5p和miR-205-5p与GPNMB之间存在靶向结合负向调控关系（均P < 0.05）。敲减LINC00894可促进BGC823细胞中miR-205-5p表达并抑制GPNMB表达（均P < 0.05），敲减LINC00894可抑制BGC823细胞的增殖、迁移和侵袭能力，以及抑制CDK1、MMP-2和MMP-9蛋白的表达（均P < 0.05），抑制miR-205-5p则可逆转此作用（均P < 0.05）。敲减LINC00894可抑制BGC823细胞移植瘤的生长、促进miR-205-5p表达、抑制GPNMB蛋白表达（均P < 0.05）。结论：在胃癌组织及细胞中LINC00894呈高表达，miR-205-5p呈低表达，敲减LINC00894表达可调控BGC823细胞中miR-205-5p/GPNMB通路蛋白表达并抑制其恶性生物学行为。

Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

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

ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Jieyu Formula （左归降糖解郁方， ZJJF） for diabetic rats with depression. MethodsSixty rats were randomly divided into normal group， model group， wingless MMTV integration site family member 5a （Wnt5a） agonist group， ZJJF group， and ZJJF plus Wnt5a inhibitor group， with 12 rats in each group. Except for the normal group， the rats were fed with high-fat chow， streptozotocin injection， and chronic mild unpredictable stress combination， to establish model of diabetes mellitus complicated with depression. After successful modelling， rats in the Wnt5a agonist group were given bilateral hippocampal stereotactic injections of Wnt5a agonist Foxy-5 with 5 μl each for 7 consecutive days； rats in ZJJF group were given 20.52 g/（kg·d） of ZJJF by gavage； rats in ZJJF plus Wnt5a inhibitor group were given the drug by gavage， and bilateral hippocampal stereotactic injections of Wnt5a inhibitors Box5， with the same dosage and injection method as above. The normal group and model group were given 10 ml/（kg·d） of normal saline by gavage. All groups were gavaged for 4 consecutive weeks. At the end of the intervention， the depression-like behaviour of rats was evaluated using the forced swimming experiment （immobility time） and the absent field experiment （number of activities）； the blood glucose and insulin levels of rats were measured and the insulin resistance index was calculated； the dendritic morphology of dentate gyrus neurons in the hippocampus was observed using Golgi staining； the level of dentate gyrus neuron proliferation was measured using 5-bromodeoxyuracil nucleoside （Brdu） injection and immunofluorescence； RT-qPCR and Western blot were used to detect the mRNA and protein expression of Wnt5a， Ras homologue genomic member A （RhoA） and Rho homologue-associated coiled-coil protein kinase 1 （ROCK1） in the dentate gyrus. ResultsCompared with the normal group， rats in the model group had significantly higher blood glucose， insulin and insulin resistance indices， longer immobility time， fewer activities， lower Brdu integral optical density values and Wnt5a， RhoA， ROCK1 protein and mRNA expression in the dentate gyrus of the hippocampus （P＜0.05 or P＜ 0.01）； the dendritic branches of rat hippocampal dentate gyrus neurons could be seen to be significantly reduced or broken， and their length shortened. Compared with the model group， the blood glucose， insulin and insulin resistance indices of rats in ZJJF group and the ZJJF plus Wnt5a inhibitor group significantly reduced （P＜0.05 or P＜0.01）； the immobility time of rats in the Wnt5a agonist group and ZJJF group was significantly shortened， the number of activities increased， the Brdu integral optical density values elevated， and the Wnt5a， RhoA， ROCK1 protein and mRNA expression elevated （P＜0.05 or P＜0.01）， and the number of dendritic branches of hippocampal dentate gyrus neurons significantly increased， the length lengthened， and the complexity of dendrites increased. Compared with the Wnt5a agonist group， rats in the ZJJF group showed significant decrease in blood glucose， insulin and insulin resistance indices， prolongation of immobilisation time， reduction in the number of activities， and reduction in the Brdu integral optical density value； except for the Wnt5a mRNA in ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression reduced in both ZJJF group and ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. Compared with ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression were reduced in ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. ConclusionZJJF can improve hyperglycemia and depressive-like behaviours in rat models of diabetes with depression， and its antidepressant effects may be related to the activation of hippocampal Wnt5a/RhoA signaling and promotion of dentate gyrus neuron dendritic growth.

Objective To evaluate the prognostic value of radiation-induced lymphocytopenia in the survival of patients with primary hepatocellular carcinoma receiving radiation therapy. Methods The clinical data of 98 patients with unresectable primary hepatocellular carcinoma who received radiotherapy were retrospectively analyzed. The minimum absolute lymphocyte count (min ALC) was graded in accordance with CTCAE V4.0. The optimal threshold of min ALC for prognosis was calculated by using the receiver operating characteristic curve, and the correlation of min ALC with clinical characteristics and dosimetry parameters was analyzed. The Kaplan-Meier method was employed to analyze the survival of patients with different levels of min ALC. Univariate and multivariate Cox proportional regression models were applied to analyze prognostic factors. Results The baseline and min ALC of 98 patients during radiotherapy were 1.52×10⁹/L and 0.45×10⁹/L, respectively(P<0.001). The optimal cut-off value of min ALC for the prediction of the one-year survival rate was 0.38×10⁹/L. GTV, the mean dose of the liver and spleen, the V5 and V10 of the liver and spleen, and the V15 of the spleen were correlated with min ALC, and the V5 of the liver was an independent predictor of min ALC. The overall survival of patients with high min ALC was higher than that of patients with low min ALC. Independent prognostic factors were min ALC≤0.38×10⁹/L (HR=0.515, P=0.024), min ALC≥grade 3 (HR=0.576, P=0.032), tumor thrombus in the portal/vena cava, Child-Pugh grade A, increase of ≥2 points in the Child-Pugh score after radiotherapy, and received more than two other therapies. Conclusion Min ALC≤0.38×10⁹/L and min ALC≥grade 3 have independent prognostic value in patients with unresectable hepatocellular carcinoma receiving radiotherapy.

Objective:To explore the application effect of rotating skin flap in the repair of skin and soft tissue defects in the perineum.Methods:A retrospective analysis was conducted on the data of 9 patients with perineal soft tissue defects treated in the Department of the First Affiliated Hospital, Wenzhou Medical University from January 2022 to March 2024. Among them, 8 cases were soft tissue defects after extensive resection of Paget′s disease in the perineum, and 1 case was soft tissue defects after treatment of severe urethral stricture. The defect area ranged from 4 cm×1.5 cm to 30 cm×35 cm, and all wounds were repaired with rotating skin flaps, For patients with excessive area, rotating skin flaps were used to cover important areas, combined with autologous skin and artificial skin to cover the remaining wounds. Patients with urethral stricture were treated with free oral mucosal reconstruction of the urethra combined with rotational skin flap coverage. The donor site was directly sutured or autologous skin was transplanted.Results:After surgery, the recipient skin flaps of 9 patients survived and the donor area healed. After a follow-up of 9-15 months, the skin flap survived well, with skin color approaching normal, and the donor site wound healed well. Eight patients with Paget′s disease did not show any recurrence, among which one patient with extensive wound expansion had good recovery of the perineal skin flap coverage area, and small-scale chronic ulcers appeared in the skin graft area. The skin flap of the patient with urethral stricture had recovered well, and the shape of the penis was good, without any urethral stricture, urinary fistula, sinus tract, etc.Conclusions:The rotational skin flap has a clear therapeutic effect on perineal soft tissue defects and is suitable for repairing perineal skin and soft tissue defects.

Objective To observe the protective effect of modified Baishile Decoction on hippocampal neuronal cells cultured in vitro;To explore its mechanism of treating post-stroke depression.Methods Hippocampal neuronal cells from mammary rats were isolated and cultured in vitro,cell injury was induced by oxygen glucose deprivation combined with lipopolysaccharide.The cells were divided into normal group,model group,blank serum group(10%)and modified Baishile Decoction containing serum group(10%).Invertedmicroscope was used to observe cell morphological changes,CCK-8 method was used to detect cell survival rate,Hoechst33342 staining was used to observe apoptosis,ELISA was used to detect Glu,5-HT,TNF-α,IL-1β,and IL-6 contents in cell supernatant,the expressions of purinergic P2X7 receptor(P2X7R)and NOD-like receptor protein 3(NLRP3)were detected by immunofluorescence staining.Results Compared with the normal group,the hippocampal neurons in the model group showed significant changes in cell morphology,the cell survival rate significantly decreased(P<0.01),the cell apoptosis increased(P<0.01);Glu,TNF-α,IL-1β,IL-6 contents in cell supernatant significantly increased(P<0.05,P<0.01),5-HT content significantly decreased(P<0.01),P2X7R and NLRP3 expressions in hippocampal neuronal cells significantly increased(P<0.01).Compared with the model group,the morphology of hippocampal neurons in modified Baishile Decoction containing serum group was significantly improved,the cell survival rate significantly increased(P<0.01),the cell apoptosis reduced(P<0.01);Glu,TNF-α and IL-1β content in cell supernatant significantly reduced(P<0.05,P<0.01),5-HT content significantly increased(P<0.01),and P2X7R and NLRP3 expressions in hippocampal neuronal cells significantly decreased(P<0.01).Conclusion Modified Baishile Decoction may exert a protective effect on oxidative glucose deprivation combined with lipopolysaccharide induced hippocampal neuronal inflammation damage by inhibiting the P2X7R/NLRP3 signaling pathway,regulating neurotransmitter secretion,and inhibiting inflammatory factor release,thus treating post-stroke depression.