Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

OBJECTIVE: To observe the clinical efficacy of electroacupuncture combined with ear tip bloodletting for insomnia with phlegm-fire disturbing heart. METHODS: A total of 60 cases with insomnia of phlegm-fire disturbing heart were selected, and the treatment of electroacupuncture combined with ear tip bloodletting was delivered. Acupuncture was applied at Yintang (GV24⁺), Shenting (GV24), Sishencong (EX-HN1) and bilateral Shenmen (HT7), Quchi (LI11), Zhaohai (KI6), Shenmai (BL62), Fenglong (ST40), Neiting (ST4), Yintang (GV24⁺) and Shenting (GV24) were connected to electroacupuncture, continuous wave, 2 Hz in frequency. In addition, bloodletting was applied at ear tip. The treatment was given for 4 weeks. Before treatment, and after 1,4 weeks into treatment, the scores of Pittsburgh sleep quality index (PSQI), Athens insomnia scale (AIS), insomnia severity index (ISI) and TCM syndrome were compared, and the clinical efficacy was evaluated in the patients. RESULTS: After 1,4 weeks into treatment, the scores of PSQI, AIS, ISI and TCM syndrome were decreased compared with those before treatment in the patients (P<0.05). Of 60 cases, 30 cases were cured, 19 cases markedly effective, 9 cases effective and 2 cases failed, and the total effective rate was 96.7% (58/60). CONCLUSION Electroacupuncture combined with ear tip bloodletting can improve the sleep quality and clinical symptoms in patients with insomnia of phlegm-fire disturbing heart.
Humans ; Male ; Female ; Electroacupuncture ; Middle Aged ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Adult ; Bloodletting ; Acupuncture Points ; Aged ; Combined Modality Therapy ; Treatment Outcome ; Young Adult

Volumes 9 and 10 of Sun Simiao's Supplement to Important Formulas Worth a Thousand Gold Pieces record part of Trea-tise on Cold Damage,which contain Sun Simiao's unique thoughts on six-meridian treatment.Sun Simiao's treatment of Taiyang me-ridian emphasizes the classification of prescriptions and syndromes,advocates the correct treatment methods,and establishes three guidelines;Yangming meridian emphasizes the differentiation of cold and heat syndromes;except Taiyang meridian,all meridians em-phasize the differentiation of outline syndromes.It has made important contributions to the inheritance and development of the six-me-ridian thought of Treatise on Cold Damage in later generations.

Acupuncture is considered both safe and effective for treating depression;however,its underlying mechanism remains incompletely understood.This article reviewed the mechanisms of acupuncture in depression from the perspective of brain network dynamics.It has been found abnormal alterations in the structural and functional brain networks,including the default mode network,cognitive control network,salience network and affective network in individuals with depression.Acupuncture has been shown to enhance the diffusion anisotropy value of white matter and repair the microstructure of white matter fiber bundles in key brain regions.It can also modulate the activation the functional brain networks,either globally or in specific network segments,improve functional connectivity within and between functional networks,regulate global transmission efficiency and connectivity patterns of functional networks,restore brain network interaction balance,regulate abnormal integration of functional networks,and improve emotional regulation ability and cognitive function,in order to alleviate the clinical symptoms of depression and serve as an effective antidepressant therapy,which can provide reference for the study of acupuncture intervention in the brain network mechanism of depression.

In order to investigate the mitigating effect of Yin Chen aqueous extract on liver injury induced by LPS combined with D-GalN in mice,a mouse liver injury model was established by in-traperitoneal injection of LPS and D-GalN,and the mice were group-fed by instillation of saline,bi-phenyl dibenzyl ester,and Yin Chen aqueous extract with different concentrations of LPS and D-GalN.The liver index of mice was calculated,pathological tissue sections were observed,and the expression of ALT,AST,inflammatory cytokines,oxidative stress,hepatic enzymes,and IL-17/TNF pathway were detected in serum to investigate the effects and mechanisms of the aqueous ex-tracts of Yin Chen in alleviating the liver injury in mice.The results showed that the liver index of mice in the model group was significantly elevated,the serum levels of ALT and AST were signifi-cantly elevated,the levels of IL-iβ,IL-8 and TNF-α in liver tissue were significantly elevated,the levels of IL-4 were significantly reduced,the levels of GSH-Px,CAT and SOD were significantly reduced,the levels of ROS and MDA were significantly elevated,CYP2E1 and CYP1A2 protein content and mRNA expression were significantly up-regulated,and the expression levels of TNF,TNFR1,IL-17A,ACT1 and IL-6 mRNA were significantly up-regulated.The study showed that the aqueous extract of Yin Chen had a certain alleviating effect on the liver injury caused by LPS combined with D-GalN in mice.The mechanism of action includes decreasing the metabolic level of hepatic drug enzymes,alleviating oxidative stress,inhibiting the expression of IL-17/TNF pathway and down-regulating the level of inflammatory factors in mice.

Bisphenol A(BPA)is an environmental endocrine disruptor commonly found in industri-al products such as plastics,resin coatings,and paper coatings,and it poses potential reproductive hazards.Despite extensive research,studies examining its effects on the F1 generation of rabbits are limited.This study established a BPA exposure model in pregnant female rabbits to investigate its impact on reproductive hormones,apoptosis,oxidative stress,inflammatory responses,and tissue integrity in weaned female offspring.The results indicate that BPA exposure induces oxidative stress and inflammation in F1 rabbits,disrupts hormonal balance,and affects antioxidant enzymes and inflammatory mediators through the modulation of the Nrf2 and NF-κB signaling pathways,ultimately leading to apoptosis and tissue damage.

Objective To establish orthotopic and ectopic pancreatic cancer models in C57BL/6N mice with normal immune function using in vivo imaging technology for visual characterization.Methods Orthotopic and ectopic pancreatic cancer models were established in Kunming mice by injecting a small volume of cell suspension containing firefly luciferase-expressing Panc02-luciferase pancreatic cancer cells into the head of the pancreas or the right axillary region.In vivo imaging technology was used to optimize the modeling method and timing in Kunming mice.Subsequently,the same method was applied to C57BL/6N mice using wild-type Panc02 pancreatic cancer cells to establish orthotopic and ectopic pancreatic cancer models with intact immune function.Key parameters,including body weight,inoculation positive rate,tumor growth time,tumor volume,and pathological characteristics across different organs,were compared be-tween the orthotopic and ectopic models in C57BL/6N mice to evaluate the applicability of these models.Results Both the small animal in vivo imaging experiments in Kunming mice and the tumor growth observation in C57BL/6N mice demonstrated that the construction periods for orthotopic and ectopic pancreatic cancer models were 20 days,with survival rates exceeding 90%.The inoculation positive rates in C57BL/6N mice were 92.3%for the orthotopic model and 78.6%for the ectopic model.On day 20 post-inoculation,the tumor volumes were(117.04±109.56)mm3 for the orthotopic model and(155.68±168.73)mm3 for the ectopic model,indicating high model success rates and consistent tumor growth.HE staining revealed pathological mitotic figures and poorly differentiated tumor tissues in both models of C57BL/6N mice,with no evidence of metastasis to other organs.Conclusions Orthotopic and ectopic pancreatic cancer models in immu-nocompetent mice were successfully developed in this study,mimicking early-stage pancreatic cancer characteristics.These models pro-vide a reliable platform for screening early diagnostic biomarkers and evaluating therapeutic interventions for pancreatic cancer.

BACKGROUND:The incidence of inflammatory bowel disease has been steadily rising,accompanied by a lack of definitive therapeutic strategies.Recent research endeavors have illuminated the promising potential of mesenchymal stem cells in mitigating the symptoms of inflammatory bowel disease,offering a glimmer of hope for afflicted patients.OBJECTIVE:To review the mechanisms of action of mesenchymal stem cells derived from various sources in the management of inflammatory bowel disease,aiming to provide insights for future research endeavors.METHODS:Utilizing the keywords"mesenchymal stem cells,MSCs,exosomes,extracellular vesicles,EVs,inflammatory bowel disease,IBD,ulcerative colitis,UC,Crohn's disease,CD"in English and their Chinese equivalents in CNKI and PubMed databases,a total of 89 eligible articles were selected for this review.RESULTS AND CONCLUSION:Currently,six types of mesenchymal stem cells are being explored for inflammatory bowel disease therapy:bone marrow-derived mesenchymal stem cells,adipose tissue-derived mesenchymal stem cells,perinatal tissue-derived mesenchymal stem cells,induced pluripotent stem cell-derived mesenchymal stem cells,embryonic stem cell-derived mesenchymal stem cells,and gingival mesenchymal stem cells.Five administration routes have been adopted,with intravenous and intraperitoneal injections being the most prevalent,followed by local,mesenteric,and intra rectal injections.Their therapeutic mechanisms encompass differentiation,regeneration,anti-inflammatory effects,immune modulation,neuroprotection,antioxidant stress response,homing,modulation of gut microbiota,autophagy,ferroptosis,and endoplasmic reticulum stress.While sharing functional similarities,mesenchymal stem cells from different sources exhibit unique characteristics that confer them with distinct advantages and therapeutic potentials.Nevertheless,research into the specific properties of these mesenchymal stem cells remains limited,necessitating deeper exploration of their nuanced differences to optimize their therapeutic efficacy in inflammatory bowel disease.Additionally,the clinical safety of mesenchymal stem cells-based therapies warrants further observation and evaluation.

Objective:To investigate the role and molecular mechanism of dual-specificity phosphatase 26(DUSP26)in the proliferation,migration and invasion of lung adenocarcinoma(LUAD)A549 cells.Methods:The expression profile of DUSP26 was retrieved from the GEPIA2 tumor database,and its differential expression in LUAD tissues and normal human lung tissues were analyzed.Twelve pairs of LUAD tissue and paracancerous tissue surgically resected at Pingxiang People's Hospital between October 2022 and October 2023 were collected.The difference in DUSP26 expression between LUAD tissues and paracancerous tissues was analyzed using immunohistochemical(IHC)staining and Western blotting(WB).Additionally,the expression of DUSP26 in four LUAD cells(A549,SK-LU-1,Calu-3,H1299)and two normal bronchial epithelial cells(BEAS-2B,HBEC)was detected using WB method.A549 cells stably overexpressing DUSP26(DUSP26-OE)or corresponding negative control(DUSP26-OENC)were constructed via lentiviral transfection.The effects of DUSP26 overexpression on cell proliferation,migration and invasion were detected using colony formation,scratch assay,and Transwell chamber assay,respectively.The expression levels of TGF-β1/SMAD2/3 pathway-and epithelial-mesenchymal transition(EMT)-related proteins were detected using WB method,and the expression levels of Ki-67 and cyclin D1 in cells were detected by immunofluorescence staining.Rescue experiments were conducted by adding 5 ng/mL recombinant TGF-β1.A nude mouse xenograft model was established using A549 cells to observe the effect of DUSP26 overexpression on the in vivo growth of transplanted tumors.The expression levels of TGF-β1/SMAD2/3 pathway-and EMT-related proteins in transplanted tumor tissues were assessed using WB method,and the expression levels of Ki-67 and cyclin D1 in transplanted tumor tissues were detected using immunofluorescence staining.Results:DUSP26 expression was downregulated in both LUAD tissues and cells(P<0.05,P<0.01,P<0.001 or P<0.000 1).Compared with the DUSP26-OENC group,the DUSP26-OE group showed significantly reduced proliferation,migration and invasion of A549 cells(P<0.01 or P<0.001).Furthermore,the protein levels of TGF-β1,p-SMAD2/3,vimentin,N-cadherin,snail,Ki-67,and cyclin D1 were significantly reduced(P<0.01,P<0.001 or P<0.000 1),while E-cadherin level was increased in the DUSP26-OE group(P<0.000 1).The addition of 5 ng/mL TGF-β1 recombinant protein partially reversed the effects of DUSP26 overexpression in vitro experiments.The nude mice A549 cell xenograft model was successfully constructed.The growth rate of transplanted tumors was significantly slower in the DUSP26-OE group,with reduced volume and mass(all P<0.001).The protein levels of TGF-β1,p-SMAD2/3,vimentin,N-cadherin,snail,Ki-67,and cyclin D1 in the transplanted tumor tissues were all reduced(P<0.01 or P<0.001),while E-cadherin level was increased(P<0.000 1).Conclusion:DUSP26 is downregulated in both LUAD tissues and cells.Upregulation of DUSP26 suppresses the proliferation,migration and invasion of A549 cells by inhibiting the TGF-β1/SMAD2/3 signaling pathway.

Objective:To investigate the effects of a matrix metalloproteinase(MMP) inhibitor (ilomastat, GM6001) on learning and memory function and hippocampal myelin-related proteins in epileptic model rats.Methods:Thirty 8-week-old male SPF Sprague-Dawley rats were randomly divided into control group, intervention control group, short-term model group, long-term model group and long-term intervention group, with 6 rats in each group.The lithium-pilocarpine method was used to induce status epilepticus (SE). SE was terminated respectively by intraperitoneal injection of diazepam(10 mg/kg) at 15 min in short-term model group and at 30 min both in the long-term model group and long-term intervention group. Rats in intervention control group and long-term intervention group were treated with GM6001 (20 μg/kg) via tail vein injection. Morris water maze test was used to assess the learning and memory function and the blood-brain barrier permeability was evaluated by Evans blue (EB) staining. The levels of serum MMP, the hippocampal myelin basic protein (MBP) and 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) were measured by ELISA and Western blot.Statistical analysis was performed by SPSS 21.0 software, with repeated measures ANOVA for Morris water maze data and one-way ANOVA with LSD post hoc test for other comparisons.Results:(1) In the water maze test, the interaction between the time and group on the latencies reached to the platform showed no significance among the 5 groups of rats ( F=0.430, P=0.970). The main effects of time and group on latencies were both significant among the 5 groups( F=144.521, 12.819, both P<0.001).From the second day to the fifth day, the latencies reached to the platform of rats in the long-term model group were significantly higher than those in the control group and in the long-term intervention group (both P<0.05). There were statistically significant differences in the latency of the first time reached the platform, the duration in the target quadrant, the frequency of crossing the platform and the distance to the platform among the 5 groups ( F=7.008, 7.306, 15.704, 11.559, all P<0.05). In the long-term intervention group, the latency of the first time reached the platform ((13.71±4.41) s) and the distance to the platform ((60.37±8.59) cm) were significantly lower than those in the long-term model group ((23.52±5.34) s, (73.06±12.01) cm) (both P<0.05), and the duration in the target quadrant ((10.93±2.99) s) and the frequency of crossing the platform (2.00(1.75, 2.75)times) were significantly higher than those of the long-term model group ((6.04±4.33) s, 1.00(0, 1.00)times) (both P<0.05).(2) The hippocampal EB fluorescence intensity and the serum levels of MMP-2 and MMP-9 were significantly different among the 5 groups ( F=15.249, 7.951, 33.299, all P<0.001). The EB fluorescence intensity of the long-term model group ((0.18±0.03) /100 μm 2) was significantly higher than that in control group ((0.09±0.02) /100 μm 2) and the long-term intervention group ((0.12±0.04) /100 μm 2) (both P<0.05). The serum MMP-2 and MMP-9 levels in the long-term model group ((10.91±1.36) ng/mL, (10.96±1.28) ng/mL) were significantly higher than those of the control group ((7.89±1.04) ng/mL, (4.20±1.48) ng/mL) and the long-term intervention group ((6.49±1.12) ng/mL, (8.06±0.91) ng/mL) (all P<0.05). (3) The expression levels of hippocampal MBP and CNPase were significantly different among the 5 groups ( F=8.757, 4.116, both P<0.05). The expression levels of MBP and CNPase in long-term model group ((1.00±0.19), (0.93±0.21)) were significantly lower than those in the control group ((1.57±0.27), (1.36±0.22)) and the long-term intervention group ((1.45±0.19), (1.23±0.26)) (all P<0.05). Conclusion:The MMP inhibitor GM6001 can ameliorate learning and memory deficits in epileptic model rats, potentially by reducing blood-brain barrier permeability and alleviating hippocampal myelin damage.