1.Polypeptide-based Nanocarriers for Oral Targeted Delivery of CAR Genes to Pancreatic Cancer
Feng XIN ; Jian REN ; Zhao-Zhen LI ; Quan FANG ; Rui-Jing LIANG ; Lan-Lan LIU ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2026;53(2):431-441
ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.
2.Polypeptide-based Nanocarriers for Oral Targeted Delivery of CAR Genes to Pancreatic Cancer
Feng XIN ; Jian REN ; Zhao-Zhen LI ; Quan FANG ; Rui-Jing LIANG ; Lan-Lan LIU ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2026;53(2):431-441
ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.
3.Reliability and validation of the Adverse Childhood Experiences-International Questionnaire among men who have sex with men in China
Huifang XU ; Ying WANG ; Chenrui LI ; Ajuan LIANG ; Yong CAI
Shanghai Journal of Preventive Medicine 2025;37(10):878-883
ObjectiveThe significance of adverse childhood experiences (ACEs) among men who have sex with men (MSM) should not be overlooked. This study aims to assess the reliability and validity of the Chinese version of the Adverse Childhood Experiences-International Questionnaire (ACE-IQ) among the MSM population in China to evaluate its applicability in this group. MethodsA cross-sectional survey was conducted in three Chinese cities(Shanghai, Shenyang and Kunming) using snowball sampling, with a total of 1 130 MSM participants included. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess the structural validity of the scale. Internal consistency reliability was evaluated using Cronbach’s α coefficient, and split-half reliability was assessed with the Spearman-Brown coefficient. ResultsAccording to the EFA results, after removing item ACE10 (“parental death”), the 23-item ACE-IQ demonstrated a six-factor structure, including victimization or witnessing emotional/physical abuse, sexual abuse, physical neglect, family dysfunction, emotional neglect, and peer violence. CFA results indicated a good model fit for the six-factor model, supporting the EFA findings. The scale demonstrated good reliability, with a Cronbach's α coefficient of 0.852 and a Spearman-Brown coefficient of 0.899, indicating high internal consistency and split-half reliability within the studied population. ConclusionThe Chinese version of the ACE-IQ demonstrates satisfactory reliability and validity among MSM population, supporting its suitability for assessing ACEs in this group. The findings provide an empirical basis for subsequent mental health interventions.
4.Quality Evaluation of Zhuye Shigao Granules and Its Therapeutic Effect on Mice with Cold-dampness Pestilence Attacking Lung Syndrome
Haihong LI ; Jiaqi SHEN ; Liwen LIANG ; Ziqi YANG ; Yuting YANG ; Shuyun LIANG ; Zhiliang SUN ; Jiannan LI ; Guangzhi CAI ; Jiyu GONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):182-190
ObjectiveTo establish a quality evaluation method for Zhuye Shigao granules(Zhuye Shigaotang) based on fingerprint and determination of index components, and to investigate the therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome. MethodsThe fingerprint of Zhuye Shigao granules was established by high performance liquid chromatography(HPLC), and the methods for determination of total calcium, orientin, isoorientin, ginsenosides Rg1, Re and Rb1 and other 2 index components were established. Fifty ICR mice were randomly divided into the blank group, model group, Zhuye Shigao granules low, medium and high dose groups(9.3, 18.6, 37.2 g·kg-1·d-1), with 10 mice in each group. In addition to the blank group, the model mice with cold-dampness pestilence attacking lung syndrome was prepared by nasal drip of lipopolysaccharide combined with cold-dampness environment. Each administration group was given the corresponding liquid by gavage according to the dose, while the blank group and model group were given the same volume of normal saline by gavage. Then, the body temperature and organ index of mice in each group were measured, hematoxylin-eosin(HE) staining was used to investigate the lung tissue injury of mice in each group, and enzyme-linked immunosorbent assay(ELISA) was used to detect the changes of tumor necrosis factor-α(TNF-α), interleukin(IL)-lβ, IL-6, IL-10 levels in serum and lung tissue, as well as immunoglobulin(Ig)A and IgM levels in serum. ResultsThe fingerprint similarity of 10 batches of Zhuye Shigao granules was>0.950, and 20 common peaks were calibrated. Seven of them were identified, including peak 11(isoorientin), peak 12(orientin), peak 14(apioside liquiritin), peak 15(liquiritin), peak 17(apioside isoliquiritin), peak 19(isoliquiritin) and peak 20(liquiritigenin). The results of quantitative analysis showed that the content range of each index component in 10 batches of Zhuye Shigao granules was as follows:Total calcium of 9.978-11.294 mg·g-1, isoorientin of 0.033-0.041 mg·g-1, orientin of 0.046-0.055 mg·g-1, ginsenoside Rg1+ginsenoside Re of 0.748-0.762 mg·g-1, ginsenoside Rb1 of 0.151-0.197 mg·g-1, liquiritin of 1.106-1.366 mg·g-1, glycyrrhizic acid of 0.904-1.182 mg·g-1. Compared with the blank group, the body temperature of mice in the model group was significantly increased, the organ indexes of liver, lung and spleen were significantly decreased, the organ index of thymus was significantly increased, HE staining of lung tissue showed infiltration of inflammatory cells, a small amount of serous exudation was observed in the alveoli, and lung tissue was damaged. After the intervention of Zhuye Shigao granules, the pathological changes were improved compared with the model group. The expression levels of IL-1β, IL-6 and TNF-α were significantly increased, the expression level of IL-10 was significantly decreased in serum and lung tissue. The levels of IgA and IgM in serum were significantly decreased(P<0.01). Compared with the model group, the body temperature, the organ indexes and immune factor levels in serum and lung tissue of mice in the Zhuye Shigao granules medium and high dose groups were significantly reduced(P<0.05, P<0.01). ConclusionIn this study, the quality evaluation of Zhuye Shigao granules was carried out based on fingerprint combined with determination of index components, and the fingerprint of four herbs(Lophatheri Herba, Ophiopogonis Radix, Pinelliae Rhizoma and Glycyrrhizae Radix et Rhizoma) in this formula and the determination of 8 index components were established. The therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome may be related to inhibiting inflammatory response and mediating immune regulation.
5.Formononetin inhibits lipopolysaccharide-induced inflammation in nucleus pulposus mesenchymal stem cells
Qinghe YU ; Ziming CAI ; He TIAN ; Pian LI ; Ye RUAN ; Jinzhu LIANG ; Shuhui LIN ; Wenping LIN
Chinese Journal of Tissue Engineering Research 2025;29(25):5328-5334
BACKGROUND:Formononetin demonstrates potent anti-inflammatory and antioxidant abilities.However,its protective effect on nucleus pulposus mesenchymal stem cells is not yet clear.OBJECTIVE:To investigate the effect and mechanism of formononetin on nucleus pulposus mesenchymal stem cells under an inflammatory microenvironment.METHODS:(1)Primary nucleus pulposus mesenchymal stem cells were isolated from the intervertebral discs of SD rats,and flow cytometry was performed to identify the surface markers of mesenchymal stem cells.(2)The CCK-8 assay was employed to evaluate the impact of lipopolysaccharide and formononetin on the proliferation viability of nucleus pulposus mesenchymal stem cells,aiming to determine the appropriate concentration of formononetin for subsequent cell treatments.(3)An inflammatory microenvironment was simulated by adding 5 μg/mL lipopolysaccharide to the DMEM/F-12 culture medium,and nucleus pulposus mesenchymal stem cells were treated with different concentrations of formononetin for 24 hours.Levels of inflammation markers were detected using western blot assay,real-time quantitative PCR,and immunofluorescence.Western blot assay was conducted to measure the protein levels of the nuclear factor kappa B signaling pathway.RESULTS AND CONCLUSION:(1)The nucleus pulposus mesenchymal stem cells cultured in adherent wall were shuttle-shaped with good growth status.The results of flow cytometry showed that the surface markers of mesenchymal stem cells were positive for CD29,CD44,and CD90,and the surface markers of hematopoietic stem cells were negative for CD34 and CD45.(2)The treatment with formononetin at 12.5,25,50,100,and 200 μmol/L concentrations for 24 hours had no significant proliferation inhibitory effect on nucleus pulposus mesenchymal stem cells.Compared with the lipopolysaccharide group,the cell viability of nucleus pulposus mesenchymal stem cells treated with 12.5,25,and 50 μmol/L formononetin for 24 hours was significantly increased,so formononetin at 12.5,25,and 50 μmol/L concentrations was subsequently selected as the low,medium,and high concentrations for treating nucleus pulposus mesenchymal stem cells.(3)Compared with the lipopolysaccharide group,the protein and mRNA expressions of matrix metalloproteinase-3,matrix metalloproteinase-13,and tumor necrosis factor-α in nucleus pulposus mesenchymal stem cells in the low,medium,and high concentrations of formononetin groups were significantly decreased(P<0.05)in a dose-dependent manner.(4)Compared with the lipopolysaccharide group,the expressions of phosphorylated nuclear factor kappa B and phosphorylated nuclear factor kappa B inhibitor protein in nucleus pulposus mesenchymal stem cells in the low,medium,and high concentrations of formononetin groups were significantly decreased(P<0.05)in a dose-dependent manner.The above results suggest that formononetin may attenuate lipopolysaccharide-induced inflammation in rat nucleus pulposus mesenchymal stem cells by inhibiting the activation of the nuclear factor kappa B signaling pathway.
6.Comparison of short-term outcomes and 5-year overall survival between robotic and laparoscopic gastrectomy for gastric cancer
Li ZHANG ; Mingzhi CAI ; Bin LI ; Gang MA ; Xuejing ZHENG ; Ye TIAN ; Xuejun WANG ; Yong LIU ; Han LIANG
Chinese Journal of General Surgery 2025;40(8):601-606
Objective:To compare the short-term clinical outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) in treating gastric cancer, as well as the overall 5-year's survival rate.Methods:In this retrospective cohort study, 874 patients undergoing minimally invasive gastrectomy were recruited from Jan 2016 to Jan 2020 (LG: n=719; RG: n=155). A one-to-one propensity score matching analysis was applied to minimize the selection bias due to confounding factors, yielding 150 patients in each of the RG and LG groups. After matching, the short-term outcomes and 5-year overall survival were compared in the two groups. Results:The propensity score matching cohort analysis showed a similar 5-year overall survival between RG and LG groups ( P=0.235). Concerning the short-term outcomes, the RG compared to LG resulted in lower blood loss ( P=0.011), lower postoperative complications ( P=0.001), less postoperative pain ( P=0.014), earlier initiation of soft diet ( P=0.010), shorter hospital stay ( P=0.011), but higher hospitalization expenses ( P=0.004). Conclusions:RG had a similar overall survival outcome compared to LG while offering better safety and efficacy in terms of less blood loss, lower surgery complications, faster recovery, and less postoperative pain. Higher hospital expenses were the main disadvantage of RG that could limit its application.
7.A preliminary exploration of clinical practice in 5G-ultra-long-distance robot-assisted liver resection
Xiao LIANG ; Zefeng SHEN ; Yuxin FAN ; Yangyang XIE ; Ren′an JIN ; Mingyu CHEN ; Zheyong LI ; Xiujun CAI
Chinese Journal of Surgery 2025;63(6):508-514
Objective:To summarize the initial experience of 5G-ultra-long-distance robotic hepatectomy.Methods:This is a retrospective case series study. The clinical information from 5 cases of 5G ultra-long-distance robot-assisted hepatectomy performed was collected from June 2023 to October 2024, in collaboration between Sir Run Run Shaw Hospital, Zhejiang University School of Medicine in Hangzhou and Alaer Hospital, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine in Alaer, located 4 600 km apart. The patients comprised 1 male and 4 females, aged from 36 to 59 years, with an average age of 48 years. Their body mass index ranged from 20.4 to 30.9 kg/m2, with an average of 24.62 kg/m2. Preoperatively, 5 patients were diagnosed with liver disease requiring hepatectomy. The operations used 5G ultra-remote four-arm endoscopic robot surgery system. The remote control room was located in Sir Run Run Shaw Hospital (Hangzhou, Zhejiang), and the robot operating room was located in Alaer Hospital (Alaer, Xinjiang). The wired network relied on 60 Mb/s high-speed public Internet special line (China Telecom). In order to ensure the security of data transmission, the system implemented a double-layer encryption strategy for the wired network, and carried out strict debugging and verification for both the wired and wireless networks. Perioperative data and information on network performance were collected for 5 patients.Results:The surgical duration of the 5 cases of 5G ultra-long-distance robot-assisted hepatectomy ranged from 49 to 342 minutes, with an average of 184 minutes. Intraoperative blood loss varied from 5 to 800 ml, averaging 183 ml. Network performance was evaluated during the surgery, revealing an average network latency of 108.2 ms, with no significant lag or delay observed during any of the procedures. All patients recovered smoothly, with a postoperative hospital stay ranging from 5 to 10 days, averaging 7.2 days. Postoperative complications included 1 case of hypoproteinemia and 1 case of pleural effusion. Pathological examination confirmed that all cases suffered benign liver diseases (three patients with hepatic hemangioma, one with regenerative nodule in cirrhosis, and one with hepatolithiasis and choledocholithiasis).Conclusion:The preliminary exploration of clinical practice indicated that 5G-ultra-long-distance robot-assisted surgery is feasible for hepatectomy, with no severe complications affecting patients′ recovery.
8.Additional role of low-density lipoprotein cholesterol on the risk of osteoporosis in men with or without coronary heart disease: a real-world longitudinal study.
Jing ZENG ; Zi-Mo PAN ; Ting LI ; Ze-Yu CHEN ; Xiao-Yan CAI ; Mei-Liang GONG ; Xin-Li DENG ; Sheng-Shu WANG ; Nan LI ; Miao LIU ; Chun-Lin LI
Journal of Geriatric Cardiology 2025;22(2):219-228
BACKGROUND:
Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.
METHODS:
The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model.
RESULTS:
During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437).
CONCLUSIONS
Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.
9.Buyang Huanwu Decoction Promotes Recovery after Spinal Cord Injury by Regulating cAMP/PKA/NF-κB p65 Pathway.
Si-Yuan LI ; Ting-Ting FAN ; Jian YIN ; Cai-Yun WAN ; Mei-Li LI ; Shuai-Shuai XIA ; Qiang LI ; Liang LI
Chinese journal of integrative medicine 2025;31(7):635-643
OBJECTIVE:
To investigate whether Buyang Huanwu Decoction (BYHWD) had a good curative effect on the neuroprotection of red nucleus neurons after spinal cord injury (SCI) and the possible molecular mechanism.
METHODS:
Ninety male Sprague-Dawley rats were divided into 5 groups (n=18 per group) according to a random number table, including the control, model, low- (12.78 g/kg, BL group), medium- (25.65 g/kg, BM group), and high-dose BYHWD groups (51.30 g/kg, BH group). A rubrospinal tract transection model in rats was established, and different doses of BYHWD were intragastrically administrated for 4 weeks. The forelimb locomotor function was recorded using the spontaneous vertical exploration test. Cyclic adenosine monophosphate (cAMP) level in red nucleus was detected through an enzyme-linked immunosorbent assay. The morphology and number of red nucleus neurons were observed using Nissl's staining and axonal retrograde tracing by Fluoro-Gold (FG). The expression of cAMP-dependent protein kinase A (PKA), nuclear factor kappa-B (NF-κB) p65, and brain-derived neurotrophic factor (BDNF) in red nucleus were detected using immunohistochemistry and quantitative real-time polymerase chain reaction.
RESULTS:
Compared with the control group, the utilization rate of bilateral forelimbs, unilateral right forelimbs, proportion of FG-labeled positive neurons, cAMP level, protein expressions of PKA and BDNF, and BDNF mRNA expression were significantly decreased in the model group (P<0.01), while NF-κB p65 was increased in the model group (P<0.01). Compared with the model group, the utilization rate of bilateral forelimbs and unilateral right forelimbs were significantly higher in the BL, BM and BH groups (P<0.01), the proportion of FG-labeled positive neurons, cAMP level, protein expressions of PKA and BDNF and BDNF mRNA expression in all BYHWD groups were increased (P<0.05 or P<0.01), while NF-κB p65 were decreased in all BYHWD groups (P<0.05 or P<0.01).
CONCLUSIONS
BYHWD possesses a sound neuroprotective effect on red nucleus neurons after SCI, and the efficacy was dose-related. The mechanism may be related to regulating the cAMP/PKA/NF-κ B p65 signaling pathway, finally promoting expression of BDNF.
Animals
;
Spinal Cord Injuries/pathology*
;
Drugs, Chinese Herbal/therapeutic use*
;
Rats, Sprague-Dawley
;
Male
;
Cyclic AMP/metabolism*
;
Transcription Factor RelA/metabolism*
;
Cyclic AMP-Dependent Protein Kinases/metabolism*
;
Signal Transduction/drug effects*
;
Brain-Derived Neurotrophic Factor/genetics*
;
Red Nucleus/metabolism*
;
Recovery of Function/drug effects*
;
Neurons/metabolism*
;
Rats
10.Clinical value of serum hsa_circRNA_0002980 and hsa_circRNA_104348 expression in diagnosis and prognosis evaluation of liver cancer patients
Dong LIU ; Qingshan CAI ; Shudong LI ; Jiaming LIANG
International Journal of Laboratory Medicine 2025;46(8):976-981
Objective To investigate the clinical value of serum hsa_circRNA_0002980 and hsa_circRNA_104348 expression in the diagnosis and prognosis evaluation of liver cancer patients.Methods From April 2020 to April 2022,a total of 105 liver cancer patients and 105 liver cirrhosis patients admitted in the hospital were selected as the liver cancer group and cirrhosis group,and another 105 healthy volunteers who underwent physical examinations in the hospital were selected as the control group.Real-time fluorescence quantitative PCR(qPCR)was applied to detect the expression of serum hsa_circRNA_0002980 and hsa_circRNA_104348.Receiver operating characteristic(ROC)curve was applied to evaluate the diagnostic value and prognostic val-ue of serum hsa_circRNA_0002980 and hsa_circRNA_104348 expression in liver cancer.Multivariate COX re-gression was performed to analyze the influencing factors of prognosis in liver cancer.Results The expression levels of serum hsa_circRNA_0002980 in the liver cancer group,liver cirrhosis group,and control group in-creased sequentially(P<0.05),while the expression levels of serum hsa_circRNA_104348 decreased sequen-tially(P<0.05).The levels of alanine aminotransferase and aspartate aminotransferase in the liver cancer group and the liver cirrhosis group were higher than those in the control group(P<0.05),and the level of al-bumin was lower than that in the control group(P<0.05).The area under the curve(AUC)for the diagnosis of liver cancer by hsa_circRNA_0002980 combined with hsa_circRNA_104348 was 0.888(95%CI:0.838-0.928),which was obviously higher than those of hsa_circRNA_0002980(Z=3.526,P<0.001)and hsa_cir-cRNA_104348 alone(Z=2.184,P=0.029).The expression level of serum hsa_circRNA_0002980 in the poor prognosis group was lower than that in the good prognosis group(P<0.05),and the expression level of ser-um hsa_circRNA_104348 and the proportion of TNM stage Ⅲ+Ⅳ were higher than those in the good progno-sis group(P<0.05).The AUC for predicting prognosis in liver cancer patients by the combination of hsa_cir-cRNA_0002980 and hsa_circRNA_104348 was 0.870(95%CI:0.790-0.928),and there was no statistically significant difference compared to the AUC predicted separately by hsa_circRNA_0002980 and hsa_circRNA_104348(P>0.05).The expression of serum hsa_circRNA_0002980,hsa_circRNA_104348 and TNM stage were influencing factors for the prognosis of liver cancer patients(P<0.05).Conclusion The expression lev-el of hsa_circRNA_0002980 in the serum of liver cancer patients is relatively low,while the expression level of hsa_circRNA_104348 is relatively high.Both have certain clinical significance in the diagnosis and prognosis e-valuation of liver cancer.

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