1.Expression and Clinical Significance of PLCβ4 Gene in Hepatocellular Carcinoma Analyzed Based on TCGA Database and Experimental Validation
Limei WEN ; Yali GUO ; Qiang HOU ; Dongxuan ZHENG ; Wu DAI ; Xiang GAO ; Jianhua YANG ; Junping HU
Cancer Research on Prevention and Treatment 2025;52(6):502-510
Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.
2.Efficiency and safety of belimumab in the treatment of lupus nephritis in Chinese adults:a meta-analysis
Bojiang LI ; Hongxia PAN ; Yixing FU ; Meirong FANG ; Xiang HU ; Jianhua DONG ; Youwen XIAO
China Pharmacy 2024;35(7):853-859
OBJECTIVE To systematically evaluate the real-world effectiveness and safety of belimumab in the treatment of lupus nephritis (LN) in Chinese adult patients. METHODS Retrieved from PubMed, Embase, Web of Science, Cochrane Library, Wanfang data, CNKI, VIP and CBM, real-world studies on belimumab in the treatment of LN in Chinese adult patients were collected from the inception to July 7th, 2023. Two reviewers independently screened the literature, extracted data, and assessed the quality of the included studies. Meta-analysis was then performed using RevMan 5.3 software. RESULTS A total of 10 real- world studies were included, involving 253 Chinese adult patients with LN. The results of the meta-analysis demonstrated that the complete renal response rate, partial renal response rate, and the incidence of adverse reaction rate in Chinese adult patients with LN treated with belimumab were 61% (95%CI was 46%-76%, P<0.000 01), 23%(95%CI was 2%-44%, P=0.03), and 30% (95%CI was 16%-43%, P<0.000 01), respectively. Belimumab could reduce the 24-hour urinary protein (MD=-1.71, 95%CI was -3.02--0.40, P=0.01), urine protein-creatinine ratio (MD=-1.76,95%CI was -2.06--1.46,P<0.000 01), the systemic lupus erythematosus disease activity index (MD=-8.63, 95%CI was -12.12--5.13, P<0.000 01), and glucocorticoids dosage (MD=-18.65, 95%CI was -31.82--5.48, P=0.006). In addition, it could elevate the levels of complement C3 (MD=0.19, 95%CI was 0.08-0.30, P=0.000 6) and complement C4 (MD=0.06, 95%CI was 0.02-0.09, P=0.001). However, belimumab could not improve the levels of serum creatinine and estimated glomerular filtration rate (P>0.05). CONCLUSIONS Belimumab has good efficacy and safety in Chinese adult patients with LN.
3.Attenuation and synergism of Hugan buzure recipe combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism
Xiaoyi MENG ; Jianhua YANG ; Limei WEN ; Tuerhong AYIZIBA ; Junping HU
China Pharmacy 2024;35(3):283-289
OBJECTIVE To investigate the attenuation and synergism of Hugan buzure recipe (HBR) combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism. METHODS Eight nude mice were selected from 40 nude mice as the blank group (normal saline), and the remaining nude mice were inoculated with hepatoma cells Huh7 to establish the tumor-bearing model. The 32 modeled nude mice were randomly allocated to four groups: model group (normal saline, ig), HBR group (0.69 g/kg, ig), oxaliplatin group (10 mg/kg, ip), and combination group (intraperitoneal injection of 0.69 g/kg HBR+intragastric administration of 10 mg/kg oxaliplatin), with 8 mice in each group. Administer drug/normal saline once a day for 32 consecutive days; administer subcutaneous injection once every 7 days for a total of 5 times. During the experiment, the general condition of nude mice in each group was observed, and the tumor volume was measured every 4 days. On the 30th day of administration, the thermal stimulation paw withdrawal latency of nude mice in each group were detected. The tumor inhibition rate, spleen coefficient, the number of red blood cells, white blood cells and platelets in the whole blood of nude mice in each group, and the content of aspartate aminotransferase (AST) and creatinine in serum were detected after the end of administration. HE staining was used to observe the pathological changes in tumor tissues in nude mice in each group. The expression of microtubule-associated protein 1 light chain 3 (LC3),selective autophagy adaptor protein p62, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), and Caspase-3 protein in tumor tissues. RESULT Compared with the model group, the tumor volume, tumor weight, white blood cells,red blood cells in the whole blood and spleen coefficients of nude mice in the oxaliplatin group were significantly decreased (P<0.01); the thermal stimulation paw withdrawal latency, AST and creatinine in serum were significantly increased (P<0.05 or P<0.01). Compared with the oxaliplatin group, the tumor volume and tumor weight of nude mice in the combination group were significantly decreased (P<0.01); the white blood cells, red blood cells and platelets in the whole blood and spleen coefficients of nude mice were significantly increased (P<0.05 or P<0.01); the thermal stimulation paw withdrawal latency, AST and creatinine in serum were significantly decreased (P<0.01); the expression levels of LC3, Bax and Caspase-3 proteins in tumor tissues of nude mice were significantly increased (P<0.01), and the expression levels of p62 and Bcl-2 proteins were significantly decreased (P<0.01). CONCLUSIONS HBR enhances the tumor inhibition rate of oxaliplatin by inducing apoptosis and autophagy, and can alleviate the peripheral neurotoxicity, hematological toxicity, hepatorenal toxicity, and immune organ toxicity caused by oxaliplatin in nude mice.
4.BMI1/NF-κB axis remodeling TAMs phenotype promotes the malignant biological behavior of oral squa-mous cell carcinoma
Yahui LI ; Huan LI ; Yaodong HE ; Rong LIU ; Junhong HUANG ; Yating HU ; Jing LI ; Yanbing YAO ; Xin-Jie YANG ; Jianhua WEI
Journal of Practical Stomatology 2024;40(2):233-240
Objective:To investigate the impact of BMI1 expression in OSCC on the recruitment and differentiation of tumor-associat-ed macrophages(TAMs).Methods:BMI1 expression in 519 cases of OSCC tissues and 44 normal controls was analyzed using online datasets of GEPIA 2.0,and validated in 3 cases of OSCC samples and controls by qRT-PCR and western blotting.The function of BMI1/NF-κB axis during OSCC carcinogenesis was investigated by CCK8 assays,wound healing test and transwell assays.Macrophage phenotypes and recruitment were determined using qRT-PCR and western blotting following coculture of the cells with human monocyte cells(THP-1)by OSCC conditioned medium.Moreover,a cell line-derived xenograft(CDX)model was used to detect the effect of BMI1 on tumor growth in vivo.Results:Compared with the normal tissues and cells,the expression level of BMI1 in OSCC tissues and cells was significantly upregulated.BMI1 knockdown impaired the proliferation,migration,and invasion abilities of OSCC cell lines in NF-κB-dependent manner.Furthermore,OSCC cells with high BMI1 expression inhibited the migration of THP-1 cells,promoted M2-like macrophage polarization through NF-κB pathway in vitro.Xenograft experiments further confirmed the inhibitory effect of BMI1 knockdown on the tumorigenesis ability of OSCC cells in vivo.Conclusion:BMI1 promotes M2-like polarization by regulating NF-κB and may be used as a potential therapeutic target for antitumor immunity.
5.Study on Performance Evaluation System of the Physician based on the Management by Objectives and Developmental Performance Appraisal
Peiqin NIU ; Longjun HU ; Lengchen HOU ; Jianhua HUANG ; Yingchuan LI ; Keqiang ZUO
Chinese Hospital Management 2024;44(7):63-66
Based on the management by objectives and developmental performance appraisal,Shanghai Tenth People's Hospital explored the performance appraisal scheme for attending,including disease-specific complexity,disease-specific difficulty,clinical risk-taking and comprehensive quality.Assessment and feedback work was imple-mented by the medical management department,which format a set of independent budget of the physician perfor-mance assessment system.It introduced incentive measures to encourage attending to treat difficult and critical cases,provided high quality medical services,and eventually enhance hospital management effectiveness to attending.
6.Mechanism prediction and verification of Cistanche deserticola in the treatment of inflammatory bowel disease
Ming QIAO ; Yi ZHU ; Junping HU ; Jianhua YANG
China Pharmacy 2024;35(21):2582-2589
OBJECTIVE To investigate the mechanism of Cistanche deserticola in the treatment of inflammatory bowel disease (IBD). METHODS The active components of C. deserticola were screened based on TCMSP and literature reports. The targets of active ingredients were obtained via Swiss Target Prediction platform. Then the disease targets were obtained by searching GeneCards and OMIM databases. PPI network and “drug-compound-disease-target” network were constructed. The core components and core targets were screened. GO and KEGG enrichment analyses were performed, and molecular docking verification was conducted for core targets and core components. The IBD mice model was established and divided into model group, positive control group (dexamethasone, 0.4 mg/kg) and C. deserticola extract group (100, 200, 400 mg/kg); blank control group was set, with 8 mice in each group. Each group was given relevant medicine, once a day, for 7 consecutive days. Disease activity index (DAI) score and colon length were calculated, and the pathological morphology of the colon of mice was observed. The levels of inflammatory factors [interleukin-6 (IL-6), IL-1β, IL-10, myeloperoxidase (MPO),tumor necrosis factor-α (TNF-α)] in colon tissue, and protein expressions of core targets were detected. RESULTS A total of 39 active ingredients and 232 potential targets of C. deserticola in the treatment of IBD were obtained. The treatment of IBD with C. deserticola might be related to core components such as quercetin, suchilactone, β-sitosterol and cistanoside H, and core targets such as TNF, AKT1, STAT3, EGFR and SRC. GO and KEGG pathway analysis predicted that the biological processes of C. deserticola in the treatment of IBD were mainly related to protein phosphorylation, and negative regulation of apoptosis, mainly involving PI3K/AKT and EGFR tyrosine kinase inhibitor resistance signaling pathways. The results of molecular docking showed that the binding energy between the core components and core target of C. deserticola was less than -4.7 kJ/mol. Animal experiment results showed that after intervention with C. deserticola extract, the body weight and colon length of mice significantly increased (P<0.05 or P<0.01), while DAI decreased significantly (P<0.05 or P<0.01). The congestion and edema of colon mucosa were significantly reduced, and the pathological score of colon tissue was significantly decreased (P<0.05 or P<0.01); the levels of IL-6, IL-1β, MPO and TNF-α, as well as the protein expressions of PI3K, phosphorylated PI3K (p-PI3K), EGFR, TNF- α, STAT3, phosphorylated STAT3 (p-STAT3), AKT1, phosphorylated AKT1 (p-AKT1) and SRC in colon tissue were reduced significantly (P<0.05 or P<0.01), while the level of IL-10 was significantly increased in model group (P<0.01). CONCLUSIONS C. deserticola may alleviate IBD by regulating the SRC/EGFR/PI3K/AKT signaling pathway.
7.Second-hand smoke behavior at home among smokers
CUI Ziyi ; WU Jiaqian ; HU Shiyao ; TANG Yan ; SHI Jianhua
Journal of Preventive Medicine 2024;36(11):1003-1007
Objective:
To investigate the second-hand smoke behavior at home among smokers, so as to provide the reference for developing home tobacco control strategies.
Methods:
Permanent residents who were smokers and at the ages of 15 years and above were sampled from 10 streets (townships) in Xuhui District, Shanghai Municipality using the multi-stage random sampling and population-size proportional sampling methods in 2022. Demographic information, smoking status, awareness of second-hand smoke hazards and second-hand smoke behavior at home were collected by questionnaire surveys. Factors affecting second-hand smoke behavior at home were identified using a multivariable logistic regression model.
Results:
A total of 1 024 smokers were surveyed, including 769 males (75.10%) and 255 females (24.90%). The awareness of hazards of second-hand smoke was 33.59%; the awareness rate of second-hand smoke causing lung cancer in adults was the highest at 76.76%, while the awareness rate of second-hand smoke leading to premature birth and low birth weight in newborns was the lowest at 39.45%. There were 459 smokers with second-hand smoke behavior at home, accounting for 44.82%. Multivariable logistic regression analysis showed that occupation (the retired, OR=2.320, 95%CI: 1.276-4.218), frequency of smoking (often, OR=5.722, 95%CI: 3.977-8.231), smoking duration (a year and above, OR=10.089, 95%CI: 5.508-18.480), electronic cigarette use (occasionally, OR=2.994, 95%CI: 1.283-6.986), living with pregnant women or infants (no, OR=2.171, 95%CI: 1.367-3.448), family indoor smoking restrictions (no restriction, OR=13.926, 95%CI: 7.538-25.727) and awareness of second-hand smoke hazards (unknown, OR=1.562, 95%CI: 1.067-2.287) were the influencing factors for second-hand smoke behavior at home.
Conclusion
There were 44.82% smokers in Xuhui District with second-hand smoke behavior at home, which was influenced by occupation, living situation, smoking status, family indoor smoking restriction and awareness of second-hand smoke hazards.
8.Exploring the Mechanism of Cichorium Glandulosum in the Treatment of Liver Fibrosis Based on Network Pharmacology and Experimental Validation
Jianhua YANG ; Ruoyu GENG ; Wei ZANG ; Qian LI ; Chao DU ; Junping HU
Chinese Journal of Modern Applied Pharmacy 2024;41(3):303-312
OBJECTIVE
To investigate the mechanism of Cichorium glandulosum in the treatment of liver fibrosis by using network pharmacology and experimental validation.
METHODS
A "component-target-pathway" network was constructed with the help of TCMSP, Pubchem, SwissTargetPrediction and Genecards databases, and the STRING database was used to predict the targets of Cichorium glandulosum against liver fibrosis. KEGG and GO enrichment analysis was performed in the DAVID database, and molecular docking of active ingredients and key targets was docked in AUTODOCK. PDGF-BB was used to induce activation of cells and verify the effects of six compounds, including quercetin, quercetin, chicoric acid, caffeic acid, chlorogenic acid, and isochlorogenic acid, on the proliferation, apoptosis, and liver fibrosis indicators of HSC-T6 cells. Western blotting was used to detect the expression of Ras, ERK1, ERK2, C-fos, and JNK proteins in HSC-T6 cells.
RESULTS
Network pharmacology screened 239 common targets between the components and liver fibrosis, PPI analysis showed that SRC, STAT3, HSP90AA1 and other targets were key targets, KEGG analysis showed that the pathways affected by Cichorium glandulosum included cancer pathways, metabolic pathways, etc. GO analysis predicted that Cichorium glandulosum mainly affected processes such as signal transduction. The molecular docking results showed that the target that could bind well with the components MAPK1, and the components that could bind well with the target aesculetin, caffeic acid and chlorogenic acid. Compared with the model group, the inhibition effect of the six compounds on PDGF-BB-induced HSC-T6 cell activation was stronger, and all 6 compounds had the effects to reverse the index of liver fibrosis, in which aesculetin had the strongest activity(P<0.01). The expression of Ras, ERK1, ERK2, C-fos, and JNK in HSC-T6 cells decreased after the interventions of 6 compounds.
CONCLUSION
Each component of Cichorium glandulosum has different anti liver fibrosis effects, which are related to the inhibition of ERK/RAS pathway activation.
9.Effective Components and Mechanism of Cistanches Herba Aqueous Extract Against Diabetic Nephropathy Based on the Spectral-effect Relationship
Tianhua LIU ; Chong MA ; Baicai WANG ; Ruoyu GENG ; Yao ZHAO ; Junping HU ; Jianhua YANG
Chinese Journal of Modern Applied Pharmacy 2024;41(10):1313-1323
OBJECTIVE
To screen out the pharmacodynamic substances of Cistanches Herba aqueous extracts, explore the basis of the pharmacodynamic substances and their mechanism of action in the treatment of diabetic nephropathy(DN), based on the spectral relationship between the mass spectral peak areas of different elution sites of Cistanches Herba aqueous extracts and their anti-DN effects.
METHODS
UPLC-Orbitrap-MS/MS technique was used to characterise the chromatographic peaks; MTT method was used to detect the effects of different elution sites of Cistanches Herba aqueous extract on the proliferation of high glucose and high fat HK-2 cells; grey correlation analysis and partial least squares method were used to analyse the spectral relationship between mass spectrometry peak area and anti-DN activity. MTT method was used to determine the anti-DN activities of the individual components of Cistanches Herba aqueous extract; biochemical kit and ELISA were used to determine the levels of oxidative indicators(SOD, GSH-P) and inflammatory factors(IL-1β, TNF-α, TGF-β); Western blotting was used to detect the expression of apoptosis-related proteins.
RESULTS
UPLC-Orbitrap-MS/MS technique speculated and identified 72 common compounds; In Cistanches Herba aqueous extracts, water, 20% ethanol, and 40% ethanol-eluted sites differentially increased the proliferation rate of HK-2 cells in a high-sugar, high-fat environment; Partial least squares and grey correlation analyses showed that the constituents of the aqueous extracts of Cistanches Herba with greater anti-DN contributions were 8-epideoxymatricinic acid, geniposidic acid, pinoresinol, betaine and syringin, et al. MTT assay reveals that 8-epi-deoxystrychnic acid and geniposidic acid had significant proliferative effects on HK-2 cells in a high glucose and high fat environment; Biochemical kit and ELISA showed that 8-epideoxystrychnic acid and geniposidic acid were able to up-regulate the activity of SOD and GSH-Px, and at the same time they had an inhibitory effect on the expression of inflammatory factors IL-1β, TNF-α and TGF-β. Western blotting results showed that 8-epideoxystrychnic acid and geniposidic acid were able to down-regulate and up-regulate the markers of dermal mesenchymal transition: α-SMA, Collagen Ⅰ and E-cadherin, and they could exert anti-DN effects by inhibiting the PI3K-Akt pathway.
CONCLUSION
The two compounds, 8-epideoxystrychnic acid and geniposidic acid, which are screened by the spectroeffective relationship of anti-DN among the many chemical constituents contained in Cistanches Herba, can affect oxidative stress, inflammation and epithelial-mesenchymal transformation of renal tubular cells by inhibiting the PI3K-Akt signalling pathway, and improve renal pathology, degree of fibrosis and renal function, which will be useful for the in-depth study of aqueous extracts of Cistanches Herba in the treatment of DN.
10.Advances in oxidative stress-related pathways with diagnostic and predictive value in schizophrenia
Tianyue YU ; Qian GUO ; Hao HU ; Yujing SU ; Jianhua CHEN
The Journal of Practical Medicine 2024;40(20):2935-2940
Schizophrenia is a severe mental illness with a significant disease burden.The interaction between oxidative stress and pro-inflammatory factors promotes chronic neuroinflammation and immune damage,leads to dysregulation of dopaminergic and glutamatergic pathways and occurrence of psychotic symptoms and is believed to be closely related to the pathogenesis of schizophrenia.In this paper,we aim to identify biomarkers within the tryptophan kynurenine metabolic pathway,the WNT/β-Catenin pathway and the NF-κB pathway,and dopamine metabolism.These pathways have been extensively studied and are known to be involved in the interac-tion between inflammation and oxidative stress.We will also explore the potential application of related antioxidants in the diagnosis and treatment of schizophrenia,summarizing their current research progress.


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