1.Study on the effects of carvacrol on stomach-heat and stomach-cold rats and its mechanism of cooling and clearing based on energy metabolism and gastrointestinal function
Qi ZHANG ; Yi LI ; Hongye LI ; Fengwei ZHANG ; Minghui JIANG ; Xingyu ZHAO ; Linze LI ; Xiaofang WU ; Yinming ZHAO ; Songrui DI ; Jianjun ZHANG ; Chun WANG ; Linyuan WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):471-482
Objective:
To investigate the biological effects of carvacrol on rats with stomach-heat and stomach-cold and its regulation on transient receptor potential(TRP) channels in rats with stomach-heat, and to study the cold and heat properties of carvacrol and its possible mechanism.
Methods:
According to the random number method, 100 SD rats were divided into stomach-heat blank group, stomach-heat model group, Coptidis Rhizoma group, stomach-heat low-dose and high-dose carvacrol group, stomach-cold blank group, stomach-cold model group, Baked ginger group, stomach-cold low-dose group and high-dose carvacrol group, 10 rats in each group. The rat model of stomach-heat was established by intragastric administration of pepper aqueous solution (0.80 g/kg) and anhydrous ethanol, and the rat model of stomach-cold was established by intragastric administration of water extract of Anemarrhena asphodeloides and sodium hydroxide (10.40 g/kg). On the day of modeling, the rats in the Baked ginger group were given Baked ginger decoction (0.78 g/kg), and the rats in the Coptidis Rhizoma group were given Coptidis Rhizoma decoction (0.43 g/kg).The stomach-cold and stomach-heat low-dose group of carvacrol was given carvacrol emulsion (40 mg/kg), high-dose group was given carvacrol emulsion (80 mg/kg).All rats of the blank and model groups were given the equal volume of emulsion prepared by 5% dimethyl sulfoxide, 1% Tween 80, 1% polyethylene glycol 400, and 93% normal saline, once a day, for 7 days. The general condition of rats was observed and the body mass was recorded. The pathological morphology of gastric tissue was observed by hematoxylin-eosin staining. The changes of material and energy metabolism, cyclic nucleotide (cAMP), thyroid hormone and gastrointestinal hormone in each group were determined by enzyme-linked immunosorbent assay. The expression levels of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential channel M8 (TRPM8) and uncoupling protein-1 (UCP1) in rats with gastric fever were detected by Western blotting.
Results:
Compared with the stomach-heat blank group, the body mass of rats in the stomach-heat model group decreased at the fifth and seventh day (P<0.05). The contents (or ratio) of hepatic glycogen (HGlyc), total cholesterol (TC), triglyceride (TG), and vasoactive intestinal peptide (VIP) were decreased (P<0.05), and Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cytochrome C oxidase (COX), NADH dehydrogenase (ND), cyclic adenosine phosphate (cAMP), cAMP/cyclic guanosine phosphate (cGMP), triiodothyronine (T3), thyroxine (T4), gastrin (GAS), motilin (MTL), and α-amylase (α-AMS) all increased (P<0.05). Compared with the stomach-heat model group, the body mass of rats in the Coptidis Rhizoma group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, VIP and α-AMS were increased, and Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and GAS all decreased (P<0.05). The body mass of rats in the stomach-heat low-dose carvacrol group decreased at the seventh day. The contents (or ratio) of HGlyc, TC, and VIP were increased, Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and MTL all decreased, the expression of TRPV1 and UCP1 in gastric tissue decreased, while TRPM8 increased (P<0.05) in rats of the stomach-heat low-dose and high-dose carvacrol groups. Compared with the stomach-cold blank group, the body mass of rats in the stomach-cold model group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, α-AMS, and VIP all increased, while Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, GAS, and MTL all decreased (P<0.05). Compared with the stomach-cold model group, the body mass of rats in the Baked ginger group was increased at the seventh day, and the contents (or ratio) of HGlyc, VIP, and α-AMS all decreased, while Na+ -K+ -ATPase, COX, ND, cAMP/cGMP, T3, T4, GAS, and MTL all increased (P<0.05). The contents of HGlyc, cAMP, α-AMS, and VIP of rats in the stomach-cold low and high-dose carvacrol group all decreased (P<0.05). TG in the stomach-cold low-dose carvacrol group was increased. TC, Ca2+ -Mg2+ -ATPase, and cGMP all increased, while cAMP/cGMP decreased (P<0.05) in the high-dose carvacrol group.
Conclusion
In this study, the rat model of stomach-cold and stomach-heat were successfully established by using cold and heat factors. The result showed that carvacrol had a certain inhibitory effect on body mass, material energy metabolism, cyclic nucleotide level, thyroid hormone and gastrointestinal function in rats with stomach-heat, indicating that the drug was cold. Carvacrol′s cold medicinal property could be biologically explained by TRPV1 activation, UCP1 induction, and TRPM8 suppression.
2.C/EBPβ-Lin28a positive feedback loop triggered by C/EBPβ hypomethylation enhances the proliferation and migration of vascular smooth muscle cells in restenosis.
Xiaojun ZHOU ; Shan JIANG ; Siyi GUO ; Shuai YAO ; Qiqi SHENG ; Qian ZHANG ; Jianjun DONG ; Lin LIAO
Chinese Medical Journal 2025;138(4):419-429
BACKGROUND:
The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis.
METHODS:
Restenosis and atherosclerosis rat models of type 2 diabetes ( n = 20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student's t -test and one-way analysis of variance were used for statistical analysis.
RESULTS:
C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitroC/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells.
CONCLUSION
Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis.
Animals
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Cell Proliferation/genetics*
;
Cell Movement/genetics*
;
Muscle, Smooth, Vascular/metabolism*
;
Rats
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DNA Methylation/physiology*
;
CCAAT-Enhancer-Binding Protein-beta/genetics*
;
Male
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Myocytes, Smooth Muscle/cytology*
;
Rats, Sprague-Dawley
;
RNA-Binding Proteins/genetics*
;
Cells, Cultured
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Coronary Restenosis/metabolism*
3.Diagnosis and treatment of colorectal liver metastases: Chinese expert consensus-based multidisciplinary team (2024 edition).
Wen ZHANG ; Xinyu BI ; Yongkun SUN ; Yuan TANG ; Haizhen LU ; Jun JIANG ; Haitao ZHOU ; Yue HAN ; Min YANG ; Xiao CHEN ; Zhen HUANG ; Weihua LI ; Zhiyu LI ; Yufei LU ; Kun WANG ; Xiaobo YANG ; Jianguo ZHOU ; Wenyu ZHANG ; Muxing LI ; Yefan ZHANG ; Jianjun ZHAO ; Aiping ZHOU ; Jianqiang CAI
Chinese Medical Journal 2025;138(15):1765-1768
4.Successful in situ 5-aminolevulinic acid photodynamic therapy in a 53-year-old female with cutaneous squamous cell carcinoma.
Limin LUO ; Xiaoling JIANG ; Jianjun QIAO ; Hong FANG ; Jun LI
Journal of Zhejiang University. Science. B 2025;26(9):915-922
Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), as certain forms of non-melanoma skin cancer (NMSC) or keratinocyte carcinoma, are the most common forms of malignant neoplasms worldwide (Sharp et al., 2024). BCC and cSCC have been identified as two major components of NMSC, comprising one-third of all malignancies (Burton et al., 2016). Generally speaking, patients with NMSC tend to have relatively favorable survival outcomes, while different histopathological subtypes of NMSC exhibit distinct biological behaviors (Stătescu et al., 2023). Keratinocyte carcinoma, although not considered as deadly as melanoma, tends to metastasize if left untreated (Civantos et al., 2023; Nanz et al., 2024). cSCC can evolve locally, then aggressively metastasize, invade, and even lead to fatal consequences in a subset of patients (Winge et al., 2023). A solid, pigmented, smooth plaque or a hyperkeratotic papule with or without central ulceration and hemorrhage appears to be characteristic of cSCC (Thompson et al., 2016; Zhou et al., 2023). Of note, a rare type of intraepidermal cSCC in situ often appears as a velvety, demarcated, slightly raised erythematous plaque on the genitalia of men (Yamaguchi et al., 2016). Accounting for approximately 16.0% of scalp tumors and with a rising incidence, cSCC is now the second most common NMSC in humans (Verdaguer-Faja et al., 2024). According to the latest statistics, up to 2%‒5% of cSCCs in situ may gradually progress into invasive cSCCs in the final step (Rentroia-Pacheco et al., 2023). Several risk factors for the carcinogenesis and development of cSCC have been identified, including age, accumulative exposure to ultraviolet light radiation A and B, human papillomavirus infection, arsenic ingestion, chronic scarring, xeroderma pigmentosa, a relevant history of ionizing radiation, androgenetic alopecia in males, and immunosuppression therapy (Martinez and Otley, 2001; Welsch et al., 2012; Mortaja and Demehri, 2023).
Humans
;
Aminolevulinic Acid/therapeutic use*
;
Skin Neoplasms/pathology*
;
Photochemotherapy/methods*
;
Female
;
Carcinoma, Squamous Cell/pathology*
;
Middle Aged
;
Photosensitizing Agents/therapeutic use*
;
Carcinoma, Basal Cell/drug therapy*
5.Clinical characteristics and genetic analysis of a family with neurodevelopmental syndrome caused by the SPTBN1 gene mutation
Huimin ZHAO ; Jianjun TANG ; Linze JIANG ; Kaili SHI
Chinese Journal of Applied Clinical Pediatrics 2024;39(11):866-868
The clinical and genetic characteristics of the family reported with neurodevelopmental syndrome caused by the SPTBN1 gene mutation were analyzed for clinical diagnosis.The proband was a boy, 2 years and 3 months old, admitted to the Department of Neurology, Guangzhou Women and Children′s Medical Center in June 2022 with comprehensive developmental delays as the main manifestation.The boy was backward in development since childhood.He was able to raise his head at the age of 3 months and sit alone at the age of 11 months.He could stand up with support but was unable to climb.He occasionally spoke polysyllabic words.The proband′s elder brother, 3 years and 1 month old, was able to walk at the age of 1 year and 6 months, and could speak " Mom and Dad" consciously and understand some instructions.He liked to play with other children.The mother of the proband was mentally retarded, while the father and grandparents of the proband had no symptoms.The proband was found to have a heterozygous mutation of the SPTBN1 gene (NM_003128.3), c.811G>A (p.Val271Met).The proband′s mother and elder brother also had a heterozygous mutation, which, however, was not detected in the proband′s father.The neurodevelopmental syndrome caused by the SPTBN1 gene mutation is rare in China, which can be manifested as language and motor delays and intellectual disabilities from early childhood, and individuals with the same genetic variation show different clinical phenotypes.
6.Esketamine Improves Working Memory Impairment in Neuropathic Mice Through Hippocampal BDNF-TrkB Pathway
Yubin JIANG ; Xingming WANG ; Yue ZHANG ; Zhiqiang ZHOU ; Jianjun YANG
Medical Journal of Peking Union Medical College Hospital 2024;15(2):328-334
7.Expression and pathological diagnostic value of extracellular matrix metalloproteinase inducer,ma-trix metalloproteinase-9 and lysine demethylase 6B in invasive breast cancer
Huang JIANG ; Lihua ZHENG ; Xiaoyan XU ; Jianjun WANG ; Xianwei XU ; Na WANG ; Chenju XING ; Xianyu LU
Journal of Xinxiang Medical College 2024;41(2):143-150
Objective To investigate the expressions of extracellular matrix metalloproteinase inducer(EMMPRIN),matrix metalloproteinase-9(MMP-9),lysine demethylase 6B(KDM6B)proteins and their correlation with clinicopathologic features in invasive breast cancer,and analyze the correlation among the three proteins and their value in pathological diagnosis of invasive breast cancer.Methods The surgical biopsy specimens of 124 patients with invasive breast cancer who were admitted to the Department of Pathology,the Fifth Clinical Medical College of Henan University of Chinese Medicine/People's Hospital of Zhengzhou from January 2014 to December 2017 were selected as research subjects,and 20 low-grade intraductal carcinoma tissue specimens,27 high-grade intraductal carcinoma tissue specimens,and 22 adjacent tissue specimens>1 cm away from the invasive breast cancer were selected as controls.The expressions of EMMPRIN,MMP-9 and KDM6B proteins in cancer-adjacent tissues,low-grade intraductal carcinoma tissues,high-grade intraductal carcinoma tissues and invasive breast cancer tissues were detected by immunohistochemistry.The relationship between the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins and clinicopathologic features of invasive breast cancer was analyzed,Spearman correlation analysis was used to evaluate the correlation of EMMPRIN,MMP-9 and KDM6B proteins in breast cancer tissues,and receiver operating characteristic(ROC)curve was adopted to evaluate the diagnostic value of EMMPRIN,MMP-9 and KDM6B for invasive breast cancer.Results The relative expressions of EMMPRIN and MMP-9 proteins in high-grade intraductal carcinoma and invasive breast cancer tissues were significantly higher those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P<0.05);the relative expressions of EMMPRIN and MMP-9 proteins in invasive breast cancer tissues were significantly higher those in high-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than that in high-grade intraductal carcinoma tissues(P<0.05);there was no statistically significant difference in the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins between cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P>0.05).The relative expressions of EMMPRIN and KDM6B proteins were not related to the age,tumor location and tumor diameter of patients with invasive breast cancer(P>0.05),and the relative expression of MMP-9 protein was not related to the age and tumor location of patients with invasive breast cancer(P>0.05).Relative expressions of EMMPRIN,MMP-9 and KDM6B proteins were correlated with WHO grading,lymph node metastasis,and tumor,node and metastasis(TNM)staging of invasive breast cancer(P<0.05),and the relative expression of MMP-9 protein was correlated with the tumor diameter(P<0.05).In the WHO grades Ⅰ,Ⅱ,and Ⅲ of invasive breast cancer,the relative expressions of EMMPRIN and MMP-9 proteins increased sequentially,while the relative expression of KDM6B protein decreased sequentially(P<0.05);the relative expressions of EMMPRIN and MMP-9 proteins in the lymph node metastasis group were significantly higher than those in the non-lymph node metastasis group,and the relative expression of KDM6B protein was significantly lower than that in the non-lymph node metastasis group(P<0.05);the relative expressions of EMMPRIN and MMP-9 proteins in TNM stages Ⅲ-Ⅳ were significantly higher than those in stages Ⅰ-Ⅱ(P<0.05),while the relative expression of KDM6B protein was significantly lower than that in stages Ⅰ-Ⅱ(P<0.05).In the group of invasive breast cancer with diameter≤2 cm,2 to 5 cm,and>5 cm,the relative expression of MMP-9 protein increased sequentially(P<0.05).Spearman correlation analysis showed that the expression of EMMPRIN was positively correlated with MMP-9 protein in invasive breast cancer tissues(r=0.990,P=0.000),the expression of EMMPRIN was negatively correlated with KDM6B protein(r=-0.606,P=0.000),and the expression of MMP-9 was negatively correlated with KDM6B protein(r=-0.612,P=0.000).ROC curve analysis showed that the area under the curve(AUC)of EMMPRIN protein for diagnosing invasive breast cancer was 0.875[95%confidence interval(CI):0.823-0.926,P<0.05],with an optimal threshold of 10.043,sensitivity of 79.0%,and specificity of 76.8%;the AUC of MMP-9 protein in diagnosing invasive breast cancer was 0.863(95%CI:0.808-0.917,P<0.05),with an optimal threshold of 10.070,sensitivity of 74.2%,and specificity of 76.8%;the AUC of KDM6B protein in diagnosing invasive breast cancer was 0.267(95%CI:0.196-0.338,P<0.05),with an optimal threshold of 11.003,sensitivity of 71.0%,and specificity of 98.6%.Conclusion EMMPRIN,MMP-9 and KDM6B are related to the occurrence and development of invasive breast cancer.Detection of the expressions of EMMPRIN,MMP-9 and KDM6B is helpful to the pathological diagnosis of invasive breast cancer and clinical judgment of invasion and metastasis of breast cancer.
8.A Lean Operation Management Model for Public Hospital is Constructed Based on Evidence Based Deci-sion-Making
Yaojun ZHAO ; Leichao WANG ; Jianjun LI ; Shua JIANG ; Li ZHENG ; Wenwen LIU ; Zihan MU ; Zhiping GUO
Chinese Hospital Management 2024;44(3):5-8
Comprehensively improving the new efficiency of high-quality development of public hospitals is the key top-level design for deepening the reform of public hospitals during the"14th Five-Year Plan"period.In view of the changes in the macro environment faced by public hospitals in recent years,such as the cancellation of the addi-tion of pharmaceutical consumables and the deep promotion of the reform of payment methods,as well as the out-standing problems existing at the micro level of public hospital operation,such as the separation of diagnosis and treatment business from economic operation activities,extensive decision-making methods,unreasonable alloca-tion of resources and urgent optimization of processes.By referring to relevant theories such as value management theory,a new"trinity"public hospital lean operation management model based on"integration of industry and fi-nance,lean operation and evidence-based decision-making"is explored and constructed.It breaks the relatively parallel operation barriers of clinical diagnosis and treatment business and economic operation management,innovates a new method of linear staff management with the integration of industry and finance,gives full play to the role of experts in governing hospitals,and integrates the professional committee system driven by"technology+manage-men"into the hospital decision-making staff system to provide data evidence-based basis for assisting the hospital leadership to make scientific decisions.
9.Research on the Economic Operating Mechanisms of Large Public Hospitals in Henan Province
Rui JIANG ; Jianjun LI ; Jian WU ; Wei NIU ; Li ZHENG ; Chenqi LI ; Yanyu TANG ; Yaojun ZHAO
Chinese Hospital Management 2024;44(3):17-20
The establishment of an economic operating mechanisms for hospitals is a key factor in advancing the growth of public hospitals in the modern age.At present,the due value of key factors such as medical resources and labor value of medical personnel in public hospitals in China has not been fully reflected,which not only restricts the overall operation efficiency of hospitals,but also makes it difficult to realize the marginal value of hospital operation and management.The economic operating mechanisms of public hospitals is in urgent need of reform.Large public hospitals in Henan Province has established an economic operating mechanisms of public hospitals based on intelli-gent finance,comprehensive budget management as the core,and cost control and performance management as the major tools to realize the interconnection of various systems and promote the high-quality development of hospi-tals with the three major supports of industry and finance integration,financial integration and financial integration.
10.Immune reconstitution and influencing factors in HIV infected men who have sex with men with access to antiviral therapy in Guangxi Zhuang Autonomous Region from 2005 to 2021
Ni CHEN ; He JIANG ; Huanhuan CHEN ; Qiuying ZHU ; Xiuling WU ; Jianjun LI ; Nengxiu LIANG ; Qin MENG ; Xuanhua LIU ; Jinghua HUANG ; Wenxuan HOU ; Zhaoquan WANG ; Guanghua LAN
Chinese Journal of Epidemiology 2024;45(4):529-535
Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.


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