1.Prevention and Treatment of Cardiovascular-Kidney-Metabolic Syndrome with Traditional Chinese Medicine Based on the Core Pathogenesis Evolution of "Constraint,Heat,Deficiency,Stasis,and Toxin"
Zhichao RUAN ; Jiangteng LIU ; Hua ZHANG ; Weijun HUANG ; Qiang FU ; Shidong WANG ; Jinxi ZHAO
Journal of Traditional Chinese Medicine 2025;66(7):680-684
Traditional Chinese medicine (TCM) offers a rich theoretical foundation and clinical experience for the prevention and treatment of cardiovascular-kidney-metabolic syndrome(CKM), demonstrating unique advantage. Building on previous work in managing diabetes, its complications, and chronic kidney disease, our team has proposed a five-phase evolution theory of "constraint, heat, deficiency, stasis, and toxin" as the core pathogenesis. These phases correspond to the pathological progression of constraint of phlegm-dampness, constraint transforming into heat, heat damaging qi and yin, stasis accumulated in the collateral vessels, and toxin induced by deficiency and stasis. In the prevention and treatment of CKM by TCM, it is emphasized to integrate the concept of "treating disease before it arises" with constitution theory, and incorporate the "2-5-8" prevention and treatment strategy, which combines prevention with treatment, tailors interventions to different phases, and employs comprehensive treatment modalities. Our goal is to leverage TCM's holistic advantages in preventing and treating CKM.
2.Adjuvant strategies for patients with T1b invasion after endoscopic submucosal dissection for esophageal squamous cell carcinoma
Kaiyuan ZHU ; Yuchen SU ; Zhichao LIU ; Hong ZHANG ; Chunguang LI ; Jie ZHANG ; Zhigang LI
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(1):116-123
Objective·To compare the prognostic effects of radical resection of esophageal cancer,concurrent chemoradiotherapy and simple follow-up observation on the prognosis of patients with T1b invasion of superficial esophageal squamous cell carcinoma after endoscopic submucosal dissection(ESD).Methods·From May 2016 to May 2021,the clinical data of 67 patients with esophageal squamous cell carcinoma who were pathologically confirmed as pT1b after ESD and treated in Shanghai Chest Hospital were retrospectively analyzed.According to the additional treatment after ESD,the patients were divided into additional surgery group(S group),chemoradio-therapy group(CRT group)and observation group(O group).χ2 test was used to compare the clinical baseline data and pathological information of the three groups of patients.The Kaplan-Meier survival curve and log-rank test were used to compare the disease free survival(DFS)and recurrence free survival(RFS)of the three groups of patients,and the Cox proportional hazards regression model was used on DFS and RFS by univariate and multivariate analysis.Results·Among all 67 patients,there were 23 cases in the S group,19 cases in the CRT group,and 25 cases in the O group.There was no significant difference in age(P=0.080),gender(P=0.078),tumor length(P=0.485),tumor location(P=0.655),lesion circumferential ratio(P= 0.310),histological grading(P=0.084),depth of tumor invasion(P=0.066)and lymphovascular invasion(P=0.279)among the three groups.During(42.6±16.7)months of follow-up,tumor recurrence was observed in 10 cases(14.9%),including 6 patients(60%)with local recurrence,2 patients(20%)with regional lymph recurrence and 2 patients(20%)with distant metastasis.The median recurrence time of group S,group CRT,and group O was 40.1,36.6,and 22.1 months,and the 3-year DFSs were 100%,89.5%,and 74.5%(P-trend=0.040).Multivariate Cox analysis showed that additional esophagectomy was the key to improving independent protective factors of RFS(HR=0.097,95%CI 0.010?0.956,P=0.046).Conclusion·For patients with superficial esophageal squamous cell carcinoma confirmed as pT1b after ESD,additional surgery can significantly reduce the possibility of long-term recurrence.
3.Preparation and characterization of methacryloylated hyaluronic acid/acellular Wharton's jelly composite hydrogel scaffold
Xun YUAN ; Zhengang DING ; Liwei FU ; Jiang WU ; Yazhe ZHENG ; Zhichao ZHANG ; Guangzhao TIAN ; Xiang SUI ; Shuyun LIU ; Quanyi GUO
Chinese Journal of Tissue Engineering Research 2024;28(22):3517-3523
BACKGROUND:As tissue engineering brings new hope to the worldwide problem of articular cartilage repair,the construction of light-curing 3D printed hydrogel scaffolds with biomimetic composition is of great significance for cartilage tissue engineering. OBJECTIVE:To construct a biomimetic methacryloylated hyaluronic acid/acellular Wharton's jelly composite hydrogel scaffold by digital light processing 3D printing technology,and to evaluate its biocompatibility. METHODS:Wharton's jelly was isolated and extracted from human umbilical cord,then decellulated,freeze-dried,ground into powder,and dissolved in PBS to prepare 50 g/L acellular Wharton's jelly solution.Methylallylated hyaluronic acid was prepared,lyophilized and dissolved in PBS to prepare 50 g/L methylallylated hyaluronic acid solution.Acellular Wharton's jelly solution was mixed with methacrylyacylated hyaluronic acid solution at a volume ratio of 1:1,and was used as bio-ink after adding photoinitiator.Methylacrylylated hyaluronic acid hydrogel scaffolds(labeled as HAMA hydrogel scaffolds)and methylacrylylated hyaluronic acid/acellular Wharton's jelly gel scaffolds(labeled as HAMA/WJ hydrogel scaffolds)were prepared by digital light processing 3D printing technology,and the microstructure,swelling performance,biocompatibility,and cartilage differentiation performance of the scaffolds were characterized. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the two groups of scaffolds showed a three-dimensional network structure,and the fiber connection of HAMA/WJ hydrogel scaffold was more uniform.Both groups achieved swelling equilibrium within 10 hours,and the equilibrium swelling ratio of HAMA/WJ hydrogel scaffold was lower than that of HAMA hydrogel scaffold(P<0.05).(2)CCK-8 assay showed that HAMA/WJ hydrogel scaffold could promote the proliferation of bone marrow mesenchymal stem cells compared with HAMA hydrogel scaffold.Dead/live staining showed that bone marrow mesenchymal stem cells grew well on the two groups of scaffolds,and the cells on the HAMA/WJ hydrogel scaffolds were evenly distributed and more cells were found.Phalloidine staining showed better adhesion and spread of bone marrow mesenchymal stem cells in HAMA/WJ hydrogel scaffold than in HAMA.(3)Bone marrow mesenchymal stem cells were inoculated into the two groups for chondrogenic induction culture.The results of qRT-PCR showed that the mRNA expressions of agglutinoglycan,SOX9 and type Ⅱ collagen in the HAMA/WJ hydrogel scaffold group were higher than those in the HAMA hydrogel scaffold group(P<0.05,P<0.01).(4)These findings indicate that the digital light processing 3D bioprinting HAMA/WJ hydrogel scaffold can promote the proliferation,adhesion,and chondrogenic differentiation of bone marrow mesenchymal stem cells.
4.Exploring the Mechanism of Action of Jintiange Capsules in Regulating SMSC-Exos miRNA and Articular Chondrocytes mRNA for the Treatment of Osteoarthritis in Rats Based on Transcriptome
Zhichao WANG ; Xue ZHANG ; Xiaofei ZHANG ; Yajun SHI ; Dongyan GUO ; Fei LUAN ; Bingtao ZHAI ; Junbo ZOU ; Puwei YUAN
Chinese Journal of Modern Applied Pharmacy 2024;41(11):1464-1475
OBJECTIVE
To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology.
METHODS
Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA.
RESULTS
Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA.
CONCLUSION
Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.
5.Discussion of Hp(3) calibration with two thermoluminescent dosimeters in the same standard X-ray RQR radiation field
Wenyan LI ; Guiying ZHANG ; Lantao LIU ; Dongsheng NIU ; Zeqin GUO ; Zhichao WANG ; Hua TUO ; Heyan WU ; Tingting XIA ; Nini CHU ; Jichuan LAI ; Jiaojiao CHEN
Chinese Journal of Radiological Health 2024;33(3):318-322
Objective To compare Hp(3) calibration with a homemade (A) thermoluminescent dosimeter (TLD) and an imported (B) TLD in a standard X-ray RQR radiation field, to explore the different responses of A and B, and to provide foundation for the calibration of Hp(3). Methods A column mode was selected. Hp(3) calibration was performed using A and B in a standard X-ray RQR radiation field in the Secondary Standard Dosimetry Laboratory, National Institute for Radiological Protection, China Center for Disease Control and Prevention. Angle response, energy response, and linear response were calibrated with RQR4 (60 kV), RQR7 (90 kV), and RQR9 (120 kV), respectively. Results In terms of angle response, the calibration results of A were relatively high, while the calibration results of B were relatively low. In terms of energy response, the calibration results showed a similar pattern to angle response. In terms of linear response, the calibration results of both A and B were satisfactory. Conclusion Both A and B can be used for normal calibration of Hp(3) in a standard X-ray RQR radiation field. However, in actual monitoring, attention should be paid to the energy and angle response values of TLDs.
6.Effect of high glucose on immune escape of pancreatic cancer cells by regulating miR-429/ZEB1 axis
Zhichao ZHANG ; Guanghui LI ; Xuehe ZHU ; Qiang WEI ; Fei WANG ; Haiping ZHAO
Acta Universitatis Medicinalis Anhui 2024;59(7):1166-1174
Objective To explore the impact of high glucose(HG)intervention on immune escape of pancreatic cancer cells and its molecular mechanisms.Methods PANC-1 cells were treated with different concentrations of glucose(0,7.5,15,30 mmol/L)for 24 h to establish high glucose intervention PANC-1 cells.miR-429 mimics and its negative control(mimics NC)were transfected into PANC-1 cells,which were divided into control group,HG group,HG+mimics NC group,HG+mimics group,HG+mimics+oe-NC group,and HG+mimics+oe-ZEB1 group.Flow cytometry was utilized to measure the expression level of cell surface molecule PD-L1;qRT-PCR was used to detect the expression levels of miR-429 and ZEB1 mRNA in cells;Western blot was used to detect the ex-pression level of ZEB1 protein in cells.The above-mentioned PANC-1 cells from each group were co-cultured with CD8+T cells to establish a co-culture system,and CCK-8 was used to assess cell proliferation activity;apoptosis levels of cells were measured using flow cytometry;lactate dehydrogenase(LDH)release assay was used to detect the killing effect of CD8+T cells on PANC-1 cells;dual-luciferase reporter system was used to validate the target-regulatory relationship between mi R-429 and ZEB1.Results HG could promote the expression of cell surface mole-cules PD-L1 and ZEB1 in PANC-1 cells(P<0.05),inhibit the expression of miR-429,and exhibit concentration dependence.Overexpression of miR-429 could significantly suppress the expression of cell surface molecule PD-L1 induced by HG in PANC-1 cells,while overexpression of ZEB1 could reverse the inhibitory effect of miR-429 over-expression on the expression of cell surface molecule PD-L1 induced by HG.After establishing a co-culture system with CD8+T cells,compared with the control group,the proliferation activity of PANC-1 cells in the HG group sig-nificantly increased,and the apoptosis rate and cytotoxicity significantly decreased(P<0.05).Compared with the HG+mimics NC group,the proliferation activity of PANC-1 cells in the HG+mimics group significantly decreased,and the apoptosis level and cytotoxicity significantly increased(P<0.05).Compared with the HG+mimics group,the proliferation activity of PANC-1 cells in the HG+mimics+oe-ZEB1 group significantly increased,and the apop-tosis rate and cytotoxicity significantly decreased(P<0.05).Dual luciferase reporter gene assay confirmed that miR-429 negatively regulated ZEB1.Conclusion High glucose promotes immune escape of PANC-1 cells by down-regulating the expression level of miR-429,negatively regulating the expression of ZEB1 mRNA,and increasing the expression level of cell surface molecule PD-L1 in PANC-1 cells.
7.Diagnostic value of H3.3G34W,p63 and SATB2 immunohistochemical staining combined in giant cell tumor of bone
Nan ZHANG ; Moqi LÜ ; Zhichao TONG ; Haiyan LI ; Dan WANG ; Wenyi YANG ; Xiaoju LI ; Dangxia ZHOU
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(3):461-469
Objective To investigate the expressions of H3.3G34W,p63 and SATB2 in giant cell tumor of bone(GCTB)and the effect and value of their combined application in the diagnosis of GCTB.Methods We collected the samples and medical records of 54 cases of GCTB and 83 cases of non-giant cell tumor of bone(14 cases of aneurysmal bone cyst,16 cases of chondroblastoma and 53 cases of non-ossifying fibroma)diagnosed between 2020 and 2022 in the Department of Pathology of Honghui Hospital Affiliated to Xi'an Jiaotong University.The expressions of H3.3G34W,p63 and SATB2 were detected by EliVision immunohistochemical method.X2 test was used to determine whether there are significant differences in the positive rates of H3.3G34W,p63 and SATB2 among all the groups.The combined diagnostic model including H3.3G34W,p63 and SATB2 was established by Logistic regression analysis,and the diagnostic value of the model was evaluated by ROC curve analysis.Results The positive rates of H3.3G34W,p63 and SATB2 in GCTB group were 81.5%,90.7%and 92.6%,respectively;the positive rates in NGCTB group were 2.4%,28.9%and 62.7%.Compared with NGCTB group,the age of GCTB group was significantly older[(41.222±14.849)vs.(16.566±9.439),P<0.001],and the prevalence was higher in women than in men(51.9%vs.48.1%,P<0.001).In addition,compared with the NGCTB group,the positive rates of H3.3G34W(81.5%vs.2.4%,P<0.001),p63(90.7%vs.28.9%,P<0.001)and SATB2(92.6%vs.62.7%,P<0.001)were significantly higher in the GCTB group.Univariate regression analysis built a univariate prediction modeland ROC curve analysis showed that age(AUC=92.9%,P<0.001),sex(AUC=64.5%,P=0.004),H3.3G34W positive rate(AUC=89.5%,P<0.001),p63 positive rate(AUC=80.9%,P<0.001)and SATB2 positive rate(AUC=65.0%,P=0.003)were independent predictors of diagnosis of giant cell tumor of bone.Multivariate regression analysis(Logistic)constructed a hybrid prediction model.ROC curve analysis suggested that the hybrid model showed better prediction value than the single factor model(AUC=98.4%,P<0.001).Conclusion H3.3G34W,p63 and SATB2 are effective molecular markers for the diagnosis of GCTB,and their combined application can improve the prediction efficiency of the diagnosis of GCTB.
8.Pathogenesis and Treatment of Stomach Exuberance and Spleen Deficiency in Metabolic Disease
Wenxuan LUO ; Jinxi ZHAO ; Jinyan WEI ; Jiangteng LIU ; Zhichao RUAN ; Kaitong ZHANG ; Le WANG ; Weijun HUANG ; Yonghua XIAO
Journal of Traditional Chinese Medicine 2024;65(19):2041-2044
Stomach exuberance and spleen deficiency are common pathogenesis of many metabolic diseases. Through analyzing the pathogenesis of stomach exuberance and spleen deficiency, it is believed that its essence is stomach heat and spleen deficiency. Stomach heat includes gastrointestinal heat, spleen and stomach damp-heat, and spleen deficiency is divided into deficiency of spleen yin, deficiency of spleen qi , and deficiency of spleen yang. It is suggested that the metabolic diseases of stomach-exuberance and spleen-deficiency syndrome can be divided into three categories,i.e. stomach-heat and spleen yin-deficiency, stomach-heat and spleen qi-deficiency, and stomach-heat and spleen yang-deficiency, and the main treatment methods are clearing and draining heat, nourishing yin and moistening intestine, clearing dampness and heat, strengthening spleen and qi, clearing dampness and heat, strengthening spleen and warming yang, respectively, with prescriptions as Maziren Pills (麻子仁丸), Qinlian Pingwei Powder (芩连平胃散), and Jiawei Lianli Decoction (加味连理汤) accordingly.
9.Clinicopathological factors and clinical significance of No.12b lymph node metastasis in gastric antrum cancer
Bao ZHANG ; Guoliang ZHENG ; Yong ZHANG ; Yan ZHAO ; Haitao ZHU ; Tao ZHANG ; Yong LIU ; Zhichao ZHENG
Chinese Journal of Gastrointestinal Surgery 2024;27(2):167-174
Objective:To investigate the clinicopathological factors and clinical significance of (micro)metastasis in No.12b lymph node in patients with gastric antrum cancer.Methods:This was a retrospective cohort study of data of 242 patients with gastric adenocarcinoma without distant metastasis, complete follow-up data, and no preoperative anti-tumor therapy or history of other malignancies. All study patients had undergone radical gastrectomy (at least D2 radical range) + No.12b lymph node dissection in the Department of Gastric Surgery of Liaoning Cancer Hospital from January 2007 to December 2012. Immunohistochemical staining with antibody CK8/18 was used to detect micrometastasis to lymph nodes. Patients with positive findings on hematoxylin and eosin stained specimens and/or CK8/18 positivity in No.12b lymph node were diagnosed as having No.12b (micro)metastasis and included in the No.12b positive group. All other patients were classified as 12b negative. We investigated the impact of No.12b (micro)metastasis by comparing the clinicopathological characteristics and recurrence free survival (RFS) of these two groups of patients and subjecting possible risk factors to statistical analysis.Results:Traditional hematoxylin-eosin staining showed that 15/242 patients were positive for No.12b lymph nodes and 227 were negative. A total of 241 negative No. 12b lymph nodes were detected. Immunohistochemical testing revealed that seven of these 241 No.12b lymph nodes (2.9%) were positive for micrometastasis. A further seven positive nodes were identified among the 227 nodes (3.1%) that had been evaluated as negative on hematoxylin–eosin-stained sections. Thus, 22 /242 patients' (9.1%) No.12b nodes were positive for micrometastases, the remaining 220 (90.9%) being negative. Factor analysis showed that No.12b lymph node (micro) metastasis is associated with more severe invasion of the gastric serosa (HR=3.873, 95%CI: 1.676-21.643, P=0.006), T3 stage (HR=1.615, 95%CI: 1.113-1.867, P=0.045), higher N stage (HR=1.768, 95%CI: 1.187-5.654, P=0.019), phase III of TNM stage (HR=2.129, 95%CI: 1.102-3.475, P=0.046), and lymph node metastasis in the No.1/No.8a/No.12a groups (HR=0.451, 95%CI: 0.121-0.552, P=0.035; HR=0.645, 95%CI:0.071-0.886, P=0.032; HR=1.512, 95%CI: 1.381-2.100, P=0.029, respectively). Survival analysis showed that the 5-year RFS of patients in the No.12b positive group was worse than that of those in the No.12b negative group (18.2% vs. 34.5%, P<0.001). Independent predictors of RFS were poorer differentiation of the primary tumor (HR=0.528, 95%CI:0.288-0.969, P=0.039), more severe serous invasion (HR=1.262, 95%CI:1.039-1.534, P=0.019), higher T/N/TNM stage (HR=4.880, 95%CI: 1.909-12.476, P<0.001; HR=2.332, 95%CI: 1.640-3.317, P<0.001; HR=0.139, 95%CI: 0.027-0.713, P=0.018, respectively), and lymph node metastasis in the No.12a/No.12b group(HR=0.698, 95%CI:0.518-0.941, P=0.018; HR=0.341, 95%CI:0.154-0.758, P=0.008, respectively). Conclusion:Detection of micrometastasis can improve the rate of positive lymph nodes. In patients with gastric antrum cancer, dissection of group No.12b lymph nodes may improve the prognosis of those with intraoperative evidence of tumor invasion into the serosa, more than two lymph node metastases, and suspicious lymph nodes in groups No.1 / No.8a / 12a.
10.Overview of animal models of idiopathic inflammatory myopathy-associated interstitial lung disease
Zhichao LIU ; Xiaohe LI ; Honggang ZHOU ; Na ZHANG
Tianjin Medical Journal 2024;52(7):709-713
Idiopathic inflammatory myopathy(IIM)is a heterogeneous autoimmune disease of unknown etiology characterized by proximal limb muscle involvement and chronic inflammation.Multiple systems may be involved,with interstitial lung disease(ILD)being the most common manifestation of respiratory system involvement in IIM.This article summarizes the current methods of myositis animal models and myositis-associated ILD model construction methods,so as to provide reference for the subsequent construction and research of IIM-ILD models.


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