1.Alleviation of Ulcerative Colitis by Shaoyaotang via Inhibiting Glycolysis Through SIRT6/HIF-1α Pathway
Yiling XIA ; Hui CAO ; Dongsheng WU ; Bo ZOU ; Erle LIU ; Yiwen WANG ; Shaijin JIANG ; Yiqian YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):10-19
ObjectiveTo investigate the role of silent information regulatory protein (SIRT6)/hypoxia-inducible factor-1α (HIF-1α) pathway in regulating the reprogramming of glucose metabolism in ulcerative colitis (UC) and the mechanism of intervention of Shaoyaotang. MethodsForty-eight c57bL/6 mice were randomly divided into a blank group, a model group, a Mesalazine group (0.42 g·kg-1), a Shaoyaotang group (31.08 g·kg-1), an inhibitor group (OSS-128167, 50 mg·kg-1), and an inhibitor + Shaoyaotang group (50 mg·kg-1 OSS-128167 + 31.08 g·kg-1 Shaoyaotang). A UC model was established by the administration of 2.5% dextran sulfate sodium (DSS) solution for mice in other groups for 7 d, except for the blank group. The mice in each group were treated with saline, Mesalazine, Shaoyaotang, inhibitor, and inhibitor + Shaoyaotang, respectively, for 7 d. The mice were necropsied 24 h after the last administration of the drug. The blood was collected from the orbital region, and colon tissue was taken. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in colon tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect serum interleukin (IL)-10, IL-17, and IL-6 levels. A biochemical method was used to detect glucose and lactate dehydrogenase A (LDHA) levels. Immunohistochemistry (IHC) was employed to detect IL-22 and transforming growth factor-β1 (TGF-β1) levels in colon tissue, and Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect relative protein and mRNA expressions of SIRT6, HIF-1α, and LDHA. ResultsCompared with those of the blank group, disease activity index (DAI) scores of mice in the model group and inhibitor group were significantly increased (P<0.01). The length of colon tissue was significantly shortened, and colon tissue was congested and eroded. The pathohistological scores were significantly increased (P<0.01). The levels of serum inflammatory factors IL-17 and IL-6 were significantly elevated, and the levels of IL-10 were significantly decreased (P<0.01). The protein expressions of IL-22 and TGF-β1 were significantly reduced in colon tissue (P<0.01). The relative protein and mRNA expressions of SIRT6 were significantly decreased (P<0.01), and the relative protein and mRNA expressions of HIF-1α and LDHA and the contents of glucose and lactate were significantly elevated (P<0.01). The level of inflammation in the colon of the mice in the inhibitor group was more severe than that in the model group (P<0.01). Compared with the model group, the Mesalazine group, the Shaoyaotang group, and the inhibitor + Shaoyaotang group showed reduced colonic injury, significant decrease in serum IL-17 and IL-6, significant increase in IL-10 (P<0.01), significant increase in the protein expressions of IL-22 and TGF-β1 in colon tissue (P<0.01), significant increase in the protein expressions of SIRT6 and the relative mRNA expressions (P<0.01), and significant reduction in the protein expressions of HIF-1α and LDHA, the relative mRNA expressions, and the contents of glucose and lactate (P<0.01). Compared with those in the Shaoyaotang group, the serum IL-17 and IL-6 were significantly increased, and IL-10 was significantly decreased in the inhibitor + Shaoyaotang group (P<0.01). The protein expressions of IL-22 and TGF-β1 in colon tissue were significantly decreased (P<0.01). The expressions of SIRT6 protein and the relative mRNA expressions were significantly decreased (P<0.01). The protein expressions of HIF-1α and LDHA, the relative mRNA expressions, and the contents of glucose and lactate were significantly elevated (P<0.01). However, the difference between the Shaoyaotang group and the Mesalazine group was not significant. ConclusionShaoyaotang can effectively treat DSS-induced mice with UC through the SIRT6/HIF-1α pathway, and its mechanism of action may be related to the regulation of the SIRT6/HIF-1α pathway and glucose metabolism reprogramming and the inhibition of glycolysis.
2.Alleviation of Ulcerative Colitis by Shaoyaotang via Inhibiting Glycolysis Through SIRT6/HIF-1α Pathway
Yiling XIA ; Hui CAO ; Dongsheng WU ; Bo ZOU ; Erle LIU ; Yiwen WANG ; Shaijin JIANG ; Yiqian YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):10-19
ObjectiveTo investigate the role of silent information regulatory protein (SIRT6)/hypoxia-inducible factor-1α (HIF-1α) pathway in regulating the reprogramming of glucose metabolism in ulcerative colitis (UC) and the mechanism of intervention of Shaoyaotang. MethodsForty-eight c57bL/6 mice were randomly divided into a blank group, a model group, a Mesalazine group (0.42 g·kg-1), a Shaoyaotang group (31.08 g·kg-1), an inhibitor group (OSS-128167, 50 mg·kg-1), and an inhibitor + Shaoyaotang group (50 mg·kg-1 OSS-128167 + 31.08 g·kg-1 Shaoyaotang). A UC model was established by the administration of 2.5% dextran sulfate sodium (DSS) solution for mice in other groups for 7 d, except for the blank group. The mice in each group were treated with saline, Mesalazine, Shaoyaotang, inhibitor, and inhibitor + Shaoyaotang, respectively, for 7 d. The mice were necropsied 24 h after the last administration of the drug. The blood was collected from the orbital region, and colon tissue was taken. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in colon tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect serum interleukin (IL)-10, IL-17, and IL-6 levels. A biochemical method was used to detect glucose and lactate dehydrogenase A (LDHA) levels. Immunohistochemistry (IHC) was employed to detect IL-22 and transforming growth factor-β1 (TGF-β1) levels in colon tissue, and Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect relative protein and mRNA expressions of SIRT6, HIF-1α, and LDHA. ResultsCompared with those of the blank group, disease activity index (DAI) scores of mice in the model group and inhibitor group were significantly increased (P<0.01). The length of colon tissue was significantly shortened, and colon tissue was congested and eroded. The pathohistological scores were significantly increased (P<0.01). The levels of serum inflammatory factors IL-17 and IL-6 were significantly elevated, and the levels of IL-10 were significantly decreased (P<0.01). The protein expressions of IL-22 and TGF-β1 were significantly reduced in colon tissue (P<0.01). The relative protein and mRNA expressions of SIRT6 were significantly decreased (P<0.01), and the relative protein and mRNA expressions of HIF-1α and LDHA and the contents of glucose and lactate were significantly elevated (P<0.01). The level of inflammation in the colon of the mice in the inhibitor group was more severe than that in the model group (P<0.01). Compared with the model group, the Mesalazine group, the Shaoyaotang group, and the inhibitor + Shaoyaotang group showed reduced colonic injury, significant decrease in serum IL-17 and IL-6, significant increase in IL-10 (P<0.01), significant increase in the protein expressions of IL-22 and TGF-β1 in colon tissue (P<0.01), significant increase in the protein expressions of SIRT6 and the relative mRNA expressions (P<0.01), and significant reduction in the protein expressions of HIF-1α and LDHA, the relative mRNA expressions, and the contents of glucose and lactate (P<0.01). Compared with those in the Shaoyaotang group, the serum IL-17 and IL-6 were significantly increased, and IL-10 was significantly decreased in the inhibitor + Shaoyaotang group (P<0.01). The protein expressions of IL-22 and TGF-β1 in colon tissue were significantly decreased (P<0.01). The expressions of SIRT6 protein and the relative mRNA expressions were significantly decreased (P<0.01). The protein expressions of HIF-1α and LDHA, the relative mRNA expressions, and the contents of glucose and lactate were significantly elevated (P<0.01). However, the difference between the Shaoyaotang group and the Mesalazine group was not significant. ConclusionShaoyaotang can effectively treat DSS-induced mice with UC through the SIRT6/HIF-1α pathway, and its mechanism of action may be related to the regulation of the SIRT6/HIF-1α pathway and glucose metabolism reprogramming and the inhibition of glycolysis.
3.Development and evaluation of a triplex RT-qPCR assay with internal references for detection of the Dengue and Zika viruses
Meng-Tao CAO ; Xiao-Yu HU ; Wei YANG ; Chun-Yuan LI ; Xiao-Li XU ; Rui-Wen REN ; Hong-Xia JIANG
Chinese Journal of Zoonoses 2024;40(6):537-543
A triplex RT-qPCR assay with human genes as internal references was established for detection of the Dengue and Zika viruses(DENV and ZIKV,respectively).The conserved regions of the four serotypes of DENV,along with the NS1 gene of ZIKV and the human β-actin gene,which is stably ex-pressed in various human tissues,were targeted by three sets of specific primers and probes.Standard plasmids for four se-rotypes of DENV,ZIKV,and β-actin were constructed as pos-itive controls.Optimal reaction conditions were determined through an L9(34)orthogonal experiment.The specificity,sensitivity,and coverage of the assay were verified and evalua-ted clinically,and the consistency was evaluated against a com-mercial kit for detection of DENV.The triplex RT-qPCR assay established exhibited no non-specific cross reactions with 12 similar arboviruses.The detection sensitivity for DENV and ZIKV were 2.99 and 2.18 copies/μL,respectively,and the intra-group and inter-group repeatability coefficients of variation were within 1.5%.As compared to the commercial kit,the proposed assay obtained positive results for 13 epidemic strains of DENV.Bland-Altman consistency analysis confirmed that the consistency of the detection results of clinical positive samples between the commercial kit and the proposed assay was 92.59%.The highly specific and sensitive triplex RT-qPCR assay with internal references is an effective tool for early and rapid differential identification of DENV and ZIKV.
4.Comparison of Blood Oxygen Saturation Detection Methods in Patients with Hyperleukocytic Acute Leukemia
Hui-Xia GUO ; Shu-Ya CAO ; Yi-Juan CHEN ; Qian LI ; Yue WU ; Yu-Xi SHANG ; Li-Ru WANG
Journal of Experimental Hematology 2024;32(4):1026-1031
Objective:To investigate which indicator is more advantageous when using arterial oxygen saturation(SaO2)and fingertip pulse oxygen saturation(SpO2)for blood oxygen detection in patients with hyperleukocytic acute leukemia(HAL).Methods:In this prospective research,the difference between SaO2 and SpO2 of 18 HAL patients(observation group)and 14 patients(control group),as well as the relationship between the difference and white blood cell(WBC)counts were analyzed.Results:SaO2 was lower than SpO2 in the observation group(P<0.05),and SpO2-SaO2 difference was positively correlated with WBC counts(r=0.47).However,there was no statistical difference between SaO2 and SpO2 in the control group.SaO2 and PO2 showed a downward trend with the prolongation of detection time after arterial blood was collected in the observation group,but there was no statistical difference.There was no downward trend of SaO2 and PO2 in the control group.Conclusion:HAL patients have a phenomenon where SaO2 is lower than SpO2,that is pseudohypoxemia,and this phenomenon may be caused by excessive consumption of oxygen by the leukemia cells in vitro.SpO2 can be monitored bedside in real time and is non-invasive,it is a better way to detect the blood oxygen status of HAL patients.
5.Imaging assessment of the activity and treatment efficacy of thyroid associated ophthalmopathy
Yu LIU ; Mengting LI ; Hong CHEN ; Wei LIU ; Ying DING ; Li ZHANG ; Yinqian DENG ; Huanyu CHEN ; Min ZHAO ; Xiaotian XIA ; Wei CAO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(10):628-632
Thyroid associated ophthalmopathy (TAO) is an organ-specific autoimmune disease. TAO is clinically classified into active and inactive stage, and the accurate judgment is the key point of treatment choice. Clinical activity score (CAS) is often used for the assessment of TAO activity, which is subjective to some extent. With the development of imaging techniques, ultrasonography, CT, MRI and radionuclide imaging have gradually been applied into the diagnosis and treatment of TAO. What′s more, the imaging is an important complement to CAS from the aspects of anatomical and functional metabolism, which can better assess the activity and the therapy response of TAO. The clinical value of medical imaging in activity and treatment efficacy evaluation of TAO is reviewed in this article.
6.Ameliorative effects of Liangxue Heying Formula on vascular inflammatory injury in a rat model of thromboangiitis obliterans via JAK2/STAT3 signaling pathway
Xia FENG ; Yu-Zhen WANG ; Yan-Dan ZHU ; Cheng ZHAO ; Ji LI ; Ye-Min CAO
Chinese Traditional Patent Medicine 2024;46(9):2915-2922
AIM To study the effects of Liangxue Heying Formula on vascular inflammatory injury in a rat model of thromboangiitis obliterans(TAO).METHODS The rats were randomly divided into the sham operation group,the model group and the low,medium and high dose Liangxue Heying Formula groups(2.25,4.5,9 g/kg).With the rat TAO model successfully established by injection of 0.1 mL sodium laurate(10 mg/mL)into the femoral artery of hind limbs,corresponding doses of drugs by gavage were administered upon the rats.Subsequently,the rats had their morphological changes of the affected limbs observed and assessed;their changes of blood flow in hind limbs scanned by laser Doppler flowmetry;their plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1 detected by ELISA;their histopathological changes of femoral artery and vein observed by HE staining;and their protein expressions of TNF-α,IL-6,JAK2,p-JAK2,STAT3,p-STAT3,ICAM-1 and VCAM-1 in femoral artery detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased morphological score of the affected limb(P<0.01);decreased blood perfusion ratio of the affected side/healthy side(P<0.01);increased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P<0.01);more existence of thrombotic infiltration containing a larger number of inflammatory cells in femoral artery and femoral vein tissue,and increased protein expressions of TNF-α,IL-6,p-JAK2,p-STAT3,ICAM-1 and VCAM-1 in femoral artery(P<0.01).Compared with the model group,the medium and high dose Liangxue Heying Formula groups demonstrated decreased morphological score of the affected limb(P<0.01);increased blood perfusion ratio of the affected side/healthy side(P<0.01);reduced infiltration of thrombus and inflammatory cells in femoral artery and femoral vein tissue,and decreased protein expressions of IL-6 and p-STAT3 in femoral artery tissue(P<0.01).All Liangxue Heying Formula groups shared decreased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P<0.05,P<0.01);and reduced protein expressions of TNF-α,ICAM-1,VCAM-1 and p-JAK2 in femoral artery(P<0.01).CONCLUSION Liangxue Heying Formula can improve the systemic inflammatory state of TAO rats by inhibiting the activation of endothelial cells and reducing vascular inflammatory injury possibly due to the mechanism associated with the regulation of the JAK2/STAT3 signaling pathway.
7.Rare VPS33B gene mutation combined with GP1BA mutation causes severe decrease in plasma VWF levels: a case report and literature review
Siqian MA ; Xia BAI ; Lijuan CAO ; Zhenni MA ; Zixuan DING ; Ziqian YU ; Miao JIANG
Chinese Journal of Hematology 2024;45(6):602-605
A 28-year-old woman was found to have coagulation factor Ⅷ activity (FⅧ∶C) <1% and von Willebrand factor antigen (VWF∶Ag) <1% during routine prenatal examinations. No pathogenic variation was found in the exon region of the VWF gene using next-generation sequencing. The clinical presentation of this patient does not match the clinical characteristics of type Ⅲ hemophilia [von Willebrand disease (VWD) ]; therefore, third-generation sequencing technology was used to perform whole-genome sequencing on the patient and her family members. Multiple members of the patient’s paternal family carried a heterozygous variant of VPS33B, c.869G>C. The family members carrying this variant all had varying degrees of reduced VWF levels (39% -56% ). Moreover, the proband was detected with the heterozygous variant c.1474dupA in GP1BA. The ACMG and Clinvar databases determined that this variation was associated with platelet-type pseudo VWD. The decrease in VWF levels caused by heterozygous variations in VPS33B in families is the first international report, and no previous studies have reported cases of severe decrease in plasma VWF levels caused by double heterozygous variations in VPS33B and GP1BA.
8.Dosimetric effect of calculation grid size on stereotactic body radiation therapy of lung cancer in helical tomotherapy planning system
Xia-Yu HANG ; Wan-Rong JIANG ; Yi-Kun LI ; Jun HU ; Yan ZHANG ; Ruo-Qi CAO ; Nan XU ; Lei WANG ; Jin-Da ZHOU ; Xiang-Dong SUN
Chinese Medical Equipment Journal 2024;45(2):52-57
Objective To investigate the dosimetric effects of different calculation grid size(CGS)in helical tomotherapy(HT)planning system on stereotactic body radiation therapy(SBRT)for non-small cell lung cancer(NSCLC).Methods Nine NSCLC patients receiving radiation therapy for the first time at some hospital from March 2019 to December 2022 were selected as the subjects.SBRT planning was carried out through the HT system with three different CGS plans(Fine,Normal,and Coarse)and the same pitch,modulation factor(MF)and optimization conditions,and the target area indexes of the three CGS plans were compared including conformity index(CI),homogeneity index(HI),dosimetric parameters of the organ at risk(OAR),point dose verification pass rate,treatment time,number of monitor units and Sinograms.SPSS 22.0 was used for statistical analysis.Results For target area HI,there weres significant differences between CGS Fine plan and Coarse plan and between CGS Normal plan and Coarse plan(P<0.05),while no statistical differences were found between CGS Fine plan and Normal plan(P>0.05).For target area CI,there were significant differences between CGS Fine plan and Coarse plan(P<0.05),while no statistical differences were found between CGS Fine plan and Normal plan and between CGS Normal plan and Coarse plan(P>0.05).For OAR dosimetric parameters,CGS Fine plan and Coarse plan had significant differences in heart Dmax and Dmean,esophageal Dmax and Dmean,V5,V20,V30 and Dmean of the whole lung and affected lung,V5 and Dmax of the affected lung and heart V10 and V30(P<0.05),CGS Normal plan and Coarse plan had obvious differences in esophageal Dmax(P<0.05),and the remained dosimetric parameters were not statistically significant(P>0.05).Fine,Normal and Coarse plans had the point dose verifica-tion pass rates being 0.96%,1.50%and 1.77%,respectively.In terms of treatment time and number of monitor units,there were significant differences between Fine plan and Coarse plan(P<0.05)while no statistical differences were found between Fine and Normal plans and between Normal and Coarse plans(P>0.05).Sinograms analyses showed Fine plan had evenly distributed segment color gradient,Coarse plan had areas of very dark and very light color gradients and Normal plan was somewhere in between.Conclusion Low CGS has to be used as much as possible to obtain accurate dose distribution during SBRT planning for NSCLC patients,which contributes to the execution of the radiation therapy plan and the prevention of ad-verse effects.[Chinese Medical Equipment Journal,2024,45(2):52-57]
9.Dosimetric effect of jaw widths on stereotactic body radiotherapy for hepatocellular carcinoma
Xia-Yu HANG ; Yi-Kun LI ; Jun HU ; Ruo-Qi CAO ; Yan ZHANG ; Nan XU ; Xian-Qiang SONG ; Xiang-Dong SUN
Chinese Medical Equipment Journal 2024;45(7):51-55
Objective To investigate the radiotherapy dose impacts of different jaw widths on stereotactic body radiotherapy(SBRT)for hepatocellular carcinoma(HCC)with the hilical tomotherapy(HT)planning system.Methods Totally 16 HCC patients who received radiotherapy at some hospital from March 2021 to August 2023 were selected,and the planning was carried out with the same pitch,modulation factors and optimization conditions and the jaw widths being 1.0,2.5 and 5.0 cm.The dosimetric differences due to the jaw widths in planned targets and organs at risk(OAR)were compared,and the planned treatment time,monitor unit,gantry rotations and gantry period were evaluated.SPSS 22.0 was used for statistical analysis.Results Better dosimetric parameters and lower doses to OARs could be got with lower jaw widths.The widened jaw widths resulted in reduced planned treatment time,decreased monitor units and gantry rotations,shortened gantry period while enhanced treatment efficiency.Conclusion A 2.5 cm jaw width for HT planning contributes to improving treatment efficiency during HCC SBRT under the premise of ensured target dose distribution and satisfactory dose to OAR for clinical require-ments.[Chinese Medical Equipment Journal,2024,45(7):51-55]
10.PD-1 inhibitors plus chemotherapy for refractory EBV-positive DLBCL:a retrospective analysis
Youli LI ; Yonghe WU ; Sufen CAO ; Baohua YU ; Qunling ZHANG ; Zuguang XIA ; Junning CAO ; Fangfang LV ; Guang‑Liang CHEN
Blood Research 2024;59():36-
Background:
Immunochemotherapy has demonstrated a promising efficacy for a variety of B-cell lymphoma but has limited efficacy for Epstein–Barr virus-positive (EBV +) diffuse large B-cell lymphoma (DLBCL) that is refractory or relapsed to conventional chemotherapy regimens. Considering higher programmed death-ligand 1 (PD-L1) expres‑ sion in the subset of patients with DLBCL with positive EBV, we speculated that PD-1 inhibitors plus chemotherapy may be an alternative regimen in patients with refractory/relapsed EBV + DLBCL.
Methods:
This retrospective study included six adult patients diagnosed with refractory EBV + DLBCL resistant to first-line immunochemotherapy regimens (R-CHOP). These patients received PD-1 inhibitors plus chemotherapy as second-line treatment.
Results:
The final analysis included six patients (four men and two women (median age, 50 years; range, 39–83 years)). Four patients were diagnosed with Epstein–Barr virus (EBV) + DLBCL, and two had DLBCL associated with chronic inflammation. Over a median follow-up of 20 months (range, 2–31 months), the objective response rate was 83% (5/6) and the complete remission rate was 67% (4/6). No severe immune-related adverse reactions occurred, and only a mild rash was reported, which did not necessitate the discontinuation of therapy.
Conclusion
The combination of PD-1 inhibitors and chemotherapy offers promising results as a second-line treat‑ ment for patients with refractory EBV + DLBCL that is resistant to first-line immunochemotherapy regimens. These preliminary findings warrant further investigation in larger clinical trials to validate the efficacy and safety of this therapeutic approach.

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