1.Syndrome Differentiation and Treatment Mechanisms of Inflammatory Injury in Diabetic Cardiomypathy from Theory of "Gaozhuo"
Xiaoyue WANG ; Yunfeng YU ; Xiangning HUANG ; Yixin XIANG ; Sihao ZHANG ; Qin XIANG ; Rong YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):235-244
Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM, the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion, and divides the pathological process into three phases: Gaozhuo invasion, turbid heat damage to the channels, and turbid blood stasis and heat junction. Among them, the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors, and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress, it eventually develops into a depletion of the heart Yang, leading to the ultimate regression of heart failure. According to the theory of Gaozhuo, traditional Chinese medicine (TCM) should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause, and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat, strengthening the spleen and tonifying the kidney, and clearing heat and resolving turbidity should be the therapy. If the turbidity, stasis, and heat are knotted in the heart and collaterals, strengthening the spleen and tonifying the kidney, and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity, benefiting Qi and clearing heat to resolve turbidity, and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors, improve the inflammatory damage to myocardium and blood vessels, myocardial fibrosis, and cardiac systole and diastole, and thus slow down the onset and progression of DCM.
2.Association of serum exosomal miR-122-5p with the prognosis of hepatic confluent necrosis and fibrosis in patients with chronic hepatitis B
Quanwei HE ; Ran XU ; Wei HAN ; Sihao WANG ; Yan CHEN ; Yongping YANG
Journal of Clinical Hepatology 2025;41(5):888-899
ObjectiveTo investigate the association of serum exosomal microRNAs (miRNAs) with hepatic inflammatory injury and histological outcomes in patients with chronic hepatitis B (CHB). MethodsPeripheral serum samples were collected from six healthy adults and six patients with CHB, and size exclusion chromatography was used to extract exosomes. Small RNA sequencing and transcriptomic analysis were used to identify the serum exosomal miRNAs associated with liver inflammatory injury and fibrosis, and quantitative real-time PCR was used for validation in a mouse model of acute liver injury induced by lipopolysaccharide/D-galactosamine, a rat model of liver fibrosis induced by carbon tetrachloride, and 84 CHB patients undergoing liver biopsy twice before and after treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups; an analysis of variance was used for comparison between multiple groups, and the Tukey test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the Kruskal-Wallis H test was used for comparison between multiple groups, and the Dunn test was used for further comparison between two groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Logistic regression analyses were used to investigate influencing factors. ResultsAbnormal expression of serum exosomal miR-122-5p was observed in patients with CHB, and it was downregulated in patients with confluent necrosis and advanced fibrosis. In the mouse model of acute liver injury and the rat model of liver fibrosis, compared with the control group, the model group had a significant reduction in the expression level of miR-122-5p in the liver (P=0.048 and 0.014), and compared with the patients with mild liver injury, the patients with severe confluent necrosis and advanced fibrosis showed a significant reduction in the expression level of miR-122-5p in liver tissue (P<0.05). Among the 84 CHB patients, the patients with severe hepatic confluent necrosis or advanced liver fibrosis had a significantly lower expression level of serum exosomal miR-122-5p than those with mild liver injury (P<0.001 and P=0.003). The multivariate Logistic regression analysis showed that the expression level of miR-122-5p was an independent influencing factor for confluent necrosis (odds ratio [OR]=0.001, 95% confidence interval [CI]: 0.000 — 0.037, P=0.005) and liver fibrosis degree (OR=0.568, 95%CI: 0.331 — 0.856, P=0.019). In addition, compared with the patients with low expression of miR-122-5p, the patients with high expression of miR-122-5p before treatment had a significantly higher reversal rate of liver fibrosis after 72 weeks of antiviral therapy (64.3% vs 38.1%, P=0.029). ConclusionSerum exosomal miR-122-5p in CHB patients is closely associated with the progression of hepatic confluent necrosis and fibrosis, and the reduction in the expression level of miR-122-5p may aggravate hepatic confluent necrosis, promote the progression of fibrosis, and affect the histological outcome of CHB patients after antiviral therapy.
3.Antisense oligonucleotides targeting IRF4 alleviate psoriasis.
Yanxia YU ; Yirui WANG ; Weiwei CHEN ; Chang ZHANG ; Zhuo LI ; Jing YU ; Minhao WANG ; Can SONG ; Sihao YAN ; Jiayi LU ; Liangdan SUN
Acta Pharmaceutica Sinica B 2025;15(7):3575-3590
Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4+ (CD4+) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 -/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4+ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.
4.Effect of Shortening PET/CT Acquisition Time on the Diagnosis of Parkinson's Disease
Jingwen LI ; Ruiyue ZHAO ; Yimin FU ; Lifu XU ; Sihao LIANG ; Xinlu WANG
Chinese Journal of Medical Imaging 2024;32(3):240-244
Purpose To investigate the effect of shortening the acquisition time of 18F-D6-AV133 PET/CT on image quality and diagnostic efficacy in Parkinson's disease.Materials and Methods A total of 51 participants(27 of Parkinson's disease,24 of healthy-controls)from the First Affiliated Hospital of Guangzhou Medical University from October 2021 to June 2022 were retrospectively selected.Images were obtained after the injection of the tracer 18F-D6-AV133(371.04±16.30)MBq for 60 min,with collection times of 10 min.Four sets of images were reconstructed using CT attenuation correction with acquisition times of 3,5,7 and 10 min.Semi-quantitative analysis was performed on the PET images,calculating the striatum-to-occipital lobe standardized uptake value ratio(SUVR).Two physicians independently conducted qualitative evaluations for each image group.The differences of SUVR and visual score results among four sets of images were performed.The optimal critical value of SUVR was obtained by analyzing the receiver operating characteristic curve of the subjects.Results The visual analysis of image quality had a strong consistency between the two doctors(ICC=0.853,P<0.001).The images with acquisition time of 5 min could reach the common quality level in clinical work,accounting for 78.4%(40/51).The semi-quantitative results of image quality showed that there was no significant difference between SUVR and diagnostic efficiency obtained by acquisition time 5 min and 10 min(Z=1.821,P=0.069),and the best critical value of the two groups was equal to 3.Therefore,properly shortening the acquisition time had no effect on the diagnosis of Parkinson's disease.Conclusion With the development and advancement of technical equipment,PET image quality is gradually improving and the scanning time is also gradually shortening.The acquisition time for 18F-D6-AV133 can be shortened from the conventional 10 min to 5 min.
5.Regulation of GS and GLS expression by c-myc in oral epidermoid carcinoma cells and in tumor growth in nude mice
Qianqian ZHANG ; Sihao LIU ; Yali GUO ; Tao WANG
Journal of Practical Stomatology 2024;40(1):26-30
Objective:To explore the correlation between c-myc and glutaminase(GLS)and glutamine synthase(GS)in oral epider-moid carcinoma cells in animal models.Methods:Immunohistochemistry was used to detect the expression of c-myc,GLS and GS in clinical samples of oral cancer.KB cell model with stable and high expression of c-myc was established and verified,then the KB cells were transplanted into nude mice to establish mouse tumorigenic models.The cells and nude mouse models were respectively diveded into 3 groups(n=6):normal cotnrol,empty vector and c-myc overexpression groups.The tumor growth was observed.The expression of c-myc,GLS and GS in the cells and the tumor samples was detected by immunohistochemistry.Results:c-myc,GLS and GS were highly expressed in clinical samples of oral cancer.In the cells of c-myc overexpression group c-myc mRNA expression level was sig-nificantly higher than that of empty vector control group.The tumorigenic models were formed in all nude mice of the groups,and the volume and weight of the c-myc overexpression group increased more significantly(P<0.01),in the c-myc overexpression group c-myc was overexpressed,the expression of GLS and GS was significantly higher than that in the other 2 groups.Conclusion:c-myc is highly expressed in oral cancer,and may up-regulate GLS and GS expression.
6.Application value of 18F-D3FSP PET/CT in patients with cognitive impairment of varying degrees
Sihao LIANG ; Anqi LI ; Ruiyue ZHAO ; Jingwen LI ; Peng HOU ; Shuang XIONG ; Zhuohua WU ; Xiang CHEN ; Yuying HUANG ; Tengfei GUO ; Xinlu WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(5):260-265
Objective:To explore the effectiveness of 18F-deuterated-Florbetapir (D3FSP) PET/CT imaging in detecting β-amyloid (Aβ) deposition in the brain and its correlation with plasma biomarkers. Methods:A retrospective analysis was conducted on 79 patients (32 males, 47 females; age(66±7)years) who underwent 18F-D3FSP PET/CT imaging from June 2022 to November 2023 at the First Affiliated Hospital, Guangzhou Medical University, as a part of the Greater Bay Area Healthy Aging Brain Longitudinal Cohort Study (GHABS). Based on the Alzheimer′s Disease Neuroimaging Initiative cohort standard protocol, patients were categorized into cognitively unimpaired (CU) group, mild cognitive impairment (MCI) group, and Alzheimer′s disease (AD) group. Brain regions were segmented using the AW workstation and the SUV ratio (SUVR) was calculated with the cerebellum as the reference region. One-way analysis of variance, Bonferroni correction and Pearson correlation analysis were used to analyze data. The ROC curve analysis was used to analyze the cut-off value and the diagnostic efficacy of SUVR. Results:There were 48, 15 and 16 cases in CU, MCI and AD groups respectively. During the transition from CU to MCI and then to AD, there was a rising trend in SUVR ( F values: 11.15-22.38, all P<0.001) across the whole brain and various brain regions (bilateral frontal lobes, bilateral anterior cingulate gyrus, bilateral precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes). SUVRs of the right anterior cingulate gyrus and bilateral precuneus were different between the CU and MCI groups (all P<0.017), and those of bilateral frontal lobes, right precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes were different between the MCI and AD groups (all P<0.017). SUVRs of brain regions were negatively correlated with cognitive scale scores ( r values: from -0.57 to -0.37, all P<0.001), and were positively correlated with plasma phosphorylated tau181 (p-tau181, r values: 0.50-0.61, all P<0.001). The ROC curve analysis suggested that the cut-off value of SUVR in the precuneus for distinguishing CU from AD was 1.20, with the AUC, sensitivity, specificity and accuracy of 0.85, 12/16, 91.7%(44/48)and 87.5%(56/64), respectively. Conclusion:18F-D3FSP PET/CT imaging has good clinical application value in assessing the deposition sites and the extent of Aβ in the brain, which is related to clinical cognition and plasma p-tau181 level.
7.Analysis on clinical efficacy of anterior cervical Hybrid surgery and posterior cervical expansive open-door laminopasty for multilevel cervical spondylotic myelopathy
Lixiang WANG ; Chungen LI ; Genzhe LIU ; Ziyi ZHAO ; Sihao ZHAO ; Chao CHEN ; Yonggang ZHU ; Wei LI
Journal of Jilin University(Medicine Edition) 2024;50(1):228-235
Objective:To analyze the efficacy of anterior cervical Hybrid surgery and posterior cervical expansive open-door laminoplasty(EODL)in the treatment of multilevel cervical spondylotic myelopathy,and to discuss the selection of surgical methods for the patients with multilevel cervical spondylotic myelopathy.Methods:The retrospective analysis was conducted of 70 patients with multilevel cervical spondylotic myelopathy who underwent surgery at Affilated Beijing Traditional Chinese Medicine Hospital of Capital Medical University from July 2017 to July 2020.Based on the different surgical methods,the patients were divided into anterior group(n=35)and posterior group(n=35).The patients in anterior group underwent Hybrid surgery[anterior cervical discectomy and fusion(ACDF)combined with artificial cervical disc replacement(ACDR)],and the patients in posterior group underwent EODL.The hospitalization time,operation time,intraoperative blood loss,and postoperative drainage volume of the patients in two groups were recorded;the efficacy was evaluated by Japanese orthopaedic association(JOA)score,JOA improvement rate,neck disability index(NDI),visual analogue scale(VAS)for pain,and postoperative satisfaction score;the complications of the patients in two groups after surgery were recorded.Results:Compared with posterior group,the intraoperative blood loss,postoperative drainage volume,hospitalization time,and operation time of the patients in anterior group were significantly decreased(P<0.01),and the preoperative score had no significant difference(P>0.05).At the final follow-up after surgery,compared with posterior group,the JOA score and JOA improvement rate of the patients in anterior group were significantly increased(P<0.01),and the NDI score and VAS score were significantly decreased(P<0.01).Compared with before surgery,the JOA scores of the patients in two groups at the final follow-up after surgery were increased(P<0.01),and the NDI and VAS scores were significant decreased(P<0.01).The postoperative satisfaction of the patients in two groups was high based on the postoperative satisfaction score.There was no significant difference in the incidence of postoperative complication of the patients between two groups(P>0.05).Conclusion:Both the anterior cervical Hybrid surgery and EODL achieve the satisfactory results in the treatment of multilevel cervical spondylotic myelopathy.Hybrid surgery has the advantages of less bleeding and shorter surgery time,and the most suitable surgical method should be chosen clinically based on the actual situation of the patients.
8.Efficacy of total laparoscopic radical cystectomy with intracorporeal ileal conduit urinary diversion: a report of 25 cases
Sihao WANG ; Bohan FAN ; Yue XU ; Liming SONG ; Xiaoguang ZHOU ; Xiaopeng HU ; Wei WANG
Journal of Modern Urology 2024;29(4):312-316
【Objective】 To investigate the efficacy and surgical technique of total laparoscopic radical cystectomy with intracorporeal ileal conduit urinary diversion, so as to provide reference for the selection of surgery for patients with bladder cancer. 【Methods】 Clinical data of 48 patients with bladder cancer who underwent laparoscopic radical cystectomy during Mar.2017 and Aug.2022 in our hospital were retrospectively analyzed, including 23 cases who received traditional laparoscopic radical cystectomy combined with extracorporeal ileal conduit, and 25 who received total laparoscopic radical cystectomy with intracorporeal ileal conduit.The operation time, blood loss, postoperative intestinal function recovery time, drainage tube removal time and hospital stay were compared between the two groups. 【Results】 All procedures were successfully performed, and no Clavien-Dindo>grade 3 complications were observed.The operation time, and amount of estimated blood loss of the traditional group and total laparoscopic radical group were (227.0±46.4) min vs. (253.6±58.9) min, and (131.7±79.8) mL vs. (154.0±93.0) mL, respectively.There were no differences in postoperative intestinal function recovery time and drainage tube removal time (P>0.05).The hospital stay was shorter in the total laparoscopic radical group than in the traditional group (P=0.035). 【Conclusion】 Total laparoscopic radical cystectomy with intracorporeal ileal conduit urinary diversion is safe and feasible.which is comparable to the traditional laparoscopic surgery, while the hospital stay in the total laparoscopic group is shorter, which is conducive to rapid postoperative recovery.
9.Construction of a risk warning model for acute lung injury caused by Staphylococcus aureus infection
Jiaojiao SUN ; Tian WANG ; Xiaolin LI ; Sihao JIN ; Shengpeng LI ; Jianjun CHU ; Zhiqiang WANG
Chinese Journal of Infectious Diseases 2023;41(5):338-343
Objective:To investigate the risk factors of acute lung injury (ALI) caused by Staphylococcus aureus infection, and to construct a risk warning model. Methods:Patients with Staphylococcus aureus infection confirmed by sputum or blood culture admitted to the Affiliated Hospital of Jiangnan University from January 1, 2020 to May 10, 2022 were enrolled and divided into ALI group and non-ALI group. The age, smoking status, C-reactive protein (CRP), procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), albumin, oxygenation index and other clinical data were compared between the two groups. Univariate analysis was performed by using independent sample t test and chi-square test. Binary logistic regression analysis was used to screen the independent risk factors of ALI caused by Staphylococcus aureus infection, and a risk warning model was constructed. The receiver operator characteristic (ROC) curve was used to evaluate the predictive ability of the model. Results:There were 96 cases of Staphylococcus aureus infection, including 68 cases (70.8%) in ALI group, of which 41 cases (60.3%) were positive in sputum culture and 27 cases (39.7%) were positive in blood culture. Compared with the non-ALI group, the proportion of patients aged ≥60 years in ALI group was lower (58.8%(40/68) vs 64.3%(18/28)), the proportion of smoking was higher (58.8%(40/68) vs 35.7%(10/28)), and the differences were both statistically significant ( χ2=0.76 and 0.03, respectively, both P<0.05). The levels of CRP, PCT and NLR in the ALI group were all higher than those in non-ALI group, while oxygenation index and albumin level were both lower, and the differences were all statistically significant ( t=-5.28, -3.46, -9.87, 12.83 and 3.08, respectively, all P<0.05). Binary logistic regression analysis showed that CRP (odds ratio ( OR)=1.973, 95% confidence interval (95% CI) 0.956 to 2.989), PCT ( OR=3.734, 95% CI 1.014 to 13.746), NLR ( OR=1.152, 95% CI 1.058 to 2.254) and albumin ( OR=1.527, 95% CI 1.110 to 2.102) were independent risk factors for ALI caused by Staphylococcus aureus infection. The areas under the ROC curve of CRP, PCT, NLR, albumin and the risk warning model constructed from the combination of four risk factors were 0.69, 0.81, 0.83, 0.78 and 0.93, respectively. The sensitivities were 65.14%, 89.91%, 84.40%, 56.88% and 98.17%, respectively. The specificities were 62.37%, 60.22%, 65.59%, 80.64% and 93.55%, respectively. The accuracy of the effectiveness test of the risk warning model was 84.97%. Conclusions:CRP, PCT, NLR and albumin are the independent risk factors for ALI caused by Staphylococcus aureus infection. The risk warning model based on the above factors has a good early warning effect on ALI caused by Staphylococcus aureus infection.
10.Review on non-surgical treatment for elderly patients with locally advanced head and neck squamous cell carcinoma
Shanshan HE ; Churong LI ; Sihao CHEN ; Shilong SHAO ; Zuxian ZHONG ; Dan WANG ; Yi LIU ; Shichuan ZHANG
Chinese Journal of Radiation Oncology 2023;32(2):169-173
With the aging of population, the elderly (≥65 years old) cancer patients have become one of the main populations for cancer care. For inoperable locally advanced head and neck squamous carcinomas, cisplatin-based concurrent chemoradiotherapy is the first-line choice. Several large clinical studies have shown that patients under 70 years of age can still benefit from concurrent chemoradiotherapy, while it should be cautious to apply chemotherapy to patients aged 70-80 years. For elderly patients who are intolerant to cisplatin, carboplatin or other regimens with less gastrointestinal and renal toxicity should be considered. Although anti-epidermal growth factor receptor (EGFR) monoclonal antibodies combined with radiotherapy has been proved to be more effective than radiotherapy alone in total patient population, age-subgroup analysis showed limited benefit in elderly patients. The safety of immune checkpoint inhibitors in elderly patients has been validated and those with high programmed death ligand-1 (PD-L1) expression may benefit from concurrent or neoadjuvant immunotherapy, however, high-level evidence is still lacking. For patients older than 80 years, radiotherapy alone may be superior to concurrent chemoradiotherapy, and hypofractionated radiotherapy for palliative purposes can be safely used in this population.

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