1.Effects of Xiaozhong Zhitong Mixture (消肿止痛合剂) on Angiogenesis and the Dll4/Notch1 Signaling Pathway in Wound Tissue of Diabetic Foot Ulcer Model Rats
Xiao HAN ; Tao LIU ; Yuan SONG ; Jie CHEN ; Jiaxuan SHEN ; Jing QIAO ; Hengjie WANG ; Lewen WU ; Yazhou ZHAO
Journal of Traditional Chinese Medicine 2025;66(16):1695-1703
ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture (消肿止痛合剂, XZM) in the treatment of diabetes foot ulcer (DFU). MethodsFifty SD rats were randomly divided into blank group, model group, XZM group, inhibitor group, XZM plus inhibitor group (combination group), with 10 rats in each group. Except for the blank group, rats were fed with high-sugar, high-fat, high-cholesterol diet, intraperitoneally injected with streptozotocin, and subjected to skin defect to establish DFU model. After successful modeling, the XZM group and the combination group were given 1 ml/(100 g·d)of XZM by gavage, while the blank group, model group, and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later, the inhibitor group and the combination group were intraperitoneally injected with 5 mg/(kg·d) of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration, the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin (HE) staining. The microvascular density (MVD) in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction (RT-PCR) and western blotting were used to detect the mRNA and protein levels of Notch1 homolog (Notch1), Delta-like ligand 4 (Dll4), Delta-like ligand 4 (VEGF), and angiopoietin 2 (Ang-2), respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group, the epidermis exhibited excessive keratinization, vacuolar cytoplasm, and a large number of inflammatory cells infiltrating the tissue, while in the XZM group, a large amount of scab formation was observed in the epidermis, with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group, partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group, the MVD in the wound tissue increased in the model group, as well as the mRNA expression and protein levels of Notch1 and Dll4, while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased (P<0.05 or P<0.01). Compared to those in the model group, the MVD in the wound tissue of all medication groups significantly increased, and the mRNA and protein levels of Notch1 and Dll4 decreased, while VEGFA and Ang-2 mRNA expression and protein levels increased (P<0.05 or P<0.01). Compared to the XZM group, the inhibitor group and the combination group showed decreased MVD in wound tissue, increased Notch1 and Dll4 mRNA and protein levels, and decreased expression of VEGFA and Ang-2 mRNA and proteins (P<0.05 or P<0.01). ConclusionXZM can effectively promote wound healing in DFU rats, and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue, therey promoting angiogenesis.
2.Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.
Yue ZHANG ; Jingwen GAO ; Na LI ; Peng XU ; Shimeng QU ; Jinqian CHENG ; Mingrui WANG ; Xueru LI ; Yaheng SONG ; Fan XIAO ; Xinyu YANG ; Jihong LIU ; Hao HONG ; Ronghao MU ; Xiaotian LI ; Youmei WANG ; Hui XU ; Yuan XIE ; Tianming GAO ; Guangji WANG ; Jiye AA
Acta Pharmaceutica Sinica B 2024;14(2):667-681
Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.
3.Clinical Characteristics and Potential Risk Factors Analysis of Liver Injury Related to Epimedii Folium Preparation
Yongkang ZHAO ; Yuyang LIU ; Wei SHI ; Han GAO ; Zheng LI ; Zhaofang BAI ; Haibo SONG ; Yuan GAO ; Jiabo WANG ; Xiaohe XIAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):205-210
ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation (EP) and explore the possible risk factors of liver injury, so as to provide a reference for the safe clinical application of Epimedii Folium (EF). MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend, indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men, with an onset age range of 15-91 years old and a median onset age of 60 years old (median onset ages for men and women are 59 and 60 years old, respectively). The time span from taking EP alone to the occurrence of liver injury is 1-386 days, with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days, with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney, indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors, it is found that patients have unreasonable medication methods such as excessive dosage, repeated use, and multi-drug combination, which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP, and in clinical use, it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.
4.Research progress in the immune escape mechanism of Trichinella spiralis
Yan-Hong QIAN ; Shuai SONG ; Xiao-Hui WEN ; Chun-Ling JIA ; Dian-Hong LYU ; Zi-Guo YUAN ; Sheng-Jun LUO
Chinese Journal of Zoonoses 2024;40(1):70-75
Trichinosis is a global food-borne zoonotic parasitic disease caused by Trichinella spiralis(T.spiralis),which causes serious harm to animal production,and the public health safety of humans and animals.T.spiralis has a complex devel-opment history,and its entire life cycle is completed in the same host.To coexist with the host,it has evolved various immune escape mechanisms for avoiding immune clearance by the host,thus establishing long-term chronic infection.In this study,to aid in understanding the pathogenic mechanism of T.spiralis,the immune escape mechanism of Trichinella is discussed from three aspects:the molecular role of antigens in various stages,the immune regulatory effect on the host,and the formation of cysts to generate immune isolation.
5.Prognostic risk factor analysis and prognosis prediction model construction for patients with small bowel adenocarcinoma based on the SEER database
Weiye YUAN ; Xianhao XIAO ; He SONG
Journal of China Medical University 2024;53(1):51-59
Objective To explore the risk factors affecting the prognosis of patients with small bowel adenocarcinoma(SBA),construct the SBA survival risk model,and evaluate the clinical predictive value.Methods Clinical information and prognosis data of 2 639 patients included in the surveillance,epidemiology,and end results(SEER)database were retrospectively analyzed.Overall survival(OS)and disease specific survival(DSS)were used as prognostic indicators.The training group and validation group were randomized at a 7 ∶ 3 ratio using univariate and multivariate Cox regression analysis.Prognostic factors affecting SBA sur-vival were screened,and a prognostic prediction model was constructed.The receiver operation characteristic curve,model valida-tion by validation group,and clinical decision curve.Results Age(P<0.01),tumor site(P = 0.018),size(P = 0.042),T stage(P<0.01),detection rate of positive lymph nodes(P<0.01),single tumor focus(P<0.01),and secondary liver metastasis(P<0.01)were independent risk factors affecting prognosis of OS in patients with SBA;age(P<0.01),tumor size(P= 0.022),T stage(P<0.01),detec-tion rate of positive lymph nodes(P<0.01),single tumor focus(P<0.01),and secondary liver metastasis(P<0.01)were independent risk factors affecting the prognosis of DSS in patients with SBA.The nomogram,survival risk assessment model,and calibration prediction curve were consistent with the actual curve.Conclusion Age,tumor size,T stage,detection rate of positive lymph nodes,single tumor focus,and secondary liver metastasis were independent risk factors for OS and DSS in patients with SBA.Tumor site was also an inde-pendent risk factor for OS in SBA patients.The established prognostic prediction model has good predictive value,can effectively evaluate the prognosis of SBA patients,and can provide reasonable treatment advice for patients.
6.Investigation and analysis of the current status of transjugular intrahepatic portosystemic shunt treatment for portal hypertension in China
Haozhuo GUO ; Meng NIU ; Haibo SHAO ; Xinwei HAN ; Jianbo ZHAO ; Junhui SUN ; Zhuting FANG ; Bin XIONG ; Xiaoli ZHU ; Weixin REN ; Min YUAN ; Shiping YU ; Weifu LYU ; Xueqiang ZHANG ; Chunqing ZHANG ; Lei LI ; Xuefeng LUO ; Yusheng SONG ; Yilong MA ; Tong DANG ; Hua XIANG ; Yun JIN ; Hui XUE ; Guiyun JIN ; Xiao LI ; Jiarui LI ; Shi ZHOU ; Changlu YU ; Song HE ; Lei YU ; Hongmei ZU ; Jun MA ; Yanming LEI ; Ke XU ; Xiaolong QI
Chinese Journal of Radiology 2024;58(4):437-443
Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.
7.Salidroside Ameliorates Lung Injury Induced by PM2.5 by Regulating SIRT1-PGC-1α in Mice
Hong Xiao LI ; Mei Yu LIU ; Hui SHAN ; Feng Jin TAN ; Jian ZHOU ; Jin Yuan SONG ; Qi Si LI ; Chen LIU ; Qun Dong XU ; Li YU ; Wei Wan LI
Biomedical and Environmental Sciences 2024;37(4):367-376
Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM2.5 group,SAL+PM2.5 group.On the first day,SAL was given by gavage,and on the second day,PM2.5 suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results Exposure to PM2.5 leads to obvious morphological and pathologica changes in the lung of mice.PM2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM2.5 by activating the SIRT1-PGC-1α pathway. Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.
8.Clinical Observation on the Thumb-tack Needling for Subcutaeous Embedding Combined with Joint Mobilization in the Treatment of Post-stroke Shoulder-Hand Syndrome
Jing-Xia CHEN ; Xiao-Han YUAN ; Hong-Xing LIU ; Bo-Wen LI ; Mei-Yu JIANG ; Ya-Nan ZHAO ; Wen-Feng SONG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):689-695
Objective To observe the clinical efficacy of thumb-tack needling for subcutaeous embedding combined with joint mobilization in the treatment of post-stroke shoulder-hand syndrome.Methods A total of 80 patients with post-stroke shoulder-hand syndrome were randomly divided into a treatment group and a control group,with 40 patients in each group.Both groups were given arthrocentesis,the control group was given ordinary acupuncture on the basis of arthrocentesis,and the treatment group was combined with thumb-tack needling for subcutaeous embedding.One course of treatment was 4 weeks and a total of 4 weeks of treatment was given.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes of Visual Analogue Scale(VAS)of pain scores and simplified Fugl-Meyer Assessment(FMA)scores,as well as the pain-free passive forward flexion and abduction of the shoulder joint of the affected limb were observed before and after treatment.The Simple Quality of Life Scale(SF-36)scores of the patients in the two groups were compared after treatment.The safety and the occurrence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate was 95.00%(38/40)in the treatment group and 80.00%(32/40)in the control group.The efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,the VAS scores and upper extremity FMA scores of the patients in the two groups were significantly improved(P<0.05),and the treatment group was significantly superior to the control group in improving the VAS scores and upper extremity FMA scores,and the differences were statistically significant(P<0.05).(3)After treatment,the joint mobility of patients in the two groups were significantly improved(P<0.05),and the improvement of shoulder joint movement in the treatment group was superior to that in the control group,and the difference was statistically significant(P<0.05).(4)After treatment,the SF-36 Quality of Life Scale scores of the treatment group were significantly superior to those of the control group in terms of physical function,psychological function,emotional health,and social function levels,and the difference was statistically significant(P<0.05).(5)There was no significant difference in the incidence of adverse reactions between the treatment group and the control group(P>0.05).Conclusion Thumb-tack needling for subcutaeous embedding combined with joint mobilization exert certain effect in the treatment of post-stroke shoulder-hand syndrome.It can significantly improve the pain symptoms of patients,thus improving their quality of life,and the clinical effect is remarkable.
9.Value of contrast-enhanced ultrasonography in microwave ablation treatment of symptomatic focal uterine adenomyosis
Xiao-Long LI ; Jia-Xin LI ; Song-Yuan YU ; Pei-Li FAN ; Yun-Jie JIN ; Er-Jiao XU ; Sai-Nan GUAN ; Er-Ya DENG ; Qiu-Yan LI ; Zheng-Biao JI ; Jiu-Ling QI ; Hui-Xiong XU ;
Ultrasonography 2024;43(1):68-77
Purpose:
This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis.
Methods:
This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up.
Results:
No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered.
Conclusion
CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.
10.A multicenter population investigation on precancerous lesions of gastric cancer in Lishui District,Nan-jing
Chunyan NIU ; Xiaoping WANG ; Xiangyang ZHAO ; Jiankang HUANG ; Yue CHEN ; Yongqiang SHI ; Yongqiang SONG ; Hui WANG ; Xinguo WU ; Yongdan BU ; Jijin LI ; Tao TAO ; Jinhua WU ; Changlin XUE ; Fuyu ZHANG ; Jinming YANG ; Chunrong HAN ; Juan YUAN ; Yinling WU ; Hongbing XIONG ; Peng XIAO
The Journal of Practical Medicine 2024;40(20):2929-2934
Objective By population survey,to explore the epidemiological characteristics of gastric precancerous lesions in Lishui District of Nanjing and provide objective basis for the prevention and treatment of early gastric cancer.Methods From July 2021 to December 2022,21 977 patients who received endoscopy and/or 13C-UBT in Lishui District People's Hospital and 6 medical community units in Nanjing City were retrospectively analyzed for demography characteristics,detection rate of gastric precancerous lesions,and H.Pylori infection rate.Results(1)590 cases of gastric precancerous lesions were detected(detection rate 2.68%);(2)The total detection rate of precancerous lesions and three pathological types in males were all higher than those in females(all P<0.001);(3)The minimum age for the total detection rate of precancerous lesions in males and the mini-mum age for each pathological type were lower than in females(P<0.001,0.009,0.005,0.002);(4)The popu-lation total H.pylori infection rate was 23.10%,the H.pylori infection rate in patients with precancerous lesions was higher than that in non-precancerous lesions(P<0.001),both H.pylori infection rate of male and female in precancerous lesions were all higher than those of non-precancerous lesions of the same sex(all P<0.001),in addition,the H.pylori infection rate of male whether in precancerous or non-precancerous lesions was higher than that of female(all P<0.001);(5)The precancerous lesions detection rate in male,female,and the overall age range of 20~29 to 70~79 years is positively correlated with age growth(P<0.001),and rapidly decreases after the age of 79,the of H.pylori infection rate was also positively correlated with age growth(P<0.001),and the trend of age change(P<0.001)was parallel to the precancerous lesions detection rate.Conclusions The detec-tion rate of gastric precancerous lesions in this region is above the average level in China;the total H.pylori infec-tion rate is at a relatively low level in China;the H.pylori infection rate is parallel to the age trend of the detection rate of gastric precancerous lesions,and increases with age.

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