1.Deubiquitinase JOSD2 alleviates colitis by inhibiting inflammation via deubiquitination of IMPDH2 in macrophages.
Xin LIU ; Yi FANG ; Mincong HUANG ; Shiliang TU ; Boan ZHENG ; Hang YUAN ; Peng YU ; Mengyao LAN ; Wu LUO ; Yongqiang ZHOU ; Guorong CHEN ; Zhe SHEN ; Yi WANG ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(2):1039-1055
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.
2.Microwave ablation synchronously with biopsy strategy for pulmonary nodules
Chengzhi ZHANG ; Zhanguo SUN ; Yi FANG ; Mengyao SONG ; Xinwei HAN ; Dechao JIAO
Journal of Practical Radiology 2024;40(4):637-640
Objective To evaluate the efficacy of microwave ablation(MWA)synchronously with biopsy for pulmonary nodules.Methods The data of 64 patients with MWA combined with biopsy were analyzed retrospectively.Thirty-one patients(non-synchronous group)were treated with ablation following biopsy in turn to identify malignant tumors,and 33 patients(synchronous group)were treated by ablation and biopsy synchronously.The technical success rate,operation time,complications,hospitalization time and expenses were compared between non-synchronous group and synchronous group.Results The technical success rate,pneumothorax,and pleural effusion rate showed no significance between the two groups(P>0.05).There were all significant differences in operation time(42.00 min vs 54.26 min),hospitalization time(5.09 days vs 9.26 days),hospitalization expenses(26 840.61 yuan vs 32 527.26 yuan),lung hemorrhage(27.27%vs 87.10%)and hemoptysis(3.03%vs 19.35%)between synchronous group and non-synchronous group,respectively(P<0.05).Conclusion MWA synchronously with biopsy for pulmonary nodules is safe and feasible,which can reduce intraoperative bleeding,shorten treatment period and reduce hospitalization expenses.
3.Role of TRPV1 in Cardiovascular Disease and the Related Progress of Traditional Chinese Medicine Research
Hongying LYU ; Mingshuang HOU ; Guanjun JIA ; Yushun KOU ; Mengyao LI ; Yongxiang LI ; Jing XU ; Qianqian CHEN ; Zhengjie TENG ; Lin YI
Chinese Journal of Modern Applied Pharmacy 2024;41(4):556-566
Transient receptor potential vanilloid-1(TRPV1) channel is a non-selective ligand-gated cationic channel with multiple activation mechanisms in the transient receptor potential subfamily. In recent years, a large number of studies have found that TRPV1 plays an important role in the field of cardiovascular diseases such as hypertension and atherosclerosis. With the in-depth study of traditional Chinese medicine, it has been found that Chinese medicine monomers and their active components can activate or inhibit TRPV1 channels, which has certain potential in the study of cardiovascular diseases. In this paper, the role of TRPV1 channel in cardiovascular diseases and the research progress of traditional Chinese medicine prevention and treatment of cardiovascular diseases based on TRPV1 channel are reviewed, in order to provide new ideas for prevention and treatment of cardiovascular system diseases.
4.The effect of glycopyrrolate on intestinal spasm and hemodynamics in painless colonoscopy
Yan ZHANG ; Mengyao YI ; Changfeng FANG ; Le ZHANG ; Jie ZHENG ; Yuanxiao LU ; Qi YE ; Zhijian YE ; Tao FANG
Chinese Journal of Internal Medicine 2024;63(6):600-604
Objective:To investigate the effects of glycopyrrolate on intestinal spasm and hemodynamics in painless colonoscopy.Methods:A total of 100 patients who were scheduled to undergo painless colonoscopy were selected as the study subjects and randomly divided into two groups by a computerized number method. Ten patients in both groups dropped out because of disruption of the study protocol, and 45 patients from each group were included in the final analysis. Before anesthesia induction, patients in group glycopyrrolate (group G) were injected with 0.2 mg glycopyrrolate, while those in congtrol group (group C) were injected with an equal amount of saline. The heart rate, systolic blood pressure, and diastolic blood pressure were recorded at T 0 (baseline period), T 1 (after anesthesia induction), T 2 (colonoscopy over sigmoid colon), T 3 (colonoscopy over the liver region), T 4 (after the end of examination), and T 5 (at the awakening phase), and the degree of intestinal spasm was assessed intraoperatively using the Likert′s four-point scale. The numerical rating scale (NRS) was used to assess preoperative and postoperative pain. The incidence of adverse events was recorded. Results:The general data at baseline were not statistically different between the two groups ( P>0.05). During the procedure, patients in group G had lower intraoperative intestinal spasm scores than those in group C ( P=0.028). Intraoperative hypotension and bradycardia occurrence were lower in group G than in group C ( P<0.05), and intraoperative norepinephrine use was also lower than in the group C ( P=0.034). Postoperative visual analog scale pain scores were lower in group G ( P=0.047), but patients who used glycopyrrolate had a higher proportion of dry mouth ( P=0.035). Conclusion:During painless colonoscopy, preoperative administration of glycopyrrolate significantly improved intraoperative hemodynamic fluctuations, reduced the incidence of hypotension and bradycardia, and relieved postoperative pain. However, glycopyrrolate use resulted in the risk of dry mouth.
5.Trans-sheath intraluminal forceps biopsy under digital subtraction angiography guidance for assisting diagnosis of pulmonary artery obstructive diseases
Rongna HOU ; Xueliang ZHOU ; Mengyao SONG ; Chengzhi ZHANG ; Zhanguo SUN ; Yi FANG ; Xinwei HAN ; Dechao JIAO
Chinese Journal of Interventional Imaging and Therapy 2024;21(7):390-392
Objective To explore the efficiency and safety of trans-sheath intraluminal forceps biopsy under digital subtraction angiography(DSA)guidance for assisting diagnosis of pulmonary artery obstructive diseases.Methods Data of 16 patients who underwent trans-sheath intraluminal forceps biopsy for pulmonary artery obstructive diseases were retrospectively analyzed,and the clinical manifestations were recorded.The technical success of biopsy was defined as tissue obtained met the needs of pathology diagnosis.For patients with malignant pathology results,the final diagnosis was malignant,for those with benign pathology results after biopsy and no obvious changes after 6-month or longer follow-up,or benign pathology results after surgical resection,the final diagnosis was benign,otherwise was no clear diagnosis.The operation time,technical success rate,diagnostic efficiency,complications and changes of pulmonary artery pressure before and after the biopsy were observed.Results Among 16 patients,9 complained of intermittent chest tightness,4 complained of chest pain with chest tightness,2 complained of chest pain but 1 denied any symptoms.The lesions located in the left lung in 10 cases and in the right lung in 6 cases,all with enhanced CT showed filling defects of the involved branch of pulmonary artery.Totally 16 trans-sheath intraluminal forceps biopsies were performed in 16 patients,with an average operation time of(31.02±6.02)min and technical success rate of 100%.Malignant tumors were finally diagnosed in 10 cases,including 1 case of lung cancer with false-negative biopsy result,while biopsy correctly diagnosed benign lesions in the other 6 cases.Transient worsening chest pain with chest tightness occurred in 2 cases and relieved after symptomatic treatments.No statistically significant difference of pulmonary artery pressure was found before([53.38±14.28]mmHg)and after([53.69±14.15]mmHg)biopsy(P>0.05).Conclusion DSA-guided trans-sheath intraluminal forceps biopsy was relatively safe and valuable for assisting diagnosis of pulmonary artery obstructive diseases.
6.Establishment of quantitative analysis of multi-components by single marker for content determination of 10 ganoderic acids in Ganoderma lucidum
Shu LUO ; Yi SONG ; Xia LUO ; Nan JIANG ; Mengyao YU ; Xiaoyan XU
China Pharmacy 2023;34(14):1703-1706
OBJECTIVE To establish a quantitative analysis of multi-components by single marker (QAMS) method for simultaneous determination of 10 ganoderic acids in Ganoderma lucidum. METHODS Using ganoderic acid A as internal reference, high-performance liquid chromatography (HPLC) method was adopted to calculate relative correction factors of the other 9 components, such as ganoderic acid B, ganoderic acid C2, ganoderic acid D, ganoderic acid F, ganoderic acid H, ganoderenic acid A, ganoderenic acid B, ganoderenic acid C, ganoderenic acid D; the contents of above ganoderic acids were calculated with relative correction factors, and compared with the results of external standard method. RESULTS The linear relationship of ganoderic acid A, ganoderic acid B, ganoderic acid C2, ganoderic acid D, ganoderic acid F, ganoderic acid H, ganoderenic acid A, ganoderenic acid B, ganoderenic acid C and ganoderenic acid D were 0.032-3.996, 0.040-4.971, 0.037-4.568, 0.028-3.558, 0.033-4.177, 0.044-5.440, 0.032-3.944, 0.040-4.994, 0.045-5.593 and 0.035-4.342 mg/mL (all R 2≥0.999 2), respectively. RSDs of precision, stability (24 h) and reproducibility tests were all lower than 2%. Their average recovery rates were 99.43%, 100.25%, 98.50%, 99.88%, 100.59%, 99.64%, 98.50%, 99.40%, 99.64% and 99.76%, respectively (RSD<2%, n=6). Relative correction factors of ganoderic acid B, ganoderic acid C2, ganoderic acid D, ganoderic acid F, ganoderic acid H, ganoderenic acid A, ganoderenic acid B, ganoderenic acid C and ganoderenic acid D were 1.788 5, 1.288 2, 1.126 4, 1.698 5, 0.885 4, 5.468 1, 4.210 9, 5.780 8, 4.290 3, respectively. Relative errors between the content obtained by QAMS method and external standard method for G. lucidum from different origins were within ±12%. CONCLUSIONS It is feasible that the contents of 10 ganoderic acids are determined simultaneously by QAMS method, using ganoderic acid A as internal reference. This method shows good precision and reproducibility and can be used for the quality control of G. lucidum.
7.Effect of the comprehensive intervention measures on Yunnan unexplained sudden death in Dali Prefecture
Xue TANG ; Yanmei XI ; Lin MA ; Mengyao SUN ; Yongpeng YANG ; Yi DONG ; Mingfang QIN ; Yuebing WANG
Chinese Journal of Endemiology 2023;42(1):41-46
Objective:To evaluate the effect of comprehensive intervention measures on Yunnan unexplained sudden death (YUSD) in Dali Prefecture, Yunnan Province, and to provide scientific basis for improving the prevention and control measures.Methods:Since 2010, Yunnan Province had implemented comprehensive intervention measures in ward areas according to the etiological pattern of YUSD. In July 2019, 47 families with YUSD were selected as case families and 23 families without YUSD were selected as control families in 31 natural villages of Heqing, Xiangyun, Yunlong, Eryuan, Jianchuan, Binchuan and Nanjian counties of Dali Prefecture. A unified questionnaire was used to investigate the basic information, economic status, dietary structure, and health literacy of the families during the two periods of "the first sudden death case" and "the present".Results:The annual household income of the case families at present (median, 20 492.6 yuan) was significantly higher than that of the first sudden death case (3 883.4 yuan), and the difference was statistically significant ( Z = - 5.27, P < 0.001). At present, rice (76.6%, 36/47) was the main diet of the case families; at the time of the first sudden death case, 23.4% (11/47) of the case families could not eat enough, and there was no such situation in the case families at present. Compared with the time of the first sudden death case, the dietary habits of the case families at present were as follows: the proportion of eating Trogia venenata decreased from 19.0% (39/205) to 0 (0/190), the proportion of eating wild fruit decreased from 17.1% (35/205) to 9.5% (18/190), and the proportion of drinking raw water decreased from 55.1% (113/205) to 42.1% (80/190), and the differences were statistically significant (χ 2 = 22.37, 4.90, 6.86, P < 0.05). Lifestyle and health awareness: the proportion of those who washed their hands before meals and after using the toilet increased from 9.8% (20/205) to 41.6% (79/190), those who did not overwork increased from 16.6% (34/205) to 34.2% (65/190), and those who took good protection when spraying pesticides increased from 7.3% (15/205) to 21.6% (41/190), and the differences were statistically significant (χ 2 = 53.17, 33.94, 16.48, P < 0.001). Toilet habits: the proportion of using outdoor toilet decreased from 75.6% (155/205) to 9.5% (18/190), the difference was statistically significant (χ 2 = 175.21, P < 0.001). When the first sudden death case occurred, the proportions of eating Trogia venenata and using outdoor toilet in the case families were higher than those in the control families (χ 2 = 22.37, 23.70, P < 0.001), the proportions of those who washed their hands before meals and after using the toilet and those who did not overwork in the case families were lower than those in the control families (χ 2 = 7.38, 4.93, P < 0.05). Conclusions:The economic conditions, production and living conditions of YUSD areas in Dali Prefecture have been significantly improved, and the health literacy and health prevention awareness of the population have been greatly improved. Economic conditions and living standard, dietary structure and health literacy may be related factors of YUSD.
8.Investigation and analysis of two suspected Yunnan sudden unexplained death cases in a village with a history of Yunnan sudden unexplained death
Yanmei XI ; Puping LEI ; Zhengjiang ZHANG ; Jianzhong BAO ; Yi DONG ; Lin MA ; Xue TANG ; Yongpeng YANG ; Mengyao SUN ; Zhizhong SONG ; Yuebing WANG
Chinese Journal of Endemiology 2022;41(5):389-392
Objective:To explore the cause of death of 2 suspected Yunnan sudden unexplained death (YNSUD) cases in Dayao County, Yunnan Province.Methods:The field epidemiological investigation and autopsy of 2 cases of YNSUD in Dayao County from June 15 to 20, 2020 were conducted; and blood and tissue samples were collected for qualitative analysis of common poisons and drugs.Results:The areas where the two cases were located were all seriously ill villages with a history of YNSUD, and the time of death occurred in the onset season of YNSUD. There was no blood relationship between the 2 cases, no obvious abnormal symptoms before death, no special diet, no history of exposure to pesticides and other toxic chemicals, and the test results of common poisons were all negative. Autopsy pathological examination results showed that case 1 died of acute cardiac dysfunction caused by sudden acute myocardial infarction of coronary heart disease, and case 2 died of central respiratory and circulatory failure caused by spontaneous subarachnoid hemorrhage.Conclusions:The two cases are excluded from YNSUD through autopsy, and the cause of death is determined. It is suggested that emergency response should be taken as soon as possible for YNSUD cases, and autopsy should be actively carried out to clarify the cause of death from a pathological point of view.
9.Genetic analysis of a weak D type61 sample from a blood donor, Jiangyin
Fang WANG ; Mengyao BIAN ; Qiurong YU ; Minglei WU ; Haiping ZHAO ; Ling SUN ; Buqiang WANG ; Hongjun GAO ; Haicai SHI ; Yi WU ; Ming GAO ; Yuping CHEN
Chinese Journal of Blood Transfusion 2022;35(7):701-704
【Objective】 To genetically analyze the Del sample from a blood donor in Jiangyin and make clear the molecular basis of the serological phenotype. 【Methods】 The EDTA anticoagulant blood were collected: buffy coat were used for nucleic acid extract and cDNA analysis; red blood cells for serological test. Tube method and microcolumn gel were used for serological test. Genotyping kit were used for exon analysis. Gene mutation was analyzed using the sequence analyzer. 【Results】 Serological analysis demonstrated the sample′s RhD phenotype was Del. The phenotype of RhCE was CCEe. Real-time fluorescence quota PCR result demonstrated the existence of all exones. Weak D15 and RHD* DEL1 [RHD(1227G>A)], which had a high frequency of occurrence in China, were excluded according to real-time fluorescence quota PCR result. Sequence analyzing result verified RHD(28C>T) SNP mutation in cDNA. The genotype of this sample was RHD*01 W. 61[RHD(28C>T)]. 【Conclusion】 A weak D61 was found among blood donors in our city, Jiangyin.
10.Screening of ARVC desmosomal protein gene mutation in people from Yunnan unexplained sudden death area in Xiangyun County, Dali Prefecture, Yunnan Province
Lin MA ; Yuebing WANG ; Xue TANG ; Wenjuan LI ; Chunli DUAN ; Puping LEI ; Yanmei XI ; Mengyao SUN ; Yi DONG
Chinese Journal of Endemiology 2021;40(8):605-609
Objective:To investigate the mutation of desmosomal protein gene of arrhythmogenic right ventricular cardiomyopathy (ARVC) in people from Yunnan unexplained sudden death (YUSD) area in Xiangyun County, Dali Prefecture, Yunnan Province, and to explore the etiological relationship between the mutation of ARVC desmosomal protein gene and YUSD.Methods:The autopsy cardiac blood sample of YUSD case ( n = 1) and the peripheral venous blood samples of the same time case ( n = 1) and relatives of YUSD case ( n = 16) were collected in Xiangyun County. Blood DNA was extracted for PCR amplification and sequencing of a total of 97 exons of the ARVC desmosomal protein genes [plakophilin 2 (PKP2), junction plakoglobin (JUP), desmoplakin (DSP), desmoglein 2 (DSG2) and desmocollin 2 (DSC2)] were conducted by Sanger method. At the same time, basic information and genetic family of YUSD case, the same time case and relatives of YUSD case were investigated, and gene mutations were comprehensively analyzed. Results:The YUSD case and the same time case carried JUP, DSP and DSG2 gene mutations. Among the relatives of YUSD case, 2, 14, 16, 15 and 4 cases had mutations in PKP2, JUP, DSP, DSG2 and DSC2 genes, respectively. The YUSD case, the same time case and the relatives of YUSD case carried 6 identical mutation sites: JUP gene exon 3 c.213 T>C synonymous mutation, exon 14 c.2089 A>T missense mutation; DSP gene exon 19 c.2631 G>A synonymous mutation, exon 24 c.8472 G>C synonymous mutation; DSG2 gene exon 8 c.861 C>T synonymous mutation, and exon 15 c.3321 T>C synonymous mutation.Conclusion:In Xiangyun County, six identical mutation sites (JUP gene c.213 T>C and c.2089 A>T, DSP gene c.2631 G>A and c.8472 G>C, DSG2 gene c.861 C>T and c.3321 T>C) carried by YUSD case, the same time case and the relatives of YUSD case may be related to the incidence of some YUSD cases.


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