1.Olfactory mucosal mesenchymal stem cells inhibit ferroptosis and attenuate cerebral ischemia-reperfusion injury by up-regulating GPX4
Junhong ZHUANG ; Guoshuai YANG ; Jun PENG ; Zigui CHEN ; Hong TANG ; Ying XIA
Journal of Army Medical University 2025;47(13):1420-1428
Objective To investigate whether olfactory mucosa mesenchymal stem cells(OM-MSCs)attenuate oxygen glucose deprivation and recovery(OGD/R)-induced ferroptosis in neurons through glutathione oxidase 4(GPX4).Methods The middle nasal tissue were collected from a patient with nasal polyps admitted in our hospital,and then OM-MSCs were isolated from the tissue,which were confirmed by morphological observation under light microscopy and phenotypic characterization through flow cytometry for surface markers,including CD34,CD45,CD73,CD90,CD105,and CD146.Mouse hippocampal neuronal cell line HT22 was randomly divided into control,Control,OGD/R,OGD/R+OM-MSCs,OGD/R+sh-NC,OGD/R+sh-GPX4 and OGD/R+sh-GPX4+OM-MSCs groups.After the cells were subjected to OGD/R modeling,the cells were subsequently co-cultured with OM-MSCs and/or knockdown of GPX4.Neuronal apoptosis was quantified by flow cytometry,while cell viability was assessed using CCK-8 assay.Biochemical markers associated with ferroptosis,including MDA,ROS,GSH,and Fe2? levels,were measured with corresponding reagent kits.The GPX4 expression at both mRNA and protein levels was determined through qPCR and Western blotting,respectively.Results The isolated and primarily cultured OM-MSCs showed typical characteristics of OM-MSCs in cell surface markers(negative expression of CD34 and CD45 but positive expression of CD73,CD90,CD105,and CD146 on cell surface)and morphology(adherent cells in a spindle-like shape).Significant differences were observed among the control,OGD/R,and OGD/R+OM-MSCs groups in terms of cell viability,MDA,ROS,GSH,Fe2+and GPX4(P<0.05).The OGD/R group showed notable decreases in cell activity and GSH(P<0.05),increases in MDA,ROS,and Fe2+(P<0.05),and down-regulation of GPX4 when compared with the control group(P<005).Co-culture with OM-MSCs enhanced cell activity and GSH(P<0.05),decreased MDA,ROS,and Fe2+(P<0.05),and up-regulated GPX4 as compared to the conditions in the OGD/R group(P<0.05).While,OGD/R+sh-GPX4 treament developed the decreases in cell viability,GSH,and GPX4 and the increases in MDA,ROS,and Fe2+as compared to the OGD/R+sh-NC group(P<0.05),however,all of these could be reversed by OM-MSCs.Conclusion OM-MSCs inhibit OGD/R-induced ferroptosis in HT22 cells by up-regulating GPX4.
2.Clinicopathologic features with pulmonary and tracheal glomus tumor: report of 8 cases
Jinxing ZHOU ; Ping MA ; Meiling BAO ; Jinling TANG ; Zigui ZOU ; Hongxia LI
Chinese Journal of Oncology 2025;47(4):349-355
Objective:To study the clinical and pathological features, immunophenotypes, molecular genetics characteristics, differential diagnosis, and prognostic factors of pulmonary and tracheal glomus tumors.Method:Eight cases of pulmonary and tracheal glomus tumors were collected in Jiangsu Provincial Hospital (including 1 consultation, from Gaochun People's Hospital, Nanjing, China) between May 2015 and April 2023, and their clinical and imaging data, pathological morphology, and immunohistochemical characteristics were retrospectively analyzed. Gene testing and follow-up were performed.Result:There were 5 males and 3 females with onset ages ranging from 29 to 75 years old, median age 63.5 years. Among the patients, 5 cases were located in the trachea and 3 cases in the lungs. Under light microscopy, 5 cases were benign glomus tumors with clear boundaries, diffuse sheet or nest-like distribution, small, round or short spindle-shaped tumor cells, rounded and centered nuclei, and no obvious nuclear mitosis was seen. Two cases of glomus tumor of uncertain malignant potential showed an infiltrative growth pattern involving smooth muscle, nerves and blood vessels with necrosis and calcification, the tumor cells were more uniform in size, round or short spindle-shaped nuclei, and no obvious nuclear mitosis was seen; One case of malignant glomus tumor was seen in sarcomatous areas, lung membrane invasion and necrosis, the tumor cells were highly heterogeneous, binucleated and multinucleated, with nuclear mitoses of 20/50 high power field (HPF), and pathologic nuclear mitoses were easy to be seen. Immunohistochemically, SMA, Calponin, H-caldesmon, Vimentin and Collagen Ⅳ were all positive (8/8). Some cases expressed Syn (3/8) and Bcl-2 (4/8). The Ki-67 proliferation index was 1-2% (7/8) and 40% (1/8). BRAF V600E were detected as wild-type (8/8), and no mutations were detected in exons 2, 3, and 4 of KRAS human EML4- ALK fusion gene were negative in 5 surgical cases. Case 6 showed HMBOX1- ALK gene fusion, TERT gene mutation and CDKN2A gene deletion, and case 8 showed CARMN- NOTCH2 gene fusion. Seven cases were followed up (8-103 months, median follow-up time 30 months), 1 case was lost, 1 case recurred 21 months after surgery, and others with no evidence of recurrence or metastasis. Conclusions:Pulmonary and tracheal glomus tumors are very rare and need to be differentiated from other common tumors by combining pathological morphology and immunohistochemistry. Maybe there are some differences in the malignant diagnostic criteria and molecular genetic characteristics between visceral derived glomus tumors and soft tissue derived tumors of the same kind, such as limbs and skin. More data accumulation is needed.
3.Clinicopathologic features with pulmonary and tracheal glomus tumor: report of 8 cases
Jinxing ZHOU ; Ping MA ; Meiling BAO ; Jinling TANG ; Zigui ZOU ; Hongxia LI
Chinese Journal of Oncology 2025;47(4):349-355
Objective:To study the clinical and pathological features, immunophenotypes, molecular genetics characteristics, differential diagnosis, and prognostic factors of pulmonary and tracheal glomus tumors.Method:Eight cases of pulmonary and tracheal glomus tumors were collected in Jiangsu Provincial Hospital (including 1 consultation, from Gaochun People's Hospital, Nanjing, China) between May 2015 and April 2023, and their clinical and imaging data, pathological morphology, and immunohistochemical characteristics were retrospectively analyzed. Gene testing and follow-up were performed.Result:There were 5 males and 3 females with onset ages ranging from 29 to 75 years old, median age 63.5 years. Among the patients, 5 cases were located in the trachea and 3 cases in the lungs. Under light microscopy, 5 cases were benign glomus tumors with clear boundaries, diffuse sheet or nest-like distribution, small, round or short spindle-shaped tumor cells, rounded and centered nuclei, and no obvious nuclear mitosis was seen. Two cases of glomus tumor of uncertain malignant potential showed an infiltrative growth pattern involving smooth muscle, nerves and blood vessels with necrosis and calcification, the tumor cells were more uniform in size, round or short spindle-shaped nuclei, and no obvious nuclear mitosis was seen; One case of malignant glomus tumor was seen in sarcomatous areas, lung membrane invasion and necrosis, the tumor cells were highly heterogeneous, binucleated and multinucleated, with nuclear mitoses of 20/50 high power field (HPF), and pathologic nuclear mitoses were easy to be seen. Immunohistochemically, SMA, Calponin, H-caldesmon, Vimentin and Collagen Ⅳ were all positive (8/8). Some cases expressed Syn (3/8) and Bcl-2 (4/8). The Ki-67 proliferation index was 1-2% (7/8) and 40% (1/8). BRAF V600E were detected as wild-type (8/8), and no mutations were detected in exons 2, 3, and 4 of KRAS human EML4- ALK fusion gene were negative in 5 surgical cases. Case 6 showed HMBOX1- ALK gene fusion, TERT gene mutation and CDKN2A gene deletion, and case 8 showed CARMN- NOTCH2 gene fusion. Seven cases were followed up (8-103 months, median follow-up time 30 months), 1 case was lost, 1 case recurred 21 months after surgery, and others with no evidence of recurrence or metastasis. Conclusions:Pulmonary and tracheal glomus tumors are very rare and need to be differentiated from other common tumors by combining pathological morphology and immunohistochemistry. Maybe there are some differences in the malignant diagnostic criteria and molecular genetic characteristics between visceral derived glomus tumors and soft tissue derived tumors of the same kind, such as limbs and skin. More data accumulation is needed.
4.A Comparison Study of Combined Medication of Telmisartan with Amlodipine on the Reversal Left Ventricular Remodeling in Renal Hypertensive Rats
Xiangqin MA ; Xianfeng HUANG ; Zekai LU ; Kun ZHANG ; Zigui TANG ; Xinhui HU ; Guohui FU ; Hongmei YANG
Tianjin Medical Journal 2013;(11):1114-1116
Objective To compare the effects of telmisartan and (or) amlodipine on the reversal left ventricular re-modeling in two-kidney one clip hypertensive rats. Methods A total of 50 healthy male SD rats were randomly divided into 5 groups (n=10):two-kidney one clip renal hypertensive (2KIC) model group, sham group, telmisartan (10 mg/kg) group, am-lodipine (2.5 mg/kg) group and telmisartan (10 mg/kg)+amlodipine(2.5 mg/kg) group. The model of two-kidney one clip re-nal hypertensive rats was established. The tail arterial blood pressure was detected once a week. After 20 weeks, rats were sacrificed and specimens were collected. The left ventricular mass index (LVMI) was assessed. The myocardial ultrastructur-al changes were observed by electron microscope. Values of plasma renin activity (PRA), angiotensionⅡ(AngⅡ) and atrial natriuretic peptide (ANP) were measured by enzyme linked immunosorbent assay (ELISA).Results Compared with sham group, the levels of systolic blood pressure (SBP), LVMI, PRA, AngⅡand ANP were significantly higher in 2KIC group (P<0.01). Compared with 2KIC group, values of SBP, LVMI, PRA and ANP were significantly lower in telmisartan group and am-lodipine group (P<0.01), but the value of AngⅡwas significantly higher (P<0.01). The levels of SBP, LVMI, AngⅡand ANP were significantly lower in combined medication group than those of single drug medication group (P<0.01). There was no significant difference in the plasma PRA level between those groups (P>0.05). Results of myocardial electron microsco-py showed that the left ventricular remodeling was significantly improved in combined treatment group. Conclusion Telmisartan and amlodipine can effectively improve the left ventricular remodeling induced by hypertension. There was more effective therapy using both medications together.
5.Management of Gas Gangrene in Wenchuan Earthquake Victims
CHEN ENQIANG ; DENG LINYU ; LIU ZIGUI ; ZHU XIA ; CHEN XUEBING ; TANG HONG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(1):83-87
Gas gangrene is an emergency condition,which usually develops after injuries or surgery.This study was designed to investigate clinical characteristics,appropriate therapy,and effective control of nosocomial cross-infection of gas gangrene in Wenchuan earthquake victims.Data on diagnosis,treatment,and prevention of confirmed,suspected,or highly suspected gas gangrene were collected.Sixty-seven (2.41%) cases of suspected gas gangrene were found,in which 32 cases were highly suspected of gas gangrene and 5 cases were confirmed by culture of Clostridium perfringens.Thereof,injury sites were mainly located on the limbs,and typical indications,including crepitation,severe localized pain,swelling,wound discoloration,dark red or black necrotic muscle,foul smell as well as different degrees of systemic toxic performance were common among them.After hospitalization,all patients were isolated and had surgery quickly to remove dead,damaged or infected tissue.The wounds were also exposed for drainage and washed or padded with 3% liquid hydrogen peroxide for disinfection before all diagnostic test results were available.Additionally,high doses of antibiotics (mainly penicillin) were given for the prevention of infection,and supportive therapy was applied for corresponding symptoms control.Among those cases,no fatality was reported.In summary,in post-disaster emergency relief,the diagnosis of gas gangrene should be primarily based on clinical manifestations; while patient isolation,wound debridement and disinfection,as well as antibiotics treatment,is the main measures for proper treatment and control of nosocomial infection for gas gangrene.
6.Management of gas gangrene in Wenchuan earthquake victims.
Enqiang, CHEN ; Linyu, DENG ; Zigui, LIU ; Xia, ZHU ; Xuebing, CHEN ; Hong, TANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(1):83-7
Gas gangrene is an emergency condition, which usually develops after injuries or surgery. This study was designed to investigate clinical characteristics, appropriate therapy, and effective control of nosocomial cross-infection of gas gangrene in Wenchuan earthquake victims. Data on diagnosis, treatment, and prevention of confirmed, suspected, or highly suspected gas gangrene were collected. Sixty-seven (2.41%) cases of suspected gas gangrene were found, in which 32 cases were highly suspected of gas gangrene and 5 cases were confirmed by culture of Clostridium perfringens. Thereof, injury sites were mainly located on the limbs, and typical indications, including crepitation, severe localized pain, swelling, wound discoloration, dark red or black necrotic muscle, foul smell as well as different degrees of systemic toxic performance were common among them. After hospitalization, all patients were isolated and had surgery quickly to remove dead, damaged or infected tissue. The wounds were also exposed for drainage and washed or padded with 3% liquid hydrogen peroxide for disinfection before all diagnostic test results were available. Additionally, high doses of antibiotics (mainly penicillin) were given for the prevention of infection, and supportive therapy was applied for corresponding symptoms control. Among those cases, no fatality was reported. In summary, in post-disaster emergency relief, the diagnosis of gas gangrene should be primarily based on clinical manifestations; while patient isolation, wound debridement and disinfection, as well as antibiotics treatment, is the main measures for proper treatment and control of nosocomial infection for gas gangrene.

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