1.Complete androgen insensitivity syndrome with gender transition in adulthood: A case report
Meicen PU ; Dan WANG ; Meinan HE ; Xinzhao FAN ; Mengchen ZOU ; Yijuan HUANG ; Jiming LI ; Shanchao ZHAO ; Yunjun LIAO ; Yaoming XUE ; Ying CAO
Chinese Journal of Endocrinology and Metabolism 2024;40(7):602-607
Complete androgen insensitivity syndrome(CAIS) is characterized by lack of androgen response in target organs due to androgen receptor dysfunction, resulting in feminized external genitalia. Individuals with CAIS are typically advised to live as females. This article reports a patient diagnosed with CAIS and gender dysphoria in adulthood. Following the removal of a left pelvic mass, pathology indicated cryptorchidism with a concurrent Leydig cell tumor. Genetic testing revealed a deletion mutation in exon 3 of androgen receptor gene. During follow-up, the patient underwent gender reassignment, transitioning socially from female to male. This case provides new insights into gender allocation for CAIS patients.
2.Efficacy of continuous venovenous hemodiafiltration combined with hemoperfusion in the treatment of acute kidney injury and its influence on levels of serum nerve guidance factor-1 and kidney injury factor-1
Xiaoxia GAO ; Min ZHAO ; Yuying YANG ; Jiming LI
Chinese Journal of Postgraduates of Medicine 2024;47(12):1081-1085
Objective:To explore the efficacy of continuous venovenous hemodiafiltration (CVVHDF) combined with hemoperfusion in the treatment of acute kidney injury (AKI) and its influence on the levels of serum nerve guidance factor-1 (Netrin-1) and kidney injury factor-1 (Kim-1).Methods:A total of 193 patients with AKI diagnosed and treated in the First Affiliated Hospital of Xinjiang Medical University from January 2018 to January 2021 were prospectively selected and divided into the control group (96 cases) and the observation group (97 cases) according to random number table method. The control group was given conventional treatment, and the observation group was given CVVHDF combined with hemopirrigation on the basis of conventional treatment. The levels of Netrin-1, Kim-1, renal function index, critical disease score and inflammatory response index before and after treatment were compared between the two groups.Results:After 72 h of treatment, the serum levels of Netrin-1, Kim-1, creatinine and urea nitrogen in the observation group were lower than those in the control group: (5.43 ± 0.61)ng/L vs. (7.52 ± 0.83) ng/L, (0.97 ± 0.23) ng/L vs. (1.52 ± 0.29) ng/L, (97.58 ± 8.51) μmol/L vs. (109.80 ± 7.56) μmol/L, (5.72 ± 1.19) mmol/L vs. (7.40 ± 1.75) mmol/L, there were statistical differences ( P<0.05). After 72 h of treatment, the scores of acute physiology and chronic health evaluation Ⅱ and multiple organ dysfunction syndrome in the observation group were lower than those in the control group: (14.26 ± 5.62) scores vs. (16.82 ± 3.75) scores, (7.15 ± 0.86) scores vs. (8.23 ± 0.92) scores, there were statistical differences ( P<0.05). After 72 h of treatment, the levels of tumor necrosis factor-α, interleukin-6 and C-reactive protein in the observation group were lower than those in the control group: (13.26 ± 4.06) ng/L vs. (29.30 ± 5.81) ng/L, (14.56 ± 3.29) ng/L vs. (29.88 ± 5.40) ng/L, (12.06 ± 3.43) mg/L vs. (33.82 ± 4.94) mg/L, there were statistical differences ( P<0.05). Conclusions:CVVHDF combined with hemoperfusion can effectively improve the renal function of patients with AKI, reduce the levels of serum inflammatory factors, alleviate the disease and promote recovery.
3.Impact of age and menstrual status on semi-quantitative parameters of breast dynamic enhanced MRI in healthy women
Aijuan ZHANG ; Jiming CHEN ; Zhouli LI ; Lili WU ; Na YAN
Chinese Journal of Medical Imaging Technology 2024;40(9):1336-1340
Objective To observe the impact of age and menstrual status on semi-quantitative parameters of breast dynamic enhanced MRI(DCE-MRI)in healthy adult women.Methods A total of 283 adult females who underwent MR examinations due to suspected breast mass or breast discomfort but no breast tumor was detected after 1 year's clinical follow-up were retrospectively collected.Meanwhile,49 healthy adult female subjects in the menstrual period(menstruating subgroup)were prospectively recruited.All the above 332 subjects were divided into low age group(n=107),middle age group(n=114)and high age group(n=111)according to age,while into postmenopausal group(n=112)and premenopausal group(n=220,including 49 in menstruating subgroup,77 in proliferating subgroup and 94 in secreting subgroup).DCE-MRI semi-quantitative parameters,including maximum enhancement rate(ERmax)and maximum slope of increasing(Slopemax)were compared among different groups and subgroups,and the variations were observed.Results Significant differences of ERmax and Slopemax were found between high and low age groups(both P<0.05),while no significant difference of ERmax and Slopemax was found between middle and low age group,nor between middle and high age group(all P>0.05).Both ERmax and Slopemax in postmenopausal group were lower than those in premenopausal group(both P<0.05),while no significant difference of DCE-MRI semi-quantitative parameters was found among different menstrual cycle subgroups(all P>0.05).The coefficient of variance(CV)of normal breast ERmax in low,middle and high age groups was 56.20%,44.02%and 50.97%,respectively,of Slopemax was 54.74%,81.78%and 76.93%,respectively.CV of normal breast ERmax was 50.12%and 46.02%in postmenopausal and premenopausal groups,respectively,while CV of Slopemax was 72.84%and 62.04%,respectively.Among different subgroups,CV of ERmax and Slopemax in proliferative period were both the largest(61.39%,82.54%),which in menstrual period were both the smallest(33.99%,42.33%).Conclusion Semi-quantitative parameters of breast DCE-MRI were different among healthy women of different age and menstrual status,and the individual variations were large.
4.Factors of affecting survival of patients with septic shock after fluid resuscitation and the significance of NICaS in monitoring hemodynamic indicators of microcirculation
Patiguli·Muhemaiti ; Jiming LI
China Medical Equipment 2024;21(11):76-80
Objective:To explore and analyze the factors of affecting survival in patients with septic shock after fluid resuscitation,and the significance of noninvasive cardiovascular output monitoring system(NICaS)in monitoring hemodynamic indicators of microcirculation.Methods:A retrospective analysis was conducted on the clinical data of 90 patients with sepsis who admitted to the First Affiliated Hospital of Xinjiang Medical University from March 2020 to March 2022.According to whether occurred survival situation of the 28-day prognosis,these patients were divided into survival group(59 cases)and non-survival group(31 cases).General documents,hemodynamic indicators,and indicators of cardiac function were compared between the two groups,and the influence of hemodynamic indicators,score of Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ),change and prognosis of cardiac function of patients of septic shock were analyzed.Results:The APACHE Ⅱ score(19.21±1.82)of the non-survival group was significantly higher than that(15.68±2.31)of the survival group,with statistically significant difference between the two groups(t=7.947,P<0.05).There was no significant difference in heart rate(HR)between non-survival and the survival groups(P>0.05).Compared with the mean arterial pressure(MAP),systemic vascular resistance index(SVRI)and cardiac index(CI)of survival group,the MAP and CI of non-survival group were lower,and the SVRI of non-survival group was higher,and the differences of them between two groups were significant(t=4.887,5.398,7.057,P<0.05),respectively.There were no significant differences in left ventricular ejection fraction(LVEF),left atrial diameter(LAD),left ventricular posterior wall thickness(LVPWd),interventricular septal thickness(IVSd),E-peak velocity(E),A-peak velocity(A),and E/A ratio between non-survival group and survival groups(P>0.05).However,the LVEDD value of non-survival group was significantly higher than that of survival group,and the difference of that between two groups was statistically significant(t=9.887,P<0.05).The 28-day prognoses of patients with septic shock were used as dependent variable,and the hemodynamic indicators and cardiac indicators at the 7th day after admitted to hospital were used as independent variables,and the APACHE Ⅱ score,MAP,SVRI,CI and LVEDD with significant difference in multifactor analysis were included in logistic regression analysis equation.The results showed that APACHE Ⅱ score,CI and LVEDD could be used as high-risk independent factors that affected the prognosis of patients with septic shock(OR=1.674,0.902,1.225,P<0.05),respectively.Conclusion:APACHE Ⅱ score,CI and LVEDD can be used as high-risk independent factors that affect the prognosis of patients with septic shock.The effect will be bigger on prognosis when patients with septic shock occurred dysfunctions of cardiac contraction and relaxation at the same time.The application of NICaS monitoring system can effectively reflect the changes of hemodynamic indicators of microcirculation of the body.
5.The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"
Wanjie YANG ; Xianduo LIU ; Ximo WANG ; Weiguo XU ; Lei ZHANG ; Qiang FU ; Jiming YANG ; Jing QIAN ; Fuyu ZHANG ; Li TIAN ; Wenlong ZHANG ; Yu ZHANG ; Zheng CHEN ; Shifeng SHAO ; Xiang WANG ; Li GENG ; Yi REN ; Ying WANG ; Lixia SHI ; Zhen WAN ; Yi XIE ; Yuanyuan LIU ; Weili YU ; Jing HAN ; Li LIU ; Huan ZHU ; Zijiang YU ; Hongyang LIU ; Shimei WANG
Chinese Critical Care Medicine 2024;36(2):195-201
The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
6.MIF inhibitor ISO-1 alleviates sepsis-induced acute kidney injury by suppressing oxidative stress, inflammation, and apoptosis
Fukang Yin ; Xiaoxia Zhang ; Xiaojun Yang ; Jiming Li
Acta Universitatis Medicinalis Anhui 2024;59(12):2079-2086
Objective:
To investigate the effects and underlying mechanisms of the macrophage migration inhibitory factor(MIF) inhibitor(S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester(ISO-1) on sepsis-induced acute kidney injury(AKI).
Methods:
Human renal tubular epithelial HK-2 cells were divided into Con group(without any treatment), ISO-1 group(10 μg/ml ISO-1 treatment for 24 h) and LPS group(10 μg/ml LPS treatment for 24 h), LPS+ISO-1 group(10 μg/ml LPS treatment for 24 h followed by 10 μg/ml ISO-1 treatment for 24 h). ELISA was used to measure the levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) in the cell supernatants. Reactive oxygen species(ROS) levels were assessed using the 6-carboxyl-2 ′,7′-dichlorodihydrofluorescein diacetate fluorescent indicator(DCFH-DA) method. Apoptosis levels were detected by TUNEL staining, and Western blot was employed to analyze the expression of proteins of Kelch like ECH associated protein 1(Keap1), NFE2 like bZIP transcription factor 2(Nrf2), heme oxygenase-1(HO-1), as well as apoptosis-related proteins Bcl-2, Bax, and cleaved Caspase-3(c-Caspase-3). A sepsis mouse model was established using the cecal ligation and puncture(CLP) method, and the mice were divided into four groups: sham-operated(Sham), ISO-1 control(ISO-1), CLP, and ISO-1 treatment(CLP+ISO-1). After the experiment, mouse kidney tissues were collected for HE staining to observe pathological changes. Blood urea nitrogen(BUN), serum creatinine(Scr), myeloperoxidase(MPO) levels in kidney tissues, glutathione(GSH) and superoxide dismutase(SOD) activities were measured. Western blot was also used to detect the expression of MIF and proteins in the Nrf2/Keap1 signaling pathway and apoptosis-related proteins in kidney tissues.
Results:
Compared to the Con group, the LPS and LPS+ISO-1 groups showed significantly increased levels of TNF-α, IL-1β, IL-6, TUNEL-positive rates, ROS levels, and protein expressions of Keap1, Bax, and c-Caspase-3 in HK-2 cells(P<0.05), while the expressions of Nrf2, HO-1, and Bcl-2 significantly decreased(P<0.05). The ISO-1 group showed no significant changes(P>0.05). Compared to the LPS group, the LPS+ISO-1 group exhibited significantly decreased levels of TNF-α, IL-1β, IL-6, TUNEL-positive rates, ROS levels, and protein expressions of Keap1, Bax, and c-Caspase-3, while the expressions of Nrf2, HO-1, and Bcl-2 significantly increased(P<0.05). In the mouse experiments, compared to the Sham group, the CLP and CLP+ISO-1 groups showed severe kidney tissue damage, increased levels of serum BUN, Scr, and kidney MIF, Keap1, Bax, and c-Caspase-3 protein expressions(P<0.05), while GSH, SOD activities, and protein expressions of Nrf2, HO-1, and Bcl-2 significantly decreased(P<0.05). The ISO-1 group showed no significant changes(P>0.05). Compared to the CLP group, the CLP+ISO-1 group showed significant improvements in the aforementioned indicators(P<0.05).
Conclusion
The specific MIF inhibitor ISO-1 can ameliorate sepsis-induced AKI by inhibiting oxidative stress, inflammatory response, and apoptosis bothin vitroandin vivo. The mechanism may be through Nrf2/Keap1 signaling pathway.
7.Study on the Correlation between Changes in Serum Glycerophospholipid Metabolites LPC18∶3 and LPE 16∶1 Levels and Their Clinical Prognosis in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Jiming JIN ; Yanjie WU ; Shilin YAN ; Zhanzeng LI ; Yang LIU
Journal of Modern Laboratory Medicine 2024;39(4):93-99
Objective To explore the expression levels of serum glycerophospholipid metabolites lysophosphatidylcholine(LPC)18∶3 and lysophosphatidylethanolamine(LPE)16∶1 in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and their correlation with clinical prognosis.Methods A total of 112 AECOPD patients diagnosed and treated in Tangshan People's Hospital from January 2019 to January 2022 were selected as the AECOPD group.According to the 3-month follow-up prognosis of the AECOPD group patients,they were divided into survival group(n=90)and death group(n=22).During the same period,60 stable COPD patients were selected as the stable period group,while 60 healthy individuals in the same period were selected as the control group.High performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)was used to detect serum LPC18∶3 and LPE16∶1 levels in each group.Pearson method was used to analyze their correlation.Logistic regression analysis was used to analyze factors affecting the prognosis of AECOPD patients.Receiver operating characteristic curve was drawn to evaluate the prognostic value of LPC18∶3 and LPE16∶1 in AECOPD patients.The prognosis of AECOPD patients with different serum LPC18∶3 and LPE16∶1 expression groups was compared by K-M curve.Results Serum LPC18∶3(21.67±4.35 μ mol/L),LPE16∶1(16.20±5.17 μ mol/L),PEF%pred,FEV1%pred,and FEV1/FVC%in AECOPD group were lower than those of stable phase group(43.24±6.17 μ mol/L,32.19±5.98 μmol/L)and the control group(68.14±8.78 μ mol/L,44.82±7.44 μ mol/L),with significant differences(F=461.240~1 102.534,all P<0.05).The serum LPC18:3 and LPE16:1 levels in the AECOPD group were positively correlated with lung function indicators such as PEF%pred,FEV1%pred,and FEV1/FVC%(r=0.603~0.756,allP<0.05).The course of COPD and PCT of AECOPD patients in the death group were higher than those in the survival group(t=3.961,2.509),while the PEF%pred,FEV1%pred,FEV1/FVC%,serum LPC18∶3(17.20±4.11μ mol/L),and LPE16∶1(10.15±3.03 μ mol/L)in the death group were lower than those in the survival group(22.76±4.35 μ mol/L,17.68±5.22 μ mol/L),with significant differences(t=4.141~6.490,all P<0.05).Serum LPC18∶3(OR=0.691,95%CI:0.519~0.920)and LPE16∶1(OR=0.586,95%CI:0.382~0.901)were independent protective factors,while the course of COPD(OR=1.510,95%CI:1.203~1.895)and procalcitonin(OR=1.759,95%CI:1.159~2.671)were risk factors affecting the prognosis of AECOPD patients.The area under the curve(95%CI)of combined serum LPC18∶3 and LPE16∶1 for prognosis evaluation of AECOPD patients was better than that of serum LPC18∶3 and LPE16∶1 predicted separately[0.866(0.822~0.907)vs 0.794(0.748~0.830),0.786(0.739~0.836)](Z=3.957,4.195,P=0.002,<0.001).The mortality risk of AECOPD patients in the low expression group of LPC18∶3 and LPE16∶1 was higher than that in the high expression group of LPC18∶3 and LPE16∶1(log rankx2=4.475,5.763,P=0.034,0.016).Conclusion The serum levels of glycerophospholipid metabolites LPC18∶3 and LPE16∶1 in AECOPD patients were decreased,which were related to lung function status.The combination of the two may effectively evaluate the prognosis of AECOPD patients.
8.Changes in serum VILIP-1 and sTREM-1 levels in patients with acute cerebral hemorrhage and their correlation with the degree of neurological deficit and prognosis
Jiming JIN ; Yanjie WU ; Shilin YAN ; Zhanzeng LI ; Yang LIU
International Journal of Laboratory Medicine 2024;45(18):2223-2228
Objective To investigate the changes in the levels of serum visinin-like protein-1(VILIP-1)and soluble triggering receptor expressed on myeloid cells-1(sTREM-1)in patients with acute cerebral hem-orrhage(ACH)and their correlation with the degree of neurological deficits and prognosis.Methods Totally 115 cases of ACH patients admitted to this hospital from January 2021 to January 2023 were selected as the ACH group,and another 115 healthy volunteers with physical examination in the same period were selected as the control group.The ACH patients were divided into mild deficit group(39 cases),moderate deficit group(46 cases)and severe deficit group(30 cases)according to the degree of neurological deficit assessed by the national institutes of health stroke scale(NIHSS).Patients with ACH were divided into a poor prognosis group(27 cases)and a good prognosis group(88 cases)after 90 d of follow-up according to the prognosis as-sessed by the modified Rankin scale.Serum VILIP-1 and sTREM-1 levels were measured by enzyme-linked immunosorbent assay.Spearman correlation was used to analyze the correlation between NIHSS scores and se-rum VILIP-1 and sTREM-1 levels in ACH patients,a multifactorial Logistic regression model was set up to analyze the factors affecting the prognosis of ACH patients,and the predictive value of serum VILIP-1 and sTREM-1 levels in poor prognosis in ACH patients was analyzed by plotting the receiver operating character-istic(ROC)curve.Results Compared with the control group,serum VILIP-1 and sTREM-1 levels were ele-vated in the ACH group(P<0.05).Serum VILIP-1 and sTREM-1 levels increased sequentially in the mild-deficiency,moderate-deficiency,and severe-deficiency groups(P<0.05).Spearman correlation analysis showed a positive correlation between NIHSS scores and serum VILIP-1 and sTREM-1 levels in ACH patients(r=0.792 and 0.781,both P<0.001).After 90 d of follow-up,the incidence of poor prognosis in 115 ACH patients was 23.48%(27/115).Multifactorial Logistic regression analysis showed that increased hematoma volume and elevated NIHSS score,VILIP-1,and sTREM-1 were independent risk factors affecting the progno-sis of patients with ACH(P<0.05).ROC curve analysis showed that the area under the curve of serum VIL-IP-1 and sTREM-1 levels combined to predict poor prognosis in ACH patients was 0.872,which was greater than that of serum VILIP-1 and sTREM-1 levels alone,which were 0.784 and 0.772(P<0.05).Conclusion Ele-vated serum VILIP-1 and sTREM-1 levels in ACH patients are closely associated with increased degree of neurological deficit and poor prognosis,and the combined detection of serum VILIP-1 and sTREM-1 has high predictive value for poor prognosis in ACH patients.
9.Effects of flurochloridone on apoptosis and Nrf2/HO-1 and NFκB signaling pathways in mouse testis and TM4 cells
Shuqi ZHAO ; Yanna WANG ; Zhijing NI ; Fang TIAN ; Rui LI ; Jiming ZHANG ; Xiuli CHANG ; Zhijun ZHOU
Journal of Environmental and Occupational Medicine 2023;40(6):673-680
Background Flurochloridone (FLC) is toxic to male reproduction and can induce apoptosis of testicular tissue and supporting cells under oxidative stress. Of particular concern is whether nuclear factor-erythrocyte 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway and nuclear factor kappa B (NFκB) signaling pathway participate this process. Objective To observe apoptosis of testicular tissue and sertoli TM4 cells and alterations of Nrf2/HO-1 and NFκB signaling pathways in mice treated with FLC in vivo/in vitro. Methods (1) Animal experiment. Testis samples were harvested from male C57BL/6 mice after 28-day FLC (0, 3, 15, 75, and 375 mg·kg−1 per day) exposure via oral route. Malondialdehyde (MDA) and superoxide dismutase (SOD) in homogenate of testicular tissue were measured by colorimetry. Apoptosis of testicular tissue was evaluated by TUNEL staining. Expression and distribution of Nrf2 and NFκB were detected by immunohistochemistry. Protein expression levels of Nrf2, HO-1, NAD(P)H: quinone oxidoreductase 1 (NQO1), NFκB, inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), and phosphorylated recombinant inhibitory subunit of nuclear factor kappa-B alpha (P-IκBα) in testicular tissue homogenate were determined by Western blotting. (2) Cell experiment. TM4 cell lines were treated with 40, 80, 120, 160, and 200 μmol·L−1 FLC for 6 h, and cell viability was detected by CCK-8. After 6 h exposure to 40, 80, and 160 μmol·L−1 FLC, the apoptosis rate was detected by flow cytometry, and the protein expression levels of Nrf2, HO-1, NQO1, NFκB, IKKβ, and IκBα were detected by Western blotting. Results (1) Animal experiment. Apoptosis occurred in the interstitial and basal parts of spermatogenic tubules in male C57BL/6 mice after 28 days of oral FLC exposure. Compared with the control group, the MDA level in testicular tissue of the 375 mg·kg−1 FLC-treated group was significantly increased (P<0.05), and the SOD activity was significantly decreased (P<0.05). After 375 mg·kg−1 FLC exposure, apoptosis occurred in the interstitial and basal parts of spermatogenic tubules. The results of immunohistochemistry showed the expression of Nrf2 and NFκB in the interstitium and basal part of spermatogenic tubules of the treated groups. Compared with the control group, the protein levels of Nrf2, NQO1, P-IκBα, NFκB, and IKKβ in the 15, 75, and 375 mg·kg-1 groups were significantly increased (P<0.001), and the HO-1 protein level was significantly increased in the 375 mg·kg−1 group (P<0.001). (2) Cell experiment. Compared with the control group, the TM4 cell viabilities in the 40, 80, 120, 160, and 200 μmol·L−1 FLC-treated groups significantly decreased (P<0.01). The apoptosis rates were significantly increased (P<0.05), and the apoptosis rates increased from 5.7% in the control group to 7.4%, 9.4%, and 11.7% in the 40, 80, and 160 μmol·L−1, respectively. The Nrf2 protein level in the 40 μmol·L−1 group was significantly increased (P<0.01), while the levels significantly decreased in the 80 and 160 μmol·L−1 groups (P<0.01). The HO-1 protein levels in the 40, 80, and 160 μmol·L−1 groups were significantly increased (P<0.01). The level of NQO1 protein in the 40 μmol·L−1 group was significantly increased (P<0.01). The NFκB protein levels were significantly increased in the 80 and 160 μmol·L−1 groups (P<0.001). The IκBα protein levels were significantly decreased in all treated groups (P<0.001). The IKKβ protein had no significant change. Conclusion FLC induces testicular tissue apoptosis, and the process affects Nrf2/HO-1 signaling pathway and NFκB signaling pathway. The in vitro study confirms that FLC could induce apoptosis of TM4 cells and activate Nrf2/HO-1 and NFκB signaling pathways.
10.Impacts of cadmium on mouse neural stem cells based on dose-response metabomics
Yixi LI ; Jiming ZHANG ; Qiuyun GU ; Zheng WANG ; Bing ZHANG ; Zhijun ZHOU ; Xiuli CHANG
Journal of Environmental and Occupational Medicine 2023;40(8):892-899
Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl2 at designed doses (0, 0.5, 1.0, and 1.5 μmol·L−1). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L−1 dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.


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