1.DEHP induces ferroptosis in testicular interstitial cells by inhibiting Fto expression
Fengqiong SUN ; Guowei ZHANG ; Lingqiao WANG ; Guiyong XU ; Chengwei GUO ; Yan SUN ; Rui YANG ; Lu ZHANG ; Guanghong YANG ; Ziyuan ZHOU ; Mingdan YOU
Journal of Army Medical University 2024;46(21):2369-2382
Objective To explore the role and mechanism of RNA demethylase fat mass and obesity-associated protein(FTO)in the ferroptosis in testicular interstitial cells induced by di(2-ethylhexyl)phthalate(DEHP).Methods Forty 3-week-old C57BL/6 male mice were randomly divided into a control group(corn oil)and 3 dosed DEHP treatment groups(5,250 and 500 mg/kg),and received an intragastric infusion of corresponding agents for 35 d,respectively.After mouse testicular interstitial TM3 cells was treated with 0,100,200 and 400 μmol/L mono-2-ethylhexyl phthalate(MEHP)for 24 h,corresponding plasmids were transfected to construct Fto overexpressing TM3 cells.Serum testosterone level was detected by ELISA,expression of testicular proteins was detected with immunohistochemical assay,and contents of Fe2+,malondialdehyde(MDA)and lipid peroxides in the testicle were detected by colorimetry.Methylated RNA immunoprecipitation,RT-PCR,and Western blotting were used to detect the level of N6-methyladenosine(m6A)modification.Results In the mice exposed to 250 and 500 mg/kg DEHP,the serum testosterone level was significantly reduced(P<0.01),contents of Fe2+,MAD and lipid peroxides in testicular tissue were obviously increased(P<0.01),and protein levels of RNA demethylase FTO,and ferroptosis related molecules ferritin heavy chain 1(FTH1)and glutathione peroxidase 4(GPX4)were significantly down-regulated(P<0.05),while those of transferrin receptor(TFRC),ferroportin(FPN),cyclooxygenase-2(COX-2),and acyl-CoA synthetase long-chain family member 4(ACSL4)were notably up-regulated(P<0.05).MEHP treatment for 24 h resulted in remarkably decreased cell viability in the TM3 cells,increased production of intracellular reactive oxygen species(ROS),reduced mitochondrial membrane potential(MMP)(P<0.01),down-regulated mRNA and protein levels of Fto(P<0.01),and the changes in other ferroptosis related proteins were consistent with the trend in testicular tissue,indicating ferroptosis in testicular interstitial cells.Intervention with ferroptosis inhibitor Fer-1 or overexpression of Fto significantly inhibited MEHP-induced toxicity and ferroptosis in TM3 cells(P<0.05),and overexpression of Fto reduced the m6A modification of Gpx4 and Fth1 mRNA(P<0.05).Conclusion Abnormal m6A modification of Gpx4 and Fth1 caused by inhibiting FTO expression may be the mechanism of ferroptosis in testicular interstitial cells induced by DEHP.
2.Effects of anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata in repairing destructive wounds and rebuilding function of hands or feet
Chengwei GE ; Guodong JIANG ; Junnan CHENG ; Liping GUO ; Zhigang CHE ; Song YUAN ; Jihui JU
Chinese Journal of Burns 2024;40(9):842-848
Objective:To investigate the effects of anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata in repairing destructive wounds and rebuilding function of hands or feet.Methods:This study was a retrospective observational study. From January 2022 to March 2023, 16 patients with destructive wounds in hands or feet combined with extensor tendon defects who met the inclusion criteria were admitted to Suzhou Ruihua Orthopedic Hospital, including 12 males and 4 females, aged 3 to 63 years. The wounds were located on the hands in 12 cases and on the feet in 4 cases. The number of defective extensor tendon ranged one to five, and the length of the defect ranged from 2.5 to 6.0 cm. The wound area was 11.0 cm×5.5 cm to 29.0 cm×9.5 cm after debridement. The wounds were repaired with anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata, and the flap area was 12.0 cm×6.5 cm to 30.0 cm×11.0 cm. The fascia lata was used to repair the extensor tendon defects, and the harvesting area of fascia lata was 8.0 cm×3.0 cm to 12.0 cm×8.0 cm. The wounds in flap donor areas in 15 patients were sutured directly, and the wound in flap donor area in 1 patient was covered with medium-thickness skin graft from lower abdomen. The survival of flaps and the wound healing in donor and recipient areas of flaps were observed within 1 week after operation. The number of patients who underwent thinning and plastic surgery or tenolysis was recorded during postoperative follow-up. At the last follow-up, the recovery of sensory function of the transplanted flaps on hands or feet was evaluated, the efficacy of flap repair was evaluated according to the comprehensive flap evaluation scale, and the function of hands was evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association. The following two indexes were compared, including the measured total active motion of the injured fingers and the foot function assessed using Maryland foot function scale between before surgery and at the last follow-up.Results:Arterial crisis occurred in flaps in 2 patients after operation, and the flaps survived after timely exploration; the flaps in the rest patients survived well after operation. No obvious scar hyperplasia or ulceration was observed in donor and recipient areas of flaps after operation. All patients were followed up for 8 to 16 months, of which 6 patients underwent flap thinning and plastic surgery 6 to 7 months after operation, and 4 patients underwent tenolysis 3 to 6 months after operation. At the last follow-up, the recovery of sensory function of flaps reached S1 level in 5 cases and S2 level in 11 cases, and the two-point discrimination only had 1 point. The efficacy of flap repair scored 80 to 91, which were evaluated as excellent in 5 cases, good in 9 cases, and acceptable in 2 cases. The hand function was evaluated as excellent in 5 cases, good in 5 cases, and acceptable in 2 cases. The active extension function of the injured finger/toe was reconstructed successfully, and the total active motion of the injured finger was (225±22)° at the last follow-up, which was significantly higher than (117±20)° before surgery ( t=119.59, P<0.05); the foot function score was 86±7 at the last follow-up, which was significantly higher than 29±7 before surgery ( t=222.68, P<0.05), and the foot function was evaluated as excellent in 2 cases, good in 1 case, and acceptable in 1 case. Conclusions:The operation of harvesting the anterolateral femoral perforator flap pedicled with oblique branch of lateral circumflex femoral artery is relatively simple. After the wounds on hands or feet being repaired with the flaps, the appearance and function are good, with no obvious scar hyperplasia in donor and recipient areas of flaps. The fascia lata carried by the flap can repair the extensor tendon defect at the same time and improve the movement of the finger/toe.
3.Correlation between CT-based arterial radiomics score and the neo-adjuvant treatment response of pancreatic cancer
Mengmeng ZHU ; Yun BIAN ; Chengwei CHEN ; Jian ZHOU ; Na LI ; Yifei GUO ; Ying LI ; Xiaohan YUAN ; Jieyu YU ; Jianping LU
Chinese Journal of Pancreatology 2024;24(3):190-197
Objective:To identify the relationship between the CT arterial radiomics score and the treatment response to neoadjuvant therapy for pancreatic cancer.Methods:The clinical data of 243 pancreatic cancer patients who received surgical resection after neo-adjuvant therapy in the First Affiliated Hospital of Naval Medical University from March 2017 to March 2023 were retrospectively analyzed. Based on the tumor regression grade (TRG), the patients were divided into good response group (TRG 0-1, n=30) and non-good response group (TRG 2-3, n=213). The clinical, radiological and pathological features were compared between two groups. Fully-automated segmentation tool was used for segmenting the arterial CT scan of pancreatic tumor before and after treatment. Python package was applied to extract the radiomics features of tumors after segmentation and the extracted features were reduced and chosen using the least absolute shrinkage and selection operator (Lasso) logistic regression algorithm. Lasso logistic regression formula was applied to calculate the arterial radiomics score. Univariate and multivariate logistic regression models were used to analyze the association between arterial radiomics score and treatment response to neoadjucant therapy. Receiver operating-characteristics (ROC) curve was drawn and area under curve (AUC), specificity, sensitivity and accuracy for evaluating the treatment response were calculated. The clinical usefulness of arterial radiomics score for diagnosing the response of neoadjuvant treatment for pancreatic cancer were determined by decision curve analysis (DCA) . Results:A total of 330 arterial radiomics CT features were obtained, and 9-selected arterial phase features associated with treatment response were determined after being reduced by the Lasso logistic regression algorithm. Univariate analysis showed that the arterial radiomics score, three-dimensional diameter after neoadjuvant therapy, pancreatic contour, T stage, N stage, Peri-pancreatic nerve invasion, lymph-vascular space invasion (LVSI) and invasion of duodenum were all associated with treatment response (all P value <0.05). Multivariate logistic regression analyses confirmed that arterial radiomics score was obviously associated with the neoadjuvant treatment response ( P<0.001). At the cut-off value of 1.93, AUC of the arterial radiomics score for diagnosing neoadjuvant treatment response was 0.92, and the specificity, sensitivity and accuracy was 86.7%, 84.5% and 84.8%. DCA demonstrated that when the percentage for predicting the treatment response by using the arterial radiomics score was >0.2, the patients could benefit from the application of arterial radiomics score for evaluating neoadjuvant therapy response. Conclusions:The arterial radiomics score was strongly correlated with the neoadjuvant treatment response of pancreatic cancer, and can accurately predict neoadjuant treatment efficacy.
4.Synthesis and antibacterial activity of water-soluble limonin benzoylhydrazone derivatives
Chengwei YANG ; Yali GUO ; Caolong LI
Journal of China Pharmaceutical University 2022;53(3):273-277
As a compound rich in citrus plants, limonin has a wide range of biological activities, but its practical application is limited because of its poor water solubility.In this paper, eight new compounds 7a-7h were designed and synthesized by introducing benzoyl hydrazone at the carbonyl position of limonin.The results showed that the water solubilities of all compounds were higher than that of limonin, especially 7a, 7d, 7e and 7f.In addition, the experiment showed that compounds 7d and 7e with substituted hydroxyl groups at the interposition and para-position of the benzene ring had strong antibacterial effects against Escherichia coli and Staphylococcus aureus, and that compound 7e had the best activity, with minimum inhibitory concentrations of 0.31 mg/mL and 1.25 mg/mL, respectively.And compound 7e had better antibacterial activiy in E.coli than sodium benzoate.
5.Predictive value of mNUTRIC score for chronic critical illness in elderly patients with sepsis
Lingling WANG ; Rui CHEN ; Jiahui DONG ; Chengwei LEI ; Richeng XIONG ; Zhenhui GUO
Chinese Journal of Emergency Medicine 2022;31(1):73-77
Objective:To explore the predictive value of the modified NUTrition risk in the critically ill (mNUTRIC) score for chronic critical illness (CCI) in elderly sepsis patients.Methods:A prospective observational study was conducted. Elderly sepsis patients admitted to Medical Intensive Care Unit (MICU) of General Hospital of Southern Theatre Command for more than 24 h from August 2019 to January 2021 were enrolled. Age, sex, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, acute gastrointestinal injury (AGI) score, clinical frailty score and mNUTRIC score at admission, length of ICU stay, usage of mechanical ventilation and renal replacement therapy were recorded. According to the occurrence of CCI, patients were divided into the CCI group and rapid recovery (RAP) group, and the differences between the two groups were compared. The risk factor of CCI after sepsis in elderly patients were analyzed by log-binomial regression analysis. Receiver operating characteristic (ROC) analysis was performed for mNUTRIC score. Differences were considered significant at P<0.05. Results:Of the enrolled 91 sepsis patients, 14 (15%) patients died within the first week, 37 (41%) exhibited RAP and 40 (44%) developed CCI. The CCI patients were significantly older and presented a higher APACHE Ⅱ score, CFS score, mNUTRIC score, and usage of mechanical ventilation and renal replacement therapy compared with the RAP patients ( P<0.05). Multivariate regression analysis revealed that mNUTRIC score was an independent risk factor for the development of CCI in elderly sepsis patients, prevalence ratio was 1.503 (95% CI: 1.007-2.244). The area under the curve (AUC) of mNUTRIC score was 0.706 (95% CI: 0.592-0.805). Conclusions:The mNUTRIC score at the time of admission in the intensive care unit can be used to predict CCI after sepsis in elderly sepsis patients.
6.Development and clinical evaluation of an equipment with artificial intelligence real-time assistance in detection of gastrointestinal protruding lesions under endoscopy
Zhiyin HUANG ; Jingsun JIANG ; Qiongying ZHANG ; Qinghua TAN ; Hui GONG ; Linjie GUO ; Chuanhui LI ; Jiang DU ; Huan TONG ; Bing HU ; Jie SONG ; Chengwei TANG ; Jing LI ; Ling LIU
Chinese Journal of Digestion 2020;40(11):745-750
Objective:To develop an diagnostic equipment with artificial intelligence (AI) real-time assistance under endoscopy (endoscopic AI equipment) for the detection of gastrointestinal protruding lesions, and to evaluate its performance and safety.Methods:From January to December 2017, at Endoscopy Center of West China Hospital, Sichuan University, the endoscopic images of individuals who underwent routine gastroscopy and colonoscopy were collected. The model was established based on convolutional neural network and the endoscopic AI equipment was developed. From June to December 2019, a prospective, single center, blinded and parallel controlled study was conducted to compare the differences in evaluation of protruding lesions of the same patient under gastroscopy or colonoscopy between endoscopist and the endoscopic AI equipment and to evaluated the impact of lesion size (lesions <5 mm and ≥5 mm) on the detection of endoscopic AI equipment. The main outcome measure was the detection time difference in reporting the protruding lesion between endoscopic AI equipment and endoscopist; and the secondary indicator was the accuracy of endoscopic AI equipment in detecting the protruding lesion. Wilcoxon rank sum test and chi-square test were used for statistical analysis.Results:A total of 71 582 white light endoscopy images were used for endoscopic AI equipment training, which included 41 376 images of protruding lesions. The endoscopic AI equipment was successfully developed and obtained the registration certificate of medical devices of the People′s Republic of China (Sichuan Instrument Standard, 20202060049). The accuracy, sensitivity, and specificity of endoscopic AI equipment in detecting protruding lesions were 96.4%, 95.1% and 92.8%, respectively. The detection time of each protruding lesions under gastroscopy of endoscopic AI equipment was 1.524 seconds faster than that of endoscopist; but the detection time of each protruding lesions under colonoscopy was 0.070 seconds slower than that of endoscopist, and the differences were statistically significant ( Z=-5.505 and -4.394, both P<0.01). The detection time of each protruding lesions under gastroscopy or colonoscopy of endoscopic AI equipment was not inferior to that of endoscopist. The detection rate of protruding lesions under colonoscopy by endoscopic AI equipment was 89.9% (249/277) and the sensitivity was 89.9%; the detection rate of protruding lesions under colonoscopy was 87.0% (450/517) and the sensitivity was 86.9%. There were no statistically significant differences in the detection time difference, sensitivity and missed diagnostic rate between the lesions <5 mm and ≥5 mm detected by endoscopic AI equipment under gastroscopy (all P>0.05). The sensitivity of endoscopic AI equipment in detecting the lesions ≥5 mm under colonoscopy was higher than that of lesions <5 mm (96.8% vs. 84.9%), and the missed diagnostic rate was lower than that of lesions <5 mm (3.2%, 3/94 vs. 15.1%, 61/405), and the differences were statistically significant ( χ2=9.615 and 9.612, both P=0.002). No adverse events on patients and medical staffs occurred, and there were no cases of equipment electricity leakage, and abnormal work reported during the use of endoscopic AI equipment. Conclusions:The endoscopic AI equipment can report the protruding lesions simultaneously with endoscopists, and the accuracy is close to 90%, which is expected to be a practical assistant for endoscopists to avoid missed detection of protruding lesions.
7. Molecular epidemiology of Listeria monocytogenes isolated from ready-to-eat food in 2017 in China
Weiwei LI ; Yunchang GUO ; Li ZHAN ; Guozhu MA ; Zushun YANG ; Chengwei LIU ; Zhixin SHEN ; Di WANG ; Xiaoai ZHANG ; Xiaohong SONG ; Bo YU ; Huayun JIA ; Xiugui LI ; Xiuli ZHANG ; Xiaorong YANG ; Dajin YANG ; Xiaoyan PEI
Chinese Journal of Preventive Medicine 2020;54(2):175-180
Objective:
To analyze the molecular characteristics of
8.Clinical observation and study of hormone replacement therapy on postoperative cervical squamous cell carcinoma
Chengwei HE ; Tianqi GUO ; Ping LEI ; Caixia LU
Clinical Medicine of China 2020;36(2):113-117
Objective:To observe the clinical effect of hormone replacement therapy(HRT) on patients with cervical squamous cell carcinoma after operation and its effect on sex hormone, blood fat, bone content and tumor markers, and to evaluate the clinical significance of HRT therapy.Methods:From January 2016 to January 2019, a total of 100 patients with cervical squamous cell carcinoma admitted to Zhuhai Maternal and Child Health Hospital were analyzed retrospectively.After surgical treatment, 50 patients were willing to receive hormone replacement therapy as the experimental group and 50 patients received routine treatment as the control group, Kupperma score was used to evaluate the severity of perimenopausal symptoms, and the serum levels of sex hormones, blood fat, bone content and tumor markers in the two groups before and after treatment were detected and the occurrence of adverse reactions were evaluated.Results:Before treatment, there was no significant difference in kupperma score, estradiol, follicle-stimulating hormone, luteinizing hormone level, lipid level, bone content and tumor marker level between the two groups(all P>0.05). After HRT treatment, kupperma score in the experimental group was significantly lower than that before treatment((11.47±5.12) vs.(20.46±7.52), t=7.262). In the detection of sex hormones, the levels of estradiol in the experimental group was significantly increased((39.26±7.43) ng/L vs.(13.78±7.52) ng/L, t=12.345), and the levels of follicle stimulating hormone((34.25±7.61) U/L vs.(62.18±19.12) U/L, t=8.245)and luteinizing hormone((20.31±6.25) U/L vs.(35.08±6.27) U/L, t=5.452, P=0.004) in the experimental group were significantly decreased.In the detection of blood lipid level, bone content and tumor markers, high-density lipoprotein((1.62±0.33) mmol/L vs(1.34±0.26) mmol/L, t=4.592, P=0.008) and alkaline phosphatase levels((66.21±25.75) U/L vs.(46.88±9.06) U/L, t=5.912, P=0.001)was significantly increased, the low density lipoprotein((2.78±0.43) mmol/L vs.(2.87±0.78) mmol/L, t=4.265, P=0.012)and total cholestenone((4.02±0.45) mmol/L vs.(4.23±0.91) mmol/L, t=5.761, P=0.002) levels were significantly decreased in the experimental group, with statistically significant differences(all P<0.05). There was no significant difference in the level of serum SCC antigen between the experimental group and the control group before and after treatment ( P> 0.05); there was no significant difference in the above indicators between the experimental group and the control group before and after treatment ( P> 0.05); there was no significant increase in adverse reactions such as breast swelling and pain (3 cases), body mass increase (2 cases), bleeding (1 case), body pain (4 cases), vomiting (4 cases), etc. between the experimental group and the control group (2, 1, 2, 3, 1 case) There was no statistical significance ( P> 0.05). Conclusion:HRT treatment of cervical squamous cell carcinoma patients after surgery can significantly improve the peri menstrual syndrome caused by low estrogen level, and did not significantly increase the risk of recurrence of cervical cancer patients and adverse reactions.
9. Differential diagnosis of single inflammatory pseudotumor and peripheral lung cancer with 320-slice CT dual-input perfusion imaging
Chinese Journal of Medical Imaging Technology 2019;35(8):1214-1219
Objective:To explore the value of dual-input perfusion imaging (DI-CTP) in differential diagnosis of single inflammatory pseudotumor and peripheral lung cancer with 320-slice CT. Methods: Totally 52 patients with single pathological proved peripheral lung cancer (28 with adenocarcinoma, 24 with squamous cell carcinoma) and 21 patients with inflammatory pseudoaneurysm were enrolled. Pulmonary artery flow (PF) and bronchial artery flow (BF) were obtained, the perfusion index (PI) and total perfusion (TLP) were calculated. Time-density curve was obtained from DI-CTP, and the enhanced time to peak (TTP) were calculated. The above indexes were analyzed among squamous cell carcinoma, adenocarcinoma and inflammatory pseudotumor, and their values in differential diagnosis of peripheral lung cancer and inflammatory pseudotumor were evaluated. Results: There were significant differences of PF and TTP among squamous cell carcinoma, adenocarcinoma and inflammatory pseudotumor (all P<0.01), also of PF, TLP and TTP between inflammatory pseudotumors and peripheral lung cancer (all P<0.01). AUC of TTP was 0.99 (P<0.01), which had high diagnostic value. Taken TTP=16.3 s as the critical value, the sensitivity and specificity in predicting inflammatory pseudotumors and peripheral lung cancer was 100% and 95.0%, respectively. AUC of PF and TLP was 0.76 (P<0.01) and 0.71 (P<0.01), respectively, which had moderate diagnostic value. Conclusion: Inflammatory pseudotumor and peripheral lung cancer both have pulmonary artery and bronchial artery blood supply. TTP is helpful to differential diagnosis of inflammatory pseudotumor and peripheral lung cancer.
10.Effects of transjugular intrahepatic portosystemic shunt combined with left gastric vein embolization on the liver function of patients with liver cirrhosis
Hui HUAN ; Huan TONG ; Bo WEI ; Zhiyin HUANG ; Xiaodan LI ; Linjie GUO ; Xiaoping LI ; Hao WU ; Chengwei TANG
Chinese Journal of Digestion 2017;37(6):404-410
Objective To compare the difference in the effects on liver function between transjugular intrahepatic portosystemic shunt (TIPS) alone and the combination of TIPS and left gastric vein embolization (LGVE) in patients with liver cirrhosis.Methods This research was a retrospective study.From September 2014 to September 2015,31 patients with liver cirrhosis underwent TIPS (TIPS group) and 29 patients with liver cirrhosis underwent TIPS combined with LGVE (TIPS+LGVE group) were enrolled.The data of the liver function of patients before and after operation were collected and the Child-Pugh score and model for end-stage liver disease (MELD) were also calculated.Student's t test and chi-squared test were performed for statistical analysis.Results The preoperative portal vein pressures of TIPS group and TIPS+LGVE group were (28.48±2.77) mmHg (1 mmHg=0.133 kPa) and (28.38± 2.92) mmHg,respectively.And after operation,the portal vein pressures decreased to (17.81 ± 1.47) mmHg and (17.97 ± 2.04) mmHg,respectively,and the differences were both statistically significant (t=18.908 and 11.648,both P<0.01).At 12 months after operation,Child-Pugh score of TIPS+ LGVE group was 5.69 ± 1.19,which was significantly lower than that before operation (7.03±1.76),and the difference was statistically significant (t=3.398,P=0.001),which was also lower than that of TIPS group at the same time point (6.52 ± 1.54),and the difference was statistically significant (t =2.303,P=0.025).At 12 months after operation,the component ratio of patients with Child-Pugh grade A of TIPS±LGVE group was 89.7% (26/29),which was higher than that before operation (44.8%,13/29),and the difference was statistically significant (x2=13.228,P<0.01).The component ratio of patients with Child-Pugh grade B was 6.9 % (2/29),which was lower than that before operation (41.4 %,12/29),and the difference was statistically significant (x2 =9.416,P< 0.01).Conclusions TIPS significantly reduces portal vein pressure in patients with liver cirrhosis and it does not deteriorate liver function of patients in the long term.The combination of TIPS and LGVE is better than TIPS alone in improving liver function in patients with liver cirrhosis,especially in improvig long-term liver function in patients of Child-Pugh A and B grade.

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