1.Quercetin inhibits ferroptosis to alleviate intestinal ischemia-reperfusion injury
Xiaojie MA ; Yufang LENG ; Jialu MU ; Lingguo KONG
Journal of Army Medical University 2025;47(12):1301-1311
Objective To investigate the role of quercetin(QUE)in ferroptosis during intestinal ischemia-reperfusion(IR)injury and elucidate its underlying mechanisms.Methods ① Potential target genes of QUE were predicted using the TCMSP,PharmMapper,and SwissTargetPredictive databases.Target genes associated with intestinal IR injury and ferroptosis were collected from GeneCards,PharmGKB,and OMIM databases.After overlapping genes were identified and analyzed,protein-protein interaction(PPI)networks were constructed using the STRING database and then visualized with Cytoscape 3.10.0.Molecular docking was performed to validate the binding conformations between QUE and key targets.② In vivo experiments were conducted to verify QUE's protective effects against intestinal IR injury.Thirty-six SPF-grade male C57BL/6J mice(6~8 weeks old,body weight:22±2 g)were randomly divided into Sham,Sham+QUE,IR,IR+QUE,IR+QUE+erastin(IR+QUE+Era),and IR+QUE+kevetrin hydrochloride(IR+QUE+KH)groups,with 6 mice in each group.Mouse model of intestinal IR injury was induced by 45 min ischemia of the superior mesenteric artery followed by 60 min reperfusion.HE staining was used to observe histopathological changes in the intestinal tissues.ELISA was employed to the serum or intestinal contents of diamine oxidase(DAO),pro-inflammatory cytokines(TNF-α,IL-6,IL-1β),and ferroptosis markers[glutathione(GSH)and Fe2+].Western blotting was utilized to detect the protein expression of glutathione peroxidase 4(GPX4),acyl-CoA synthetase long-chain family member 4(ACSL4),and tumor protein 53(p53).Results ① Network pharmacology identified 460 QUE targets,1 552 intestinal IR injury targets,and 1 967 ferroptosis-related targets,and 92 overlapping genes were identified as potential therapeutic targets.Molecular docking revealed a strong binding affinity between QUE and p53(binding energy:-6.8 kcal/mol).② In vivo experiments demonstrated that the IR+QUE group exhibited reduced intestinal damage and lower Chiu's score(P<0.05),decreased serum DAO content but elevated intestinal DAO content(P<0.05),decreased levels of TNF-α,IL-6,and IL-1β in the serum and intestinal tissues(P<0.05),reduced Fe2+accumulation,and increased GSH content(P<0.05),and up-regulated GPX4(P<0.05)and down-regulated ACSL4 and p53 expression(P<0.05)at protein level when compared with the IR group.While,the administration of ferroptosis agonist Era,or p53 agonist KH resulted in diminished therapeutic effects of QUE(P<0.05)when compared with the IR+QUE group.Conclusion QUE alleviates intestinal IR injury by inhibiting ferroptosis,which may be associated with its down-regulating p53 expression.
2.Remimazolam attenuates intestinal ischemia-reperfusion injury in mice by regulating ferroptosis through CX43
Lingguo KONG ; Yufang LENG ; Xiaojie MA ; Jialu MU
Journal of Army Medical University 2025;47(15):1771-1781
Objective To investigate whether remimazolam attenuates intestinal ischemia-reperfusion(I/R)injury in mice by regulating ferroptosis through connexin-43(CX43).Methods Molecular docking was applied to predict the binding affinity of remimazolam to CX43.A total of 72 SPF-grade adult male C57BL/6J mice(6~8 weeks old,weighing 20~25 g)were subjected.Thirty of them were randomly divided into sham operation group(Sham group),I/R group 1,and I/R+10,20 and 40 mg/kg remimazolam groups(RM10,RM20 and RM40 groups),with 6 mice in each group.Another 30 mice were randomly assigned into 5 groups(n=6),I/R group 2,erastin group(E group),I/R+40 mg/kg remimazolam group 2(RM40 group 2),I/R+Fer-1 group(Fer-1 group),and erastin+40 mg/kg remimazolam group(ERM group).The left 12 mice were randomly and equally grouped into I/R+RM+oe-NC group(oe-NC group)and I/R+RM+oe-CX43 group(oe-CX43 group).The Fer-1 group was given an intraperitoneal injection of 5 mg/kg Fer-1 in 1 h prior to reperfusion,the E group was given 10 mg/kg erastin intraperitoneally 1 d before modeling,and all the remimazolam groups,the oe-NC group and the oe-CX43 group were injected intravenously with corresponding doses of remimazolam 30 min pre-modeling,while the oe-NC and oe-CX43 groups were injected with empty vector virus and overexpression of CX43 vector virus,respectively,48 h before the administration of remimazolam.A mouse intestinal I/R injury model was constructed by clamping the superior mesenteric artery for 45 min and reperfusion for 30 min.The small intestine tissues were harvested and observed for pathological changes,and the intestinal mucosal damage was assessed with Chiu's score.The contents of Fe2+,total iron,malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)were detected by colorimetric assay;the production of reactive oxygen species(ROS)was determined by DHE probe;the expression of ferroptosis-related genes was determined by RT-qPCR;and the expression levels of CX43,GPX4,and SLC7A11 were detected by Western blotting.Results Molecular docking indicated that remimazolam had a binding energy of-6.699 kcal/mol with CX43 protein,suggesting good binding affinity between them.Compared with the Sham group,the I/R group 1 showed increases in Chiu's scores and CX43 expression(P<0.05),along with pathological damage to intestinal tissues,and elevated contents of Fe2+,total iron,ROS and MDA(P<0.05),and down-regulated GPX4 and SLC7A11(P<0.05).Compared with the I/R group 1,Chiu's score was reduced in the RM40 group,and CX43 was significantly down-regulated(P<0.05),contents of Fe2+,total iron,ROS,and MDA were decreased(P<0.05),and expression levels of GPX4 and SLC7A11 were enhanced(P<0.05),and severity of intestinal histological damage was attenuated in both the RM40 and Fer-1 groups.Compared with the E group,the ERM group had the decreases in CX43 expression level(P<0.05),Fe2+,total iron,ROS,and MDA contents(P<0.05),and increases in GPX4 and SLC7A11 expression levels(P<0.05),with the improvement in intestinal tissue.Compared with the oe-NC group,overexpression of CX43 resulted in the increased CX43 expression,elevated contents of Fe2+,total iron,ROS and MDA(P<0.05)and decreased expression of GPX4 and SLC7A11(P<0.05),leading to the exacerbated injury in intestinal tissue.Conclusion Remimazolam attenuates intestinal I/R injury by inhibiting ferroptosis through down-regulating CX43 expression.
3.Design and verification of the pressure regulation module in underwater positive pressure protective suit
Qingwei HUANG ; Wanxin ZHANG ; Dongyue LIU ; Jialu MA ; Shaosong LI ; Hailong FAN ; Hao HUANG
Space Medicine & Medical Engineering 2025;36(2):159-163
Objective Maintain a sable differential pressure inside the Underwater Positive Pressure Protective Suit(UPPPS)to ensure normal breathing and safe underwater operations for the diver.Methods Utilize a pressure regulator as the UPPPS's pressure control valve to automatically maintain the differential pressure inside the suit.Results By establishing a physical model,the relationship between the steady-state differential pressure with the ventilation flow rate and the ambient pressure was obtained.(1)The ventilation flow rate is positively correlated with the steady-state differential pressure,the higher the ventilation flow rate,the greater the steady-state differential pressure.(2)At the same ventilation flow rate,the larger the ambient pressure is,the smaller the steady-state differential pressure is.Underwater unmanned and manned experiments using the UWT suit were conducted.The expermental results are in agreement with the theoretical analysis.Conclusion The performance of pressure regulator has been verified by the underwater experiments,it effectively stabilizes the differential pressure within the UPPPS.
4.Predict the effect of the number of positive preoperative serum tumor markers on the surgical method and prognosis of intrahepatic cholangiocarcinoma patients based on mediation analysis
Zonglong LI ; Jialu CHEN ; Yue TANG ; Delong QIN ; Chen CHEN ; Yinghe QIU ; Hong WU ; Yu HE ; Xianhai MAO ; Wenlong ZHAI ; Jingdong LI ; Xiao LIANG ; Chuandong SUN ; Kai MA ; Zhimin GENG ; Zhaohui TANG ; Zhiwei QUAN
Chinese Journal of Surgery 2024;62(7):685-696
Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.
5.Predict the effect of the number of positive preoperative serum tumor markers on the surgical method and prognosis of intrahepatic cholangiocarcinoma patients based on mediation analysis
Zonglong LI ; Jialu CHEN ; Yue TANG ; Delong QIN ; Chen CHEN ; Yinghe QIU ; Hong WU ; Yu HE ; Xianhai MAO ; Wenlong ZHAI ; Jingdong LI ; Xiao LIANG ; Chuandong SUN ; Kai MA ; Zhimin GENG ; Zhaohui TANG ; Zhiwei QUAN
Chinese Journal of Surgery 2024;62(7):685-696
Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.
6.Chinese surgical robot-assisted surgery for parotid tumor:a case report
Guiquan ZHU ; Zhongkai MA ; Chang CAO ; Jialu HE ; Jiawei HONG ; Ruiting REN ; Hui XIA ; Bing YAN ; Xiaoyi WANG ; Long-Jiang LI ; Chunjie LI
West China Journal of Stomatology 2024;42(2):262-267
Robotic surgery is known as the"third technological revolution"in the field of surgery,and is an important milestone in the development of modern surgery.However,our country's innovative surgical robot industry is still in its early stages,and it is only being utilized in certain surgical fields.To explore the effectiveness of the application of do-mestic surgical robot in oral and maxillofacial surgery,the author successfully completed a case of benign parotid tumor resection with the assistance of a domestic autonomous robot.The operation was successful,facial nerve function was preserved,and postoperative wound healing was good.
7.Prevalence of malnutrition in elderly patients with type 2 diabetes mellitus: a meta-analysis
Tong ZHANG ; Jinhan NAN ; Jialu LI ; Jianhui DONG ; Jiali GUO ; Jiarong HE ; Yuxia MA ; Lin HAN
Chinese Journal of Clinical Nutrition 2024;32(5):289-297
Objective:To systematically evaluate the prevalence of malnutrition in elderly patients with diabetes.Methods:A total of eight databases, namely PubMed, Embase, Web of Science, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), and VIP Database, were systematically searched for cross-sectional studies on malnutrition in elderly diabetic patients published from the inception of the databases to September 13, 2023. Two researchers independently conducted literature screening, data extraction, and quality assessment. Data analysis was performed using Stata 16.0 software.Results:A total of 22 studies were included, involving 6 349 elderly diabetic patients. Results of the meta-analysis showed that the overall prevalence of malnutrition in elderly patients with diabetes was 32.3% (95% CI: 0.21 to 0.43), and the prevalence of at-risk of malnutrition was 49.0% (95% CI: 0.31 to 0.67). Subgroup analysis showed that the prevalence of malnutrition in elderly diabetic patients with chronic complications (56.8%) was significantly higher than those without chronic complications (21.9%). Inpatients also showed a higher prevalence compared with outpatients and community (44.4%, 29.0%, and 18.5%, respectively). The prevalence of malnutrition as per mini-nutritional assessment scale was higher than that as per mini-nutritional assessment short-form scale (35.8% vs. 23.3%, P<0.05). There was no significant difference in the prevalence of malnutrition in elderly diabetic patients of different genders ( P>0.05). Conclusions:The prevalence of malnutrition and at-risk of malnutrition in elderly diabetic patients is high. In clinical practice, we should not only strengthen the early diagnosis of malnutrition in patients, but also emphasize the screening of malnutrition risk, implement timely corresponding interventions, and promote patient education on nutrition and health, to improve the prognosis and quality of life in elderly diabetes patients.
8.Clinical observation of growth and development,intellectual level,and psychological status in patients with juvenile-onset recurrent respiratory papilloma
Jialu SONG ; Yang XIAO ; Lijing MA ; Jun WANG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(6):391-394
OBJECTIVE Exploring the effects of juvenile-onset recurrent respiratory papillomatosis on growth and development,intellectual level,and psychological status.METHODS The clinical data of 40 patients with JORRP who attended Beijing Tongren Hospital of Capital Medical University from January to December 2023(observation group)and 40 healthy adolescents who had medical checkups at the hospital during the same period(control group)were retrospectively analyzed.The body mass index(BMI),Raven's standard progressive matrices(SPM),and the feelings of inadequacy scale(FIS)were used to evaluate the growth and development,intelligence level,and psychological status of the enrolled population.RESULTS BMI was(21.320±3.609)kg/m2 in the observation group and(22.250±2.685)kg/m2 in the control group.The difference between the two groups was not statistically significant(U=668.000,P>0.05).According to the standard conversion of SPM scores,the proportion of observation group with good intelligence level was 5%(2/40),average level was 55%(22/40),below average level was 35%(14/40),and low level was 5%(2/40),while 5%(2/40)of the control group had good intelligence,90%(36/40)had average intelligence,and 5%(2/40)had below average intelligence.The differences in SPM total scores and scores of perceptual discrimination ability in group A,series relationship ability in group D and abstract reasoning ability in group E between the two groups were statistically significant(P<0.05).The intelligence levels of both groups were related to their living areas(|r|>0.3,P<0.05).The difference in FIS scores between the observation group and the control group was statistically significant(86.650±21.680 vs.62.250±9.446,U=270.000,P<0.001).The age of first onset in the observation group was negatively correlated with its sense of inferiority(|r|>0.3,P<0.05).There was no correlation between the number of surgeries in the observation group and their intelligence level and FIS scores(|r|<0.3,P>0.05).CONCLUSION JORRP does not affect the growth and development of patients,but can increase their sense of inferiority to a certain extent,which has a negative impact on their mental health.
9.Long-term efficacy of type Ⅰ thyroplasty under general anesthesia in the treatment of unilateral vocal cord paralysis
Jun SHI ; Yang XIAO ; Jun WANG ; Chunhua XI ; Jialu SONG ; Lijing MA
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(10):657-660
OBJECTIVE To observe the long-term efficacy of type-Ⅰ thyroplasty under general anesthesia in the treatment of glottal insufficiency caused by unilateral vocal cord paralysis.METHODS A total of 52 patients with unilateral vocal cord paralysis who underwent type-Ⅰ thyroplasty under general anesthesia at Beijing Tongren Hospital from January 2017 to June 2023 were followed up for more than one year to analyze their efficacy.RESULTS All 52 patients underwent surgery successfully under general anesthesia,and hoarseness improved after operation.Coughing caused by drinking water was reduced or disappeared,and the vocal cords moved inward with improved glottal closure.One year after operation,there was no significant change in the position of the affected vocal cords compared to one week after surgery.The visual analog scale(VAS)scores of all patients with voice disorders decreased sequentially before surgery,one week after surgery,and one year after surgery(80.28±13.49 vs.37.78±19.15 vs.26.26±21.29,P<0.05).The preoperative and one-year postoperative voice perception assessment(GRBAS)showed statistically differences in grade(G),rough(R),breathy(B),and asthenia(A)scores(2.70±0.47 vs.1.09±0.66,2.52±0.54 vs.0.85±0.67,2.85±0.36 vs.0.67±0.65,2.74±0.44 vs.0.61±0.80,P<0.05)except for strain(S).Compared with preoperative results,one-year postoperatively showed a significant decrease in jitter and shimmer(4.61±2.61 vs.3.05±2.37,9.52±3.91 vs.7.11±2.78,P<0.05),and a significant prolongation of maximum phonation time(MPT)[(5.87±2.70)s vs.(14.50±4.30)s,P<0.05].No patients experienced perioperative adverse events.CONCLUSION Type-Ⅰ thyroplasty is an effective surgical method for treatment of vocal cord paralysis.The type-Ⅰ thyroplasty under general anesthesia is safe and effective,which not only significantly improves the symptoms of hoarseness in patients,but also has stable therapeutic effects and can maintain the results for a long time.At the same time,the patient has no pain during the procedure.
10.Correlation between intestinal flora characteristics and hepatic and renal impairments in HIV-infected heterosexual men
Mingjun MA ; Jialu HUANG ; Lidan ZHU ; Panpan CHEN ; Yong ZHANG ; Haoran ZHANG ; Qiuli XU ; Qianqian LIU ; Shaotan XIAO ; Xin XIN
Shanghai Journal of Preventive Medicine 2023;35(12):1192-1198
ObjectiveTo explore the relationship between the intestinal flora and the impairment of liver and kidney in HIV-infected men who have heterosexual sex with healthy women. MethodsFecal samples from 41 HIV-infected heterosexual men who have sex with women (PMSW) and 43 age- and BMI-matched healthy heterosexual men who have sex with women (NMSW) were collected and subjected to 16S rDNA sequencing. The blood levels of AST, ALT, TBIL, UREA, Cr, UA, β2-MG and other liver and kidney function indicators were measured. Bioinformatics methods were used to analyze the characteristics of the intestinal flora of the patients in these two groups, to compare the differential bacteria strains, and to analyze their correlation with liver and kidney function indicators. ResultsIn comparison with NMSW, the alpha diversity of intestinal flora was decreased in PMSW, and the beta diversity analysis showed significant differences in flora characteristics between the two groups (P<0.05). The abundance of Clostridium, Phylum thick-walled, Trichosporon, and Clostridium tumefaciens decreased but Fusobacteriota increased (LDA score >4). The comparison of liver and kidney function indexes revealed that AST, β2-MG levels were higher in PMSW than in NMSW, while TBIL was lower in PMSW than in NMSW. The number of patients with abnormal β2-MG was much higher in PMSW than in NMSW, and the difference was statistically significant (P<0.001). It was also found that AST was negatively correlated with Clostridium (P<0.05); TBIL was negatively correlated with Clostridium and positively correlated with Phylum thick-walled and Trichosporon (P<0.05). β2-MG was negatively correlated with Phylum thick-walled, Clostridium, Trichosporon and Rumenococcus (P<0.05) and positively correlated with Clostridium (P<0.05). ConclusionIn PMSW group, the alpha diversity of the flora is decreased. AST and β2-MG levels are increased, and TBIL level is decreased. These changes were significantly correlated with different strains of bacteria in the intestinal flora.

Result Analysis
Print
Save
E-mail