1.Effects of a ferroptosis inhibitor on the apoptosis of photoreceptor cells and the Notch pathway in rats with retinal photochemical damage
Wenwen LI ; Hansheng WANG ; Shimiao ZONG ; Xiaoping YU
Recent Advances in Ophthalmology 2025;45(6):429-434
Objective To investigate the effects of the ferroptosis inhibitor Ferrostatin-1 on the apoptosis of photore-ceptor cells and the Notch pathway in rats with retinal photochemical damage(RPD).Methods Male Sprague-Dawley(SD)rats were randomly divided into the Control group(normally fed rats,intraperitoneal injection of an equal volume of saline),RPD group(RPD model rats,intraperitoneal injection of an equal volume of saline),Ferrostatin-1 group(RPD model rats,intraperitoneal injection of 5 mg·kg-1 Ferrostatin-1),and Ferrostatin-1+JFC group[RPD model rats,intrap-eritoneal injection of 5 mg·kg-1 Ferrostatin-1 and 0.5 mg·kg-1 Jagged1/FC chimeric protein(JFC,a Notch pathway acti-vator)],with 15 rats in each group.The retinal histopathology of rats in each group was evaluated via hematoxylin-eosin(HE)staining.The apoptosis of photoreceptor cells was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay.The expression level of ferrous ions(Fe2+),lactate dehydrogenase(LDH),malondialde-hyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in retinal tissues was measured using corresponding kits.Western blot was performed to assess the protein expression of transferrin receptor protein 1(TfR1),divalent metal transporter 1(DMT1),nuclear factor erythroid 2-related factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),recombinant glutathione peroxidase 4(GPX4),cleaved Caspase-3,Notch,and hairy and enhancer of split 1(Hes1).Results The thickness of the outer nuclear layer(ONL)in the Control group,RPD group,Ferrostatin-1 group,and Fer-rostatin-1+JFC group was(35.24±1.76)μm,(16.83±1.14)μm,(27.56±1.39)μm,and(21.48±1.23)μm,respec-tively;the apoptosis rate of photoreceptor cells in the four groups was(1.32±0.07)%,(18.57±1.63)%,(9.61±1.04)%,and(15.43±1.38)%,respectively.Compared with the Ferrostatin-1 group,the Ferrostatin-1+JFC group exhib-ited an aggravated retinal damage level,reduced ONL thickness,and increased apoptosis rate,and the differences were statistically significant(all P<0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expres-sion level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the RPD group were higher than those in the Control group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Control group,and the differences were statistically significant(all P<0.05).Compared with the RPD group,the Ferrostatin-1 group displayed a decrease in the expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 but an increase in the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4,and the differences were statistically significant(all P<0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the Ferrostatin-1+JFC group were higher than those in the Ferrostatin-1 group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Ferrostatin-1 group,and the differences were statistically significant(all P<0.05).Conclusion Fer-rostatin-1 may alleviate retinal oxidative stress and the apoptosis of photoreceptor cells in RPD rats by inhibiting the Notch pathway,thereby mitigating retinal damage.
2.Comparison of detection and manifestations of metastatic hepatocellular carcinoma by ultrasound at different frequencies
Hong QIN ; Yuli ZHU ; Qiannan ZHAO ; Feihang WANG ; Hansheng XIA ; Wentao KONG ; Wenping WANG
Chinese Journal of Clinical Medicine 2025;32(3):500-504
Objective To explore the value of high-frequency ultrasound in the detection of metastatic hepatocellular carcinoma and displaying lesion characteristics. Methods A total of 38 paitients with hepatocellular carcinoma satellite lesions within 40 mm of subcutaneous tissue were underwent low-frequency (1-5 MHz) and high-frequency (6-9 MHz) ultrasound. Detection rates and ultrasonic features were compared. Results High-frequency grayscale ultrasound had a higher detection rate (71.1% vs. 36.8%, P<0.001). Subgroup analysis showed higher detection rates with chemotherapy history (88.9% vs. 33.3%, P=0.002), fatty liver (71.9% vs 31.3%, P<0.001) or superficial lesion (within 20 mm, 76.5% vs 41.2%, P=0.031). High-frequency ultrasound also showed clearer margins (P=0.004) and more arterial-phase rim enhancement (P=0.007). Conclusions 6-9 MHz ultrasound detects metastatic hepatocellular carcinoma, especially superficial lesions, more effectively than 1-5 MHz ultrasound and better visualizes characteristics.
3.Effects of a ferroptosis inhibitor on the apoptosis of photoreceptor cells and the Notch pathway in rats with retinal photochemical damage
Wenwen LI ; Hansheng WANG ; Shimiao ZONG ; Xiaoping YU
Recent Advances in Ophthalmology 2025;45(6):429-434
Objective To investigate the effects of the ferroptosis inhibitor Ferrostatin-1 on the apoptosis of photore-ceptor cells and the Notch pathway in rats with retinal photochemical damage(RPD).Methods Male Sprague-Dawley(SD)rats were randomly divided into the Control group(normally fed rats,intraperitoneal injection of an equal volume of saline),RPD group(RPD model rats,intraperitoneal injection of an equal volume of saline),Ferrostatin-1 group(RPD model rats,intraperitoneal injection of 5 mg·kg-1 Ferrostatin-1),and Ferrostatin-1+JFC group[RPD model rats,intrap-eritoneal injection of 5 mg·kg-1 Ferrostatin-1 and 0.5 mg·kg-1 Jagged1/FC chimeric protein(JFC,a Notch pathway acti-vator)],with 15 rats in each group.The retinal histopathology of rats in each group was evaluated via hematoxylin-eosin(HE)staining.The apoptosis of photoreceptor cells was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay.The expression level of ferrous ions(Fe2+),lactate dehydrogenase(LDH),malondialde-hyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in retinal tissues was measured using corresponding kits.Western blot was performed to assess the protein expression of transferrin receptor protein 1(TfR1),divalent metal transporter 1(DMT1),nuclear factor erythroid 2-related factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),recombinant glutathione peroxidase 4(GPX4),cleaved Caspase-3,Notch,and hairy and enhancer of split 1(Hes1).Results The thickness of the outer nuclear layer(ONL)in the Control group,RPD group,Ferrostatin-1 group,and Fer-rostatin-1+JFC group was(35.24±1.76)μm,(16.83±1.14)μm,(27.56±1.39)μm,and(21.48±1.23)μm,respec-tively;the apoptosis rate of photoreceptor cells in the four groups was(1.32±0.07)%,(18.57±1.63)%,(9.61±1.04)%,and(15.43±1.38)%,respectively.Compared with the Ferrostatin-1 group,the Ferrostatin-1+JFC group exhib-ited an aggravated retinal damage level,reduced ONL thickness,and increased apoptosis rate,and the differences were statistically significant(all P<0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expres-sion level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the RPD group were higher than those in the Control group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Control group,and the differences were statistically significant(all P<0.05).Compared with the RPD group,the Ferrostatin-1 group displayed a decrease in the expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 but an increase in the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4,and the differences were statistically significant(all P<0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the Ferrostatin-1+JFC group were higher than those in the Ferrostatin-1 group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Ferrostatin-1 group,and the differences were statistically significant(all P<0.05).Conclusion Fer-rostatin-1 may alleviate retinal oxidative stress and the apoptosis of photoreceptor cells in RPD rats by inhibiting the Notch pathway,thereby mitigating retinal damage.
4.Activation of α7 nAChR improves white fat homeostasis and promotes beige adipogenesis and thermogenesis in obese mice
Hansheng BAO ; Sutong WANG ; Mujie LÜ ; Yongcheng WANG ; Ping JIANG ; Xiao LI
Journal of Southern Medical University 2024;44(3):499-506
Objective To investigate the effects of α7 nicotinic acetylcholine receptor(nAChR)agonist on β3-adrenoceptor agonist-induced impairment of white fat homeostasis and beige adipose formation and heat production in obese mice.Methods Forty obese C57BL/6J mice were randomized into high-fat feeding group,β3-adrenoceptor agonist-treated model group,α7 nAChR agonist group,and α7 nAChR inhibitor group(n=10),with another 10 mice with normal feeding as the blank control group.White adipose tissue from the epididymis of the mice were sampled for HE staining of the adipocytes.The expression levels of TNF-α,IL-1β,IL-10 and TGF-β in the white adipose tissue were determined by ELISA,and the mRNA levels of iNOS,Arg1,UCP-1,PRDM-16 and PGC-1α were detected using RT-qPCR.Western blotting was performed to detect the expression levels of NF-κB P65,p-JAK2,p-STAT3 in the white adipose tissue.Results Compared with those in the blank control group,the mice with high-fat feeding showed significantly increased body weight,more fat vacuoles in the white adipose tissue,increased volume of lipid droplets in the adipocytes,upregulated iNOS mRNA expression and protein expression of TNF-α and IL-1β,and lowered expression of Arg-1 mRNA and IL-10 and TGF-β proteins(P<0.01).Treatment with α7 nAChR significantly reduced mRNA levels of PRDM-16,PGC-1α and UCP-1,lowered TNF-α and IL-1β expressions,increased IL-10 and TGF-β expressions,and reduced M1/M2 macrophage ratio in the white adipose tissues(P<0.05 or 0.01).Conclusion Activation of α7 nAchR improves white adipose tissue homeostasis impairment induced by β3 agonist,promotes transformation of M1 to M2 macrophages,reduces inflammatory response in white adipose tissue,and promote beige adipogenesis and thermogenesis in obese mice.
5.Activation of α7 nAChR improves white fat homeostasis and promotes beige adipogenesis and thermogenesis in obese mice
Hansheng BAO ; Sutong WANG ; Mujie LÜ ; Yongcheng WANG ; Ping JIANG ; Xiao LI
Journal of Southern Medical University 2024;44(3):499-506
Objective To investigate the effects of α7 nicotinic acetylcholine receptor(nAChR)agonist on β3-adrenoceptor agonist-induced impairment of white fat homeostasis and beige adipose formation and heat production in obese mice.Methods Forty obese C57BL/6J mice were randomized into high-fat feeding group,β3-adrenoceptor agonist-treated model group,α7 nAChR agonist group,and α7 nAChR inhibitor group(n=10),with another 10 mice with normal feeding as the blank control group.White adipose tissue from the epididymis of the mice were sampled for HE staining of the adipocytes.The expression levels of TNF-α,IL-1β,IL-10 and TGF-β in the white adipose tissue were determined by ELISA,and the mRNA levels of iNOS,Arg1,UCP-1,PRDM-16 and PGC-1α were detected using RT-qPCR.Western blotting was performed to detect the expression levels of NF-κB P65,p-JAK2,p-STAT3 in the white adipose tissue.Results Compared with those in the blank control group,the mice with high-fat feeding showed significantly increased body weight,more fat vacuoles in the white adipose tissue,increased volume of lipid droplets in the adipocytes,upregulated iNOS mRNA expression and protein expression of TNF-α and IL-1β,and lowered expression of Arg-1 mRNA and IL-10 and TGF-β proteins(P<0.01).Treatment with α7 nAChR significantly reduced mRNA levels of PRDM-16,PGC-1α and UCP-1,lowered TNF-α and IL-1β expressions,increased IL-10 and TGF-β expressions,and reduced M1/M2 macrophage ratio in the white adipose tissues(P<0.05 or 0.01).Conclusion Activation of α7 nAchR improves white adipose tissue homeostasis impairment induced by β3 agonist,promotes transformation of M1 to M2 macrophages,reduces inflammatory response in white adipose tissue,and promote beige adipogenesis and thermogenesis in obese mice.
6.Epidemiological investigation of occupational hand-arm vibration disease caused by handheld workpiece polishing
Siyu PAN ; Maosheng YAN ; Bin XIAO ; Yanxia JIA ; Hanjun ZHENG ; Yongjian JIANG ; Hansheng LIN ; Mei WANG
China Occupational Medicine 2024;51(1):65-69
ObjectiveTo explore the influencing factors of occupational hand-arm vibration disease (OHAVD) caused by handheld workpiece polishing. Methods A total of 222 OHAVD patients (case group), 275 hand-transmitted vibration-exposed workers (exposed group) and 243 healthy workers without hand-transmitted vibration exposure (control group) in a sports equipment manufacturing enterprise were selected as the study subjects using the convenience sampling method. Worksite survey of occupational health was conducted on these three groups, and the human vibration measurement equipment was used to measure the vibration exposure level of handheld vibration among the study subjects. The 8-hour energy equivalent frequency-weighted vibrating acceleration [A(8)] and cumulative vibration exposure level (CVEL) were calculated. Results The prevalence of coldness, numbness, tingling fingers, and vibration-induced white finger was higher in the exposed group and the case group compared with the control group (all P<0.05). The prevalence of the above-mentioned hand symptoms was higher in the case group compared with the exposed group (all P<0.05). The A(8) and CVEL levels of the study subjects in the case group were higher than those in the exposed group (all P<0.05). Binary logistic analysis result showed that age and CVEL were both influencing factors of OHAVD (all P<0.05). According to the restricted cubic spline models, CVEL of the study subjects in the exposed group had a positive nonlinear dose-response relationship with the risk of OHAVD (overall trend P<0.01, nonlinear P<0.01), indicating an increasing risk of OHAVD with increasing CVEL. Conclusion Hand-transmitted vibration exposure is a risk factor for OHAVD. Early intervention should be carried out for hand-transmitted vibration-exposed individuals to reduce vibration-exposed levels and control vibration exposure time.
7.Distribution pattern of respiratory symptoms and the relevant risk factors in patients with pulmonary nodules: A cross-sectional study
Haijie XU ; Weitao ZHUANG ; Qi WANG ; Junhan WU ; Hansheng WU ; Yali CHEN ; Yong TANG ; Guibin QIAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(08):1175-1180
Objective To explore the distribution pattern of respiratory symptoms and relevant factors in patients with pulmonary nodules. Methods Demographic and clinical information were collected from patients who visited the Thoracic Surgery Outpatient Clinic of Guangdong Provincial People’s Hospital from January 2021 to January 2022. Hospital Anxiety and Depression Scale (HADS) was used to assess their anxiety and depression level. Results A total of 1 173 patients were enrolled, including 449 males and 724 females, with an average age of 46.94±11.43 years. Among the patients with pulmonary nodules, 37.7% of them had at least one respiratory symptom; 24.4% had cough, 14.0% had expectoration, 1.3% had hemoptysis and 14.9% had chest pain. Old age, male, exposure to second-hand smoking or environmental smoke, hair coloring and history of tuberculosis were major risk factors for respiratory symptoms (P<0.05). Middle age, old age, male, exposure to environmental smoke were major risk factors for cough (P<0.05); old age, smoking, larger maximum nodules diameters, exposure to environmental smoke and history of pneumonia were major risk factors for expectoration (P<0.05); male, multiple nodules, hair coloring, exposure to second-hand smoking and history of tuberculosis were major risk factors for chest pain (P<0.05). Symptomatic patients showed generally higher HADS scores than asymptomatic patients (P<0.001). Conclusion Cough, expectoration and chest pain are the predominant respiratory symptoms for patients with pulmonary nodules. The presentation of respiratory symptoms increases patients' anxiety and depression.
8.Analyzing the results of finger systolic blood pressure tests in 28 healthy young adults
Maosheng YAN ; Xi ZHONG ; Shanyu ZHOU ; Danying ZHANG ; Hansheng LIN ; Zhipeng HE ; Bin XIAO ; Qian LIU ; Chengmin WANG
China Occupational Medicine 2023;50(3):285-288
Objective To investigate the level of finger systolic blood pressure (FSBP) in healthy young adults. Methods A total of 28 healthy young adults were selected as the study subjects by convenient sampling method. The FSBP of the study subjects was detected at 30 and 10 ℃, and the FSBP index (Fi) was calculated. Results The FSBP of the study subjects at 30 and 10 ℃ were (102.0±16.5) and (104.4±15.2) mmHg, respectively. The FSBP in male group at 30 and 10 ℃ was (99.6±18.6) and (107.2±17.0) mmHg, respectively. The FSBP in female group at 30 and 10 ℃ was (104.4±13.9) and (101.5±2.8) mmHg, respectively. The results of factorial analysis showed that the interaction between gender and temperature on FSBP was statistically significant (P<0.05). FSBP in male group was higher at 10 than 30 ℃ (P<0.05) and higher than female group at 10 ℃ (P<0.05). There was no statistical significance for the main effect of gender, temperature, finger, or the interaction effect of gender and finger, temperature and finger for FSBP (all P>0.05). The average Fi of the study subjects was (98.0±16.6)%, with males and females having the average Fi of (100.7±20.7) % and (95.2±10.6) % respectively. The results of factorial analysis of variance showed that there was no significant difference on Fi in the main effect gender and fingers or the interaction effect between them(all P>0.05). Conclusion The FSBP test could be used as a detection method for assessing peripheral microcirculation function in Chinese population. However, further research is needed to establish reference ranges and influencing factors.
9.Risk factors for perioperative hypotension in severe patients after liver cancer surgery
Bin WANG ; Hansheng LIANG ; Yi FENG ; Youzhong AN
Journal of Clinical Hepatology 2022;38(3):572-576
Objective To investigate the risk factors for perioperative hypotension in severe patients after liver cancer surgery and its influence on prognosis. Methods A retrospective analysis was performed for the clinical data of 422 patients who underwent surgical treatment due to primary liver cancer or metastatic liver cancer and were then admitted to the intensive care unit (ICU) of Peking University People's Hospital from January 2014 to December 2019. The 107 patients requiring continuous intraoperative or postoperative pumping of vasoactive drugs (norepinephrine, dopamine, phenylephrine, and epinephrine) to maintain blood pressure were included in the hypotension group, and the 315 patients who did not require the pumping of vasoactive drugs to maintain blood pressure were included in the non-hypotension group. Related clinical data were collected from all patients, including sex, age, body mass index, history of liver surgery, comorbidities, underlying liver diseases, preoperative laboratory examinations, surgical data, and anesthesia, and the two groups were compared in terms of related prognostic indicators (in-hospital mortality, length of ICU stay, length of hospital stay, duration of mechanical ventilation, acute kidney injury, hypoxemia, pulmonary infection, and myocardial injury). The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The clinical indices with P < 0.1 were included in the binary logistic regression analysis to investigate the risk factors for hypotension. Results The overall mortality rate was 1.9% for the severe patients after liver cancer surgery, with a mortality rate of 3.7% in the hypotension group and 1.3% in the non-hypotension group. Compared with the non-hypotension group, the hypotension group had a significantly longer length of ICU stay ( Z =-6.440, P < 0.001), a significantly longer duration of mechanical ventilation ( Z =-6.082, P < 0.001), and a significantly higher proportion of patients with acute kidney injury, hypoxemia, and pulmonary infection after surgery ( χ 2 =25.661, 25.409, and 20.126, all P < 0.001). The clinical indices with P < 0.1 between the two groups (coronary heart disease, ascites, preoperative levels of albumin/platelets/fibrinogen, time of operation and hepatic portal occlusion, laparotomy, blood loss) were included in the binary logistic regression analysis, and the results showed that time of operation (odds ratio [ OR ]=1.004, 95% confidence interval [ CI ]: 1.002-1.006, P < 0.05) and blood loss ( OR =1.151, 95% CI : 1.009-1.313, P < 0.05) were independent risk factors for hypotension in patients undergoing liver cancer surgery, while preoperative albumin level ( OR =0.950, 95% CI : 0.907-0.995, P < 0.05) was a protective factor. Conclusion There is a relatively high incidence rate of hypotension among severe patients after liver cancer surgery, and a longer time of operation and greater blood loss are independent risk factors for hypotension, while a higher preoperative albumin level is a protective factor.
10.Prognostic evaluation of hip joint function following capsule repair based on a threedimensional finite element analysis model.
Hansheng HU ; Jingcheng WANG ; Zhihua LU ; Weimin FAN
Journal of Southern Medical University 2020;40(12):1826-1830
OBJECTIVE:
To construct a three-dimensional (3D) finite element mechanical model of total hip arthroplasty for comparison of biomechanical differences of the hip joint following capsule repair and postoperative rehabilitation.
METHODS:
Six frozen specimens of hip joint posterior capsule ligament complex were collected in a bone-capsule-bone manner, and the load-strain curve and other mechanical properties of the specimens were tested using a universal material testing machine. Thin-section CT data of the pelvis and lower limbs obtained from a volunteer were imported into Mimics software to construct a 3D model of the hip joint. Digital models of the cup, femoral prosthesis and joint capsule were created in CATIA software and imported into Mimics to simulate total hip arthroplasty; the assembled data were imported into ABAQUS software. The properties of the capsule were set according to results of the mechanical test, anatomical studies, and constitutive equations, and the biomechanics of the anatomically repaired and conventionally repaired capsules were compared during hip flexion.
RESULTS:
The results of testing on the 6 capsule specimens showed a mean ultimate tensile strain of (39.21±5.23)% and a mean of ultimate tensile strength of 1.65±0.38 MPa. The stress-strain curve of the finite element model was consistent with the results of mechanical test on the specimens and the biochemical characteristics of the capsule. The stress was distributed evenly in the anatomically repaired capsule during hip flexion but not in the capsule repaired through the conventional approach; the tensile stress in the lower part of the conventionally repaired capsule reached the ultimate tensile stress measured on the capsule specimens at a 90° flexion.
CONCLUSIONS
The finite element model allows dynamic, quantitative and visual assessment of stress distribution in the hip joint capsule, and compared with the conventional approach, anatomical repair can achieve better biomechanical properties of the capsule.
Arthroplasty, Replacement, Hip
;
Biomechanical Phenomena
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Finite Element Analysis
;
Hip Joint/surgery*
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Humans
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Prognosis
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Stress, Mechanical

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