1.Improvement effect and mechanism of salidroside on radiation-induced parotid gland injury in rats by VIP-cAMP pathway
Chunying ZHANG ; Guangwei YIN ; Hong CHEN ; Mingda YOU ; Jinfeng LIU ; Yakun ZHANG ; Yaojie HU
China Pharmacy 2025;36(22):2796-2801
OBJECTIVE To explore the improvement effect and mechanism of salidroside on radiation-induced parotid gland injury in rats. METHODS Rats were randomly assigned into normal group, radiation group, salidroside low-dose (salidroside-L, 50 mg/kg) group, salidroside high-dose (salidroside-H, 100 mg/kg) group, and salidroside-H+inhibitor (100 mg/kg salidroside+0.1 µmol/kg H-89) group, with 10 rats in each group. Except for the normal group, rats in the other groups were subjected to radiation exposure to establish a model of radiation-induced parotid gland injury. Rats in each group were intraperitoneally injected with the corresponding drug or normal saline, once a day, for 40 consecutive days. After the last administration, the levels of reactive oxygen species (ROS), cyclic adenosine monophosphate (cAMP), superoxide dismutase (SOD), and amylase in serum were detected; the pathological changes of parotid gland tissue were observed; the apoptosis rate of parotid gland tissue cells, the expression levels of B-cell lymphoma-2 (Bcl-2) and its associated X protein (Bax), mRNA expression levels of interleukin-6 (IL- 6) and tumor necrosis factor-α (TNF-α), the protein expression levels of type Ⅲ collagen (Col Ⅲ), vasoactive intestinal peptide (VIP), and the phosphorylation level of protein kinase A (PKA) in parotid gland tissue were determined. RESULTS Compared with normal group, the levels of ROS, amylase, apoptosis rate, Bax expression level, mRNA expression levels of IL-6 and TNF- α, and protein expression level of Col Ⅲ in the radiation group were significantly increased, while the levels of cAMP, SOD, Bcl-2 expression level, VIP protein expression level and PKA phosphorylation level were significantly decreased (P<0.05). Compared with radiation group, the above indicators in the salidroside-L group and salidroside-H group were significantly improved (P<0.05), and the improvement in the salidroside-H group was more significant (P<0.05); inhibitor H-89 significantly reversed the changes in the above indicators of the salidroside-H group (P<0.05). CONCLUSIONS Salidroside can effectively alleviate radiation-induced parotid gland injury in rats, and its mechanism may be related to the activation of the VIP-cAMP pathway.
2.Synthetic MRI for differentiating cervical squamous carcinoma and cervical adenocarcinoma
Jinfeng YIN ; Yong FENG ; Xuezhe WEI ; Junyan GUO ; Minghui LEI ; Wenjuan WANG ; Jingang LIU
Chinese Journal of Medical Imaging Technology 2025;41(1):118-121
Objective To observe the value of synthetic MRI(SyMRI)MAGnetic resonance image Compilation(MAGiC)sequence parameters for differentiating cervical squamous cell carcinoma and cervical adenocarcinoma.Methods Sixty-six patients with pathologically confirmed cervical cancer were retrospectively enrolled and divided into cervical squamous cell carcinoma group(n=56)and cervical adenocarcinoma group(n=10).Quantitative MAGiC parameters were collected and compared between groups,and those being significantly different were combined to construct a logistic regression model.The performance of each parameter alone and their combination for differentiating cervical squamous cell carcinoma and cervical adenocarcinoma was evaluated with receiver operating characteristic(ROC)curve and the area under the curve(AUC).Results In cervical adenocarcinoma group,lesions's T1 and T2 were higher,while R1 and R2 were lower than those in cervical squamous cell carcinoma group(all P<0.05).No statistically significant difference of proton density was found between groups(P>0.05).The AUC of T1,T2,R1,R2 alone and their combination for differentiating cervical squamous cell carcinoma and cervical adenocarcinoma was 0.959,0.945,0.961,0.942 and 0.996,respectively,and no significant difference was found between each two ones(Z=0.267 to 1.396,all P>0.05).Conclusion SyMRI had high value for differentiating cervical squamous cell carcinoma and cervical adenocarcinoma.
3.Proteomic analysis of serum proteins in mice with carbapenem-resistant hypervirulent Klebsiella pneumoniae bloodstream infection
Jinfeng BAO ; Yating MA ; Yin XU ; Yanjuan HE ; Yuyue WANG ; Luoluo SHI ; Chengbin WANG
Chinese Journal of Nosocomiology 2025;35(6):823-828
OBJECTIVE To observe the changes of serum proteins in the mice with carbapenem-resistant hyperviru-lent Klebsiella pneumoniae(CR-hvKP)bloodstream infection by using liquid chromatogram-mass spectrometer(LC-MS),find out the differentially expressed proteins and carry out corresponding biological function analysis.METHODS The models of ICR mice with CR-hvKP and classical Klebsiella pneumoniae(cKP)bloodstream infec-tions were established,the serum specimens were collected from the mice at 12 hours of establishment of the in-fection models and were detected by using LC-MS.The result of LC-MS was identified by using Maxquant soft-ware.The corresponding bioinformatics analysis was performed for the differentially expressed proteins.RESULTS As compared with the normal control group,there were 24 upregulated proteins and 20 downregulated proteins in CR-hvKP group.As compared with cKP group,there were 107 upregulated proteins in the CR-hvKP group.The 134 differentially expressed proteins were retrieved one by one from Uniprot database,it was found that the pro-teins were involved in biological regulation,immune process,biological interaction,movement,metabolic process,response to stimulation,signal transduction,inflammatory response,oxidative stress and angiogenesis.The signal pathway analysis involved multiple metabolism-related pathways,including complement and coagula-tion cascades,cholesterol metabolism,bacterial infection,heme clearance,and assembly,remodeling and clear-ance of plasma lipoprotein.In terms of the proteins being attached great importance,the expression levels of kal-likrein B1(KLKB1)and serpin family A(Serpina)1b were downregulated as compared with the normal control group and were upregulated as compared with the cKP group;the expression levels of serum amyloid A protein(SAA)1,SAA2,Vanin-3(VNN3)and hemoglobinβpolypeptide chain b2(HBB-b2)were upregulated as com-pared with both the cKP group and the normal control group.CONCLUSIONS The CR-hvKP bloodstream infection involves the activation and action of multiple proteins.The rise of SAA1,SAA2,VNN3 and HBB-b2 or the de-cline of KLKB1 and Serpina1b may indicate the CR-hvKP bloodstream infection.
4.The impact of coexisting choroidal detachment on surgical prognosis in macular hole retinal detachment associated with high myopia
Yi CAI ; Mingwei ZHAO ; Jianhong LIANG ; Hong YIN ; Wenzhen YU ; Xuan SHI ; Jinfeng QU ; Yong CHENG ; Jing HOU ; Heng MIAO ; Enzhong JIN
Chinese Journal of Ocular Fundus Diseases 2025;41(2):89-97
Objective:To investigate the clinical characteristics of patients with high-myopia macular hole retinal detachment (MHRD) combined with choroidal detachment and to preliminarily analyze factors associated with postoperative hole closure.Methods:A retrospective clinical case series study. A total of 68 patients with high myopia (68 eyes) with MHRD diagnosed by Department of Ophthalmology, Peking University People’s Hospital from January 2019 to April 2024 were included in this study. Among them, there were 14 males (14 eyes) and 54 females (54 eyes). The mean age was (61.10±9.66) years. All eyes were treated with pars plana vitrectomy (PPV) combined with silicone oil or gas filling. Best corrected visual acuity (BCVA), intraocular pressure, and B-mode ultrasonography were performed. The BCVA test was performed using the Snellen visual acuity chart, which was statistically converted to logarithm of the minimum angle of resolution (logMAR) visual acuity. The range of choroidal detachment was defined according to the number of involved quadrants observed in B-mode ultrasound or surgery, which was divided into 1 to 4 quadrants. Axial length (AL) was measured under retinal reattachment. In 68 eyes, there were 17 eyes with choroidal detachment and 51 eyes without choroidal detachment, respectively. There were 17 eyes with choroidal detachment, and the detachment range involved 1, 2, 2 and 12 eyes in 1, 2, 3 and 4 quadrants, respectively. During operation, 13% C 3F 8 was filled in 2 eyes, all of which were not complicated with choroidal detachment. 66 eyes were filled with silicone oil. According to whether the patients were complicated with choroidal detachment, the patients were divided into the group without choroidal detachment and the group with choroidal detachment. Independent sample t test, Welch two-sample t test or Mann-Whitney U test were used for comparison between groups. Generalized linear regression and logistic regression were used to analyze the relationship between the aperture size of postoperative unclosed holes and the closed hole after surgery and clinical factors. Results:At 3 months after surgery, the logMAR BCVA of the affected eye was 1.29±0.43, with a preoperative to postoperative difference ranging from -1.60 to 0.70 (-0.51±0.51) logMAR units. The AL ranged from 26.6 to 34.3 (29.60±2.12) mm. Among 68 eyes, macular hole of 37 (54.4%, 37/68) eyes were open and 31 (45.6%, 31/68) eyes were closed, respectively. The hole diameter of the open eye was (753±424) μm. There was no significant difference in age, course of disease and AL between the two groups ( W=412.0, 477.5, 427.0; P>0.05). Before operation, BCVA in patients with choroidal detachment was worse ( W=257.5) and intraocular pressure was lower ( t=4.051) in patients with choroidal detachment compared with those without choroidal detachment, with statistical significance ( P<0.05). At 3 months after surgery, BCVA in patients with choroidal detachment was significantly worse than that in patients without choroidal detachment, with statistical significance ( W=284.0, P<0.05). There were no significant differences in logMAR BCVA difference ( t=0.616) and macular hole closure rate ( χ 2=0.000) before and after surgery ( P>0.05). The reoperation rate of retinal detachment due to persistent or recurrent retinal detachment was significantly higher in the group with choroid detachment than in the group without choroid detachment, and the difference was statistically significant (odds ratio=6.424, P<0.05). Logistic regression analysis showed that young age was significantly correlated with macular hole closure failure after surgery ( β=0.077, P=0.015). There was no correlation between AL, duration of disease, BCVA before surgery, intraocular pressure, wether combined with choroid detachment range and postoperative hole closure ( β=-0.072, 0.000, 0.672, -0.085, -0.391; P>0.05). Conclusions:Concomitant choroidal detachment adversely affected on both pre-operative and post-operative visual acuity in high myopia MHRD. It is closely associated with the risk of recurrent retinal detachment and the needs of multiple operations, but has no significant effect on hole closure rate. Lower age of onset may be a risk factor for macular hole closure.
5.Clinical analysis of the correlation between ectopic inner foveal layer with idiopathic epiretinal membrane and prognosis after pars plana vitrectomy
Jiyang TANG ; Jinfeng QU ; Xuan SHI ; Huijun QI ; Tong QIAN ; Wenzhen YU ; Hong YIN ; Jing HOU ; Yong CHENG ; Jianhong LIANG ; Mingwei ZHAO ; Xiaoxin LI ; Heng MIAO ; Yaoyao SUN
Chinese Journal of Ocular Fundus Diseases 2025;41(8):586-594
Objective:To observe and analyze the correlation between ectopic foveal inner layer (EIFL) and the EIFL-based idiopathic epiretinal membrane (ERM) staging system and the anatomic and functional prognosis of ERM eyes post pars plana vitrectomy (PPV).Methods:A retrospective study. From January 1, 2020 to October 30, 2023, 345 eyes of 330 patients diagnosed with idiopathic ERM in Department of Ophthalmology of Peking University People's Hospital and treated with standard transciliary flat three-channel 25G PPV combined with ERM and internal limiting membrane exfoliation were included in the study. Among them, 96 were males (111 eyes) and 234 were females (234 eyes). The mean age was (66.8±7.7) years. All study eyes received standard three-port 25G PPV combined with ERM and internal limiting membrane peeling. All study eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. BCVA was performed using a standard logarithmic visual acuity chart and converted to logarithm of the minimum angle of resolution visual acuity for statistical analysis. EIFL thickness and central foveal thickness (CFT) on OCT were measured. ERM eyes were grouped into stage Ⅰ, Ⅱ, Ⅲ and Ⅳ according to ERM staging scheme based on EIFL; disorganization of the retinal inner layers (DRIL) of study eyes were assessed and grouped into no, mild and severe groups. The correlation between ERM staging as well as EIFL thickness and the anatomical and functional prognosis 6 months post-PPV were analyzed.Results:Among 345 study eyes, 12, 87, 174 and 72 eyes were stage Ⅰ-Ⅳ ERM respectively, 63 with no DRIL, 216 with mild DRIL and 66 with severe DRIL. Among the 153 eyes with macular edema, the edema subsided in 66 eyes (43.1%, 66/153) 6 months after the operation. Eighty-seven eyes (56.9%, 87/153) did not regress. The edema subsided 6 months after the operation was not significantly correlated with the ERM stage before the operation ( χ2=3.331, R=?0.145, P=0.304) or the degree of DRIL ( χ2=0.655, R=?0.108, P=0.445). The results of the correlation analysis showed that logMAR BCVA 6 months after the surgery was positively correlated with the degree of DRIL before the surgery ( Tau-b=0.236), ERM stage ( Tau-b=0.194), CFT ( r=0.383), and EIFL thickness ( r=0.317) ( P<0.05). There was no significant correlation with the thickness of the outer nuclear layer before the operation ( r=0.004, P>0.05). Preoperative ERM stage ( Tau-b=0.303, P<0.001) and DRIL severity ( Tau-b= 0.238, P=0.001) were positively correlated with CFT at 6 months after surgery. Conclusion:The ERM stage and EIFL thickness before the operation are positively correlated with logMAR BCVA and CFT 6 months after the operation.
6.The impact of coexisting choroidal detachment on surgical prognosis in macular hole retinal detachment associated with high myopia
Yi CAI ; Mingwei ZHAO ; Jianhong LIANG ; Hong YIN ; Wenzhen YU ; Xuan SHI ; Jinfeng QU ; Yong CHENG ; Jing HOU ; Heng MIAO ; Enzhong JIN
Chinese Journal of Ocular Fundus Diseases 2025;41(2):89-97
Objective:To investigate the clinical characteristics of patients with high-myopia macular hole retinal detachment (MHRD) combined with choroidal detachment and to preliminarily analyze factors associated with postoperative hole closure.Methods:A retrospective clinical case series study. A total of 68 patients with high myopia (68 eyes) with MHRD diagnosed by Department of Ophthalmology, Peking University People’s Hospital from January 2019 to April 2024 were included in this study. Among them, there were 14 males (14 eyes) and 54 females (54 eyes). The mean age was (61.10±9.66) years. All eyes were treated with pars plana vitrectomy (PPV) combined with silicone oil or gas filling. Best corrected visual acuity (BCVA), intraocular pressure, and B-mode ultrasonography were performed. The BCVA test was performed using the Snellen visual acuity chart, which was statistically converted to logarithm of the minimum angle of resolution (logMAR) visual acuity. The range of choroidal detachment was defined according to the number of involved quadrants observed in B-mode ultrasound or surgery, which was divided into 1 to 4 quadrants. Axial length (AL) was measured under retinal reattachment. In 68 eyes, there were 17 eyes with choroidal detachment and 51 eyes without choroidal detachment, respectively. There were 17 eyes with choroidal detachment, and the detachment range involved 1, 2, 2 and 12 eyes in 1, 2, 3 and 4 quadrants, respectively. During operation, 13% C 3F 8 was filled in 2 eyes, all of which were not complicated with choroidal detachment. 66 eyes were filled with silicone oil. According to whether the patients were complicated with choroidal detachment, the patients were divided into the group without choroidal detachment and the group with choroidal detachment. Independent sample t test, Welch two-sample t test or Mann-Whitney U test were used for comparison between groups. Generalized linear regression and logistic regression were used to analyze the relationship between the aperture size of postoperative unclosed holes and the closed hole after surgery and clinical factors. Results:At 3 months after surgery, the logMAR BCVA of the affected eye was 1.29±0.43, with a preoperative to postoperative difference ranging from -1.60 to 0.70 (-0.51±0.51) logMAR units. The AL ranged from 26.6 to 34.3 (29.60±2.12) mm. Among 68 eyes, macular hole of 37 (54.4%, 37/68) eyes were open and 31 (45.6%, 31/68) eyes were closed, respectively. The hole diameter of the open eye was (753±424) μm. There was no significant difference in age, course of disease and AL between the two groups ( W=412.0, 477.5, 427.0; P>0.05). Before operation, BCVA in patients with choroidal detachment was worse ( W=257.5) and intraocular pressure was lower ( t=4.051) in patients with choroidal detachment compared with those without choroidal detachment, with statistical significance ( P<0.05). At 3 months after surgery, BCVA in patients with choroidal detachment was significantly worse than that in patients without choroidal detachment, with statistical significance ( W=284.0, P<0.05). There were no significant differences in logMAR BCVA difference ( t=0.616) and macular hole closure rate ( χ 2=0.000) before and after surgery ( P>0.05). The reoperation rate of retinal detachment due to persistent or recurrent retinal detachment was significantly higher in the group with choroid detachment than in the group without choroid detachment, and the difference was statistically significant (odds ratio=6.424, P<0.05). Logistic regression analysis showed that young age was significantly correlated with macular hole closure failure after surgery ( β=0.077, P=0.015). There was no correlation between AL, duration of disease, BCVA before surgery, intraocular pressure, wether combined with choroid detachment range and postoperative hole closure ( β=-0.072, 0.000, 0.672, -0.085, -0.391; P>0.05). Conclusions:Concomitant choroidal detachment adversely affected on both pre-operative and post-operative visual acuity in high myopia MHRD. It is closely associated with the risk of recurrent retinal detachment and the needs of multiple operations, but has no significant effect on hole closure rate. Lower age of onset may be a risk factor for macular hole closure.
7.Clinical analysis of the correlation between ectopic inner foveal layer with idiopathic epiretinal membrane and prognosis after pars plana vitrectomy
Jiyang TANG ; Jinfeng QU ; Xuan SHI ; Huijun QI ; Tong QIAN ; Wenzhen YU ; Hong YIN ; Jing HOU ; Yong CHENG ; Jianhong LIANG ; Mingwei ZHAO ; Xiaoxin LI ; Heng MIAO ; Yaoyao SUN
Chinese Journal of Ocular Fundus Diseases 2025;41(8):586-594
Objective:To observe and analyze the correlation between ectopic foveal inner layer (EIFL) and the EIFL-based idiopathic epiretinal membrane (ERM) staging system and the anatomic and functional prognosis of ERM eyes post pars plana vitrectomy (PPV).Methods:A retrospective study. From January 1, 2020 to October 30, 2023, 345 eyes of 330 patients diagnosed with idiopathic ERM in Department of Ophthalmology of Peking University People's Hospital and treated with standard transciliary flat three-channel 25G PPV combined with ERM and internal limiting membrane exfoliation were included in the study. Among them, 96 were males (111 eyes) and 234 were females (234 eyes). The mean age was (66.8±7.7) years. All study eyes received standard three-port 25G PPV combined with ERM and internal limiting membrane peeling. All study eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. BCVA was performed using a standard logarithmic visual acuity chart and converted to logarithm of the minimum angle of resolution visual acuity for statistical analysis. EIFL thickness and central foveal thickness (CFT) on OCT were measured. ERM eyes were grouped into stage Ⅰ, Ⅱ, Ⅲ and Ⅳ according to ERM staging scheme based on EIFL; disorganization of the retinal inner layers (DRIL) of study eyes were assessed and grouped into no, mild and severe groups. The correlation between ERM staging as well as EIFL thickness and the anatomical and functional prognosis 6 months post-PPV were analyzed.Results:Among 345 study eyes, 12, 87, 174 and 72 eyes were stage Ⅰ-Ⅳ ERM respectively, 63 with no DRIL, 216 with mild DRIL and 66 with severe DRIL. Among the 153 eyes with macular edema, the edema subsided in 66 eyes (43.1%, 66/153) 6 months after the operation. Eighty-seven eyes (56.9%, 87/153) did not regress. The edema subsided 6 months after the operation was not significantly correlated with the ERM stage before the operation ( χ2=3.331, R=?0.145, P=0.304) or the degree of DRIL ( χ2=0.655, R=?0.108, P=0.445). The results of the correlation analysis showed that logMAR BCVA 6 months after the surgery was positively correlated with the degree of DRIL before the surgery ( Tau-b=0.236), ERM stage ( Tau-b=0.194), CFT ( r=0.383), and EIFL thickness ( r=0.317) ( P<0.05). There was no significant correlation with the thickness of the outer nuclear layer before the operation ( r=0.004, P>0.05). Preoperative ERM stage ( Tau-b=0.303, P<0.001) and DRIL severity ( Tau-b= 0.238, P=0.001) were positively correlated with CFT at 6 months after surgery. Conclusion:The ERM stage and EIFL thickness before the operation are positively correlated with logMAR BCVA and CFT 6 months after the operation.
8.Proteomic analysis of serum proteins in mice with carbapenem-resistant hypervirulent Klebsiella pneumoniae bloodstream infection
Jinfeng BAO ; Yating MA ; Yin XU ; Yanjuan HE ; Yuyue WANG ; Luoluo SHI ; Chengbin WANG
Chinese Journal of Nosocomiology 2025;35(6):823-828
OBJECTIVE To observe the changes of serum proteins in the mice with carbapenem-resistant hyperviru-lent Klebsiella pneumoniae(CR-hvKP)bloodstream infection by using liquid chromatogram-mass spectrometer(LC-MS),find out the differentially expressed proteins and carry out corresponding biological function analysis.METHODS The models of ICR mice with CR-hvKP and classical Klebsiella pneumoniae(cKP)bloodstream infec-tions were established,the serum specimens were collected from the mice at 12 hours of establishment of the in-fection models and were detected by using LC-MS.The result of LC-MS was identified by using Maxquant soft-ware.The corresponding bioinformatics analysis was performed for the differentially expressed proteins.RESULTS As compared with the normal control group,there were 24 upregulated proteins and 20 downregulated proteins in CR-hvKP group.As compared with cKP group,there were 107 upregulated proteins in the CR-hvKP group.The 134 differentially expressed proteins were retrieved one by one from Uniprot database,it was found that the pro-teins were involved in biological regulation,immune process,biological interaction,movement,metabolic process,response to stimulation,signal transduction,inflammatory response,oxidative stress and angiogenesis.The signal pathway analysis involved multiple metabolism-related pathways,including complement and coagula-tion cascades,cholesterol metabolism,bacterial infection,heme clearance,and assembly,remodeling and clear-ance of plasma lipoprotein.In terms of the proteins being attached great importance,the expression levels of kal-likrein B1(KLKB1)and serpin family A(Serpina)1b were downregulated as compared with the normal control group and were upregulated as compared with the cKP group;the expression levels of serum amyloid A protein(SAA)1,SAA2,Vanin-3(VNN3)and hemoglobinβpolypeptide chain b2(HBB-b2)were upregulated as com-pared with both the cKP group and the normal control group.CONCLUSIONS The CR-hvKP bloodstream infection involves the activation and action of multiple proteins.The rise of SAA1,SAA2,VNN3 and HBB-b2 or the de-cline of KLKB1 and Serpina1b may indicate the CR-hvKP bloodstream infection.
9.Synthetic MRI for differentiating cervical squamous carcinoma and cervical adenocarcinoma
Jinfeng YIN ; Yong FENG ; Xuezhe WEI ; Junyan GUO ; Minghui LEI ; Wenjuan WANG ; Jingang LIU
Chinese Journal of Medical Imaging Technology 2025;41(1):118-121
Objective To observe the value of synthetic MRI(SyMRI)MAGnetic resonance image Compilation(MAGiC)sequence parameters for differentiating cervical squamous cell carcinoma and cervical adenocarcinoma.Methods Sixty-six patients with pathologically confirmed cervical cancer were retrospectively enrolled and divided into cervical squamous cell carcinoma group(n=56)and cervical adenocarcinoma group(n=10).Quantitative MAGiC parameters were collected and compared between groups,and those being significantly different were combined to construct a logistic regression model.The performance of each parameter alone and their combination for differentiating cervical squamous cell carcinoma and cervical adenocarcinoma was evaluated with receiver operating characteristic(ROC)curve and the area under the curve(AUC).Results In cervical adenocarcinoma group,lesions's T1 and T2 were higher,while R1 and R2 were lower than those in cervical squamous cell carcinoma group(all P<0.05).No statistically significant difference of proton density was found between groups(P>0.05).The AUC of T1,T2,R1,R2 alone and their combination for differentiating cervical squamous cell carcinoma and cervical adenocarcinoma was 0.959,0.945,0.961,0.942 and 0.996,respectively,and no significant difference was found between each two ones(Z=0.267 to 1.396,all P>0.05).Conclusion SyMRI had high value for differentiating cervical squamous cell carcinoma and cervical adenocarcinoma.
10.PTHrP participates in the bone destruction of middle ear cholesteatoma via promoting macrophage differentiation into osteoclasts induced by RANKL
Shumin XIE ; Li JIN ; Jinfeng FU ; Qiulin YUAN ; Tuanfang YIN ; Jihao REN ; Wei LIU
Journal of Central South University(Medical Sciences) 2024;49(5):655-666
Objective:Progressive bone resorption and destruction is one of the most critical clinical features of middle ear cholesteatoma,potentially leading to various intracranial and extracranial complications.However,the mechanisms underlying bone destruction in middle ear cholesteatoma remain unclear.This study aims to explore the role of parathyroid hormone-related protein(PTHrP)in bone destruction associated with middle ear cholesteatoma. Methods:A total of 25 cholesteatoma specimens and 13 normal external auditory canal skin specimens were collected from patients with acquired middle ear cholesteatoma.Immunohistochemical staining was used to detect the expressions of PTHrP,receptor activator for nuclear factor-kappa B ligand(RANKL),and osteoprotegerin(OPG)in cholesteatoma and normal tissues.Tartrate-resistant acid phosphatase(TRAP)staining was used to detect the presence of TRAP positive multi-nucleated macrophages in cholesteatoma and normal tissues.Mono-nuclear macrophage RAW264.7 cells were subjected to interventions,divided into a RANKL intervention group and a PTHrP+RANKL co-intervention group.TRAP staining was used to detect osteoclast formation in the 2 groups.The mRNA expression levels of osteoclast-related genes,including TRAP,cathepsin K(CTSK),and nuclear factor of activated T cell cytoplasmic 1(NFATc1),were measured using real-time polymerase chain reaction(real-time PCR)after the interventions.Bone resorption function of osteoclasts was assessed using a bone resorption pit analysis. Results:Immunohistochemical staining showed significantly increased expression of PTHrP and RANKL and decreased expression of OPG in cholesteatoma tissues(all P<0.05).PTHrP expression was significantly positively correlated with RANKL,the RANKL/OPG ratio,and negatively correlated with OPG expression(r=0.385,r=0.417,r=-0.316,all P<0.05).Additionally,the expression levels of PTHrP and RANKL were significantly positively correlated with the degree of bone destruction in cholesteatoma(r=0.413,r=0.505,both P<0.05).TRAP staining revealed a large number of TRAP-positive cells,including multi-nucleated osteoclasts with three or more nuclei,in the stroma surrounding the cholesteatoma epithelium.After 5 days of RANKL or PTHrP+RANKL co-intervention,the number of osteoclasts was significantly greater in the PTHrP+RANKL co-intervention group than that in the RANKL group(P<0.05),with increased mRNA expression levels of TRAP,CTSK,and NFATc1(all P<0.05).Scanning electron microscopy of bone resorption pits showed that the number(P<0.05)and size of bone resorption pits on bone slices were significantly greater in the PTHrP+RANKL co-intervention group compared with the RANKL group. Conclusion:PTHrP may promote the differentiation of macrophages in the surrounding stroma of cholesteatoma into osteoclasts through RANKL induction,contributing to bone destruction in middle ear cholesteatoma.

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