Objective:This study aims to investigate the therapeutic efficacy of staged endoscopic surgery for Shin-Ⅲ stage external auditory canal cholesteatoma. Methods:A retrospective analysis was conducted on the clinical data of 25 patients diagnosed with Shin-Ⅲ cholesteatoma of the external auditory canal, who were admitted to the Otology Center of the First People's Hospital of Foshan City from May 2020 to October 2024. All patients initially underwent endoscopic cholesteatoma removal. Based on the outcomes of the first-stage postoperative follow-up, patients were categorized into two groups: the repair type and the non-repair type. The non-repair type was further subdivided into simple and complex types. Of the total cases, 10 patients were of the repair type, with 9 requiring no further surgical intervention. The non-repair type comprised 15 patients, of which 8 were classified as simple type and underwent either tympanoplasty type Ⅰ or external auditory canal wall reconstruction during the second stage. The remaining 7 patients, identified as complex type, received open mastoidectomy or tympanotomy in the second stage, with or without ossicular chain reconstruction. Results:All patients were monitored for a minimum of six months postoperatively. The incidence of dry ear was observed in 22 patients, corresponding to a dry ear rate of 88.0%. Four cases experienced primary complications. Conclusion:Endoscopic phased operation for managing Shin-Ⅲ stage cholesteatoma of the external auditory canal can ensure that the surgical options match the severity of the lesions, reducing unnecessary surgical trauma and achieving good efficacy.
Humans ; Retrospective Studies ; Ear Canal/surgery* ; Endoscopy/methods* ; Cholesteatoma/surgery* ; Male ; Tympanoplasty ; Female ; Treatment Outcome ; Adult ; Middle Aged ; Cholesteatoma, Middle Ear/surgery* ; Mastoidectomy

OBJECTIVE To explore the effect and mechanism of Zhiqiao gancao decoction （ZQGCD） on pathological angiogenesis of degenerative intervertebral disc. METHODS The rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， hypoxia inducible factor-1α （HIF-1α） inhibitor （YC-1） group [2 mg/（kg·d）， tail vein injection]， and ZQGCD low-dose， medium-dose and high-dose groups [3.06， 6.12， 12.24 g/（kg·d）]， with 8 rats in each group. Except for sham operation group， lumbar disc degeneration model of rat was constructed in all other groups. After modeling， they were given relevant medicine once a day， for consecutive 3 weeks. After the last medication， pathological changes and angiogenesis of the intervertebral disc tissue in rats were observed； the levels of inflammatory factors [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] and the expressions of angiogenesis-related proteins [HIF-1α， vascular endothelial growth factor （VEGF）， VEGF receptor 2 （VEGFR2）， angiotensin 1（Ang 1）， Ang 2] in the com intervertebral disc tissue in rats were all determined. In cell experiment， the primary nucleus pulposus cells were isolated and cultured from rats， and cellular degeneration was induced using 50 ng/mL TNF-α. The cells were divided into blank control group （10% blank control serum）， TNF-α group （10% blank control serum）， YC-1 group （10% blank control serum+0.2 mmol/L YC-1）， and 5%， 10%， 15% drug-containing serum group （5%， 10%， 15% drug-containing serum）. After 24 hours of intervention， the nucleus pulposus cells were co-cultured with HUVEC. The expressions of Collagen Ⅱ， matrix metalloproteinase-3 （MMP-3） in nucleus pulposus cells were detected. HUVEC proliferation， migration and tube forming ability were detected， and the expression levels of the HIF-1α/VEGF/Ang signal axis and angiogenesis- related proteins （add MMP-2， MMP-9） in HUVEC were detected. RESULTS Animal experiments had shown that compared with model group， the positive expression of CD31 in the intervertebral disc tissues of rats in each drug group was down-regulated （P＜ 0.05）， the levels of inflammatory factors and angiogenesis-related proteins were decreased significantly （P＜0.05）， and the pathological changes in the intervertebral disc were alleviated. Cell experiments had shown that compared with TNF-α group， the expression of Collagen Ⅱ in nucleus pulposus cells of all drug groups was significantly up-regulated （P＜0.05）， and the expression of MMP-3 was significantly down-regulated （P＜0.05）； the proliferation， migration and tubulogenesis of HUVEC were significantly weakened （P＜0.05）. The mRNA and protein expressions of HIF-1α， VEGF， Ang 2 as well as the expression of angiogenesis-related proteins （except for the expression of Ang 2 mRNA and HIF-1α， VEGFR2， Ang 2 protein in 5% drug- containing serum group） were significantly down-regulated （P＜0.05）. CONCLUSIONS ZQGCD may inhibit the HIF-1α/VEGF/ Ang signal axis to weaken the angiogenic ability of vascular endothelial cells， improve pathological angiogenesis in the intervertebral disc， and delay the degeneration of the intervertebral disc.

Objective:To establish a prognostic model based on endoplasmic reticulum stress-related genes for evaluating the prognosis of patients with renal cell carcinoma.Methods:This study utilized Non-negative Matrix Factorization to identify molecular subgroups based on endoplasmic reticulum stress-related genes and employed Weighted Correlation Network Analysis to determine co-expressed genes associ-ated with these subgroups.A risk prognostic model was constructed using univariate Cox regression analysis and Lasso regression analysis.Preliminary experimental validations were conducted to elucidate the biological functions of model genes in renal cell carcinoma.Results:Two molecular subgroups with distinct survival prognoses were identified,and an intersection of related genes was used to construct a nov-el endoplasmic reticulum stress-related prognostic model.Patients in the high-risk group exhibited significantly poorer overall survival in both the training and validation cohorts.In vivo experiments demonstrated that PCK1,a model gene,could inhibit the proliferation,migra-tion,and invasion of renal cell carcinoma cells.Conclusions:The risk scoring model developed in this study effectively predicts the survival probability of renal cell carcinoma patients and can serve as an independent prognostic indicator.This model offers a new direction for per-sonalized treatment strategies in renal cell carcinoma patients.

ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

Objective:To evaluate the clinical effect of different types of aortic root replacement in adolescent patients with aortic root aneurysm by analyzing the perioperative and follow-up conditions of surgical treatment for adolescent aortic root aneurysm.Methods:The clinical data of patients aged ≤18 years who were admitted to the Beijing Anzhen Hospital from November 2012 to February 2025, diagnosed with aortic root aneurysm by ultrasound or aortic computed tomography angiography (CTA) and requiring surgical intervention, were collected retrospectively. They were divided into the valve-sparing aortic root replacement group (David operation group) and the aortic root replacement group (Bentall operation group) according to the surgical method. The perioperative results and long-term follow-up results of the two groups were analyzed. Kaplan-Meier survival curves were drawn to compare the reoperation intervention rate between the two groups.Results:A total of 25 patients were included in this study, including 17 in the Bentall group and 8 in the David group. There were no statistically significant differences in gender, age, blood routine, liver and kidney function, coagulation function, and electrolyte internal environment between the two groups (all P>0.05). There were no statistically significant differences in operation time and intensive care unit stay between the two groups (all P>0.05). Compared with the Bentall operation group, the intraoperative blood loss in the David operation group was more ( P<0.05). During the follow-up, no reoperation occurred in the Bentall operation group, while 3 patients in the David operation group had long-term re-intervention. The long-term reoperation intervention rate in the David operation group was higher than that in the Bentall group ( P=0.042), but there was no statistically significant difference in the aortic valve-related surgical intervention rate between the two groups ( P=0.15). Conclusions:For adolescent patients with aortic root aneurysm, although David operation may face long-term reoperation intervention, this intervention may not be due to the difference in surgical methods. Both Bentall operation and David operation are safe and reliable, with good perioperative results and stable medium and long-term prognosis.

Objective To assess the efficacy of clear lens extraction combined with extended depth of focus(EDOF)intraocular lens(IOL)implantation in enhancing visual quality and concurrently opening peripheral angle structures in patients diagnosed with primary angle closure suspect(PACS)and presbyopia.Methods A total of 80 patients with PACS,presbyopia,and transparent lenses were enrolled and divided into two groups based on the type of implanted lens:a control group(n=46)and an experimental group(n=34).The control group underwent clear lens extraction followed by monofocal intraocular lens implantation,while the experimental group underwent clear lens extraction followed by extended depth of focus(EDOF)intraocular lens implantation.Preoperative and postoperative evaluations at 3 months included visual acuity,intraocular pressure,anterior segment structure,defocus curve,and Catquest 9SF-CN questionnaire scores.Adverse events were recorded to assess safety.Results Regarding the angular structure,after 3 months of treatment,results indicated significant increases in central ante-rior chamber depth,angle opening distance at 750 μ m,angle recess area at 750 μ m,trabecular-iris space area at 750 μm,and trabecular-iris angle at 750 μm in both groups compared to preoperative values(all P<0.01).However,no significant differences were observed between the two groups(all P>0.05).For the defocusing curve,visual acuity in the experimental group improved from+1.0 D to-4.0 D after 3 months of treatment(all P<0.05),while the control group showed improvements at+0.5 D,-0.5 D,-1.0 D,-2.0 D,-3.0 D,-3.5 D,and-4.0 D(all P<0.05).Postoperatively at 3 months,the experimental group exhibited superior visual acuity to the control group at-1.0 D to-4.0 D(all P<0.05).According to the Catquest 9SF-CN scale,scores in both groups significantly im-proved after 3 months of treatment(P<0.01),with the experimental group scoring higher than the control group(P<0.01).During the study,transient intraocular pressure elevation occurred in 7 patients(3 in the control group and 4 in the experimental group),but no serious adverse reactions were reported in either group.Conclusions In patients with pseudoexfoliation glaucoma combined with presbyopia,significant improvements in angle structures were observed following clear lens extraction.The implantation of an EDOF IOL notably enhanced postoperative visual quality compared to monofocal IOLs.

Objective To investigate the efficiency and mechanism of C1q tumor necrosis factor-related protein 3(CTRP3)on reprogramming of cardiac fibroblasts(CFs)into induced cardiomyocyte-like cells(iCMs)by Sendai virus(SeV)vector overexpressing Gata4,Mef2c and Tbx5(SeVGMT).Methods CFs were divided into Control,NC-Lv,CTRP3-Lv,NC-sh,and CTRP3-sh groups.NC-Lv,CTRP3-Lv,NC-sh,and CTRP3-sh were transfected into CFs using Lipofectamine 3000 reagent for 48 hours.Lipofectamine 3000 reagent was then mixed with SeVGMT and incubated at room temperature for 48 hours,the culture medium was then replaced,and cells were cultured for 21 days.Cell morphology was observed under a microscope at 0,3,7,14,and 21 days.Expression levels of the myocardial-specific proteins α-myosin heavy chain(α-MHC),α-actin,cardiac troponin T(cTnT),connexin 43(Cx43),cardiac muscle α-actin(Actc1),and myosin heavy chain 6(Myh6)were detected at different time points by immunofluorescence,quantitative reverse transcription-polymerase chain reaction,and Western blot,and the proportions of beating cells at different time points were calculated.Results The relative fluorescence intensity and mRNA and protein levels of α-MHC,α-actin,cTnT,Cx43,Actc1,and Myh6 in CFs in each group increased with increasing culture time(P＜0.05),with significantly higher expression levels of myocardial-specific proteins at 14 days of culture than at 7 days(P＜0.05).The relative fluorescence intensities and mRNA and protein levels of α-MHC,α-actin,cTnT,Cx43,Actc1,and Myh6 in CFs at 3,7,14,and 21 days of culture were significantly increased in the CTRP3-Lv group compared with the NC-Lv group(P＜0.05),but were significantly decreased in CFs in the CTRP3-sh group compared with the NC-sh group(P＜0.05).Beating cells appeared in CFs in each group at 7 days of culture.The proportion of beating cells in each group increased with increasing culture time(P＜0.05),and the proportion was significantly higher at 14 days than at 7 days(P＜0.05).The proportion of beating cells among CFs was increased in the CTRP3-Lv group at 7,14,and 21 days of culture compared with the NC-Lv group(P＜0.05),while the proportion of beating cells in the CTRP3-sh group was decreased compared with the NC-sh group(P＜0.05).Conclusions CTRP3 can enhance SeVGMT reprogramming of CFs into iCMs.

Objective To analyze the causal association of telomere length with prostate cancer in East Asian and European popula-tions using Mendelian randomization.Methods Using published genome-wide association data,single nucleotide polymorphisms signif-icantly associated with telomere length were screened as instrumental variables.The primary research method was Mendelian randomization analysis using a random effects model with inverse variance weighted method.Complementary analyses were also performed using Mende-lian randomization-Egger method,weighted median method,simple model and weighted model methods to explore the causal relationship between telomere length and prostate cancer.In addition,the robustness of the results was assessed by sensitivity analyses.Results The results of the inverse variance weighted method analysis showed a positive causal relationship between genetically predicted telomere length and prostate cancer risk in East Asian(OR=1.420,95％CI:1.149-1.755,P=0.001)and European populations(OR=1.358,95％CI:1.242-1.484,P=1.727 × 10-11).The results of the remaining four analyses showed statistical significance(P＜0.05),and the odds ratio was in the same direction as that of the inverse variance weighted method.Sensitivity analyses also showed the robustness of the results.Conclusion Individuals with genetically predicted longer telomere length may be at increased risk of developing prostate cancer in East Asian and European populations.

Objective To analyze the causal association of telomere length with prostate cancer in East Asian and European popula-tions using Mendelian randomization.Methods Using published genome-wide association data,single nucleotide polymorphisms signif-icantly associated with telomere length were screened as instrumental variables.The primary research method was Mendelian randomization analysis using a random effects model with inverse variance weighted method.Complementary analyses were also performed using Mende-lian randomization-Egger method,weighted median method,simple model and weighted model methods to explore the causal relationship between telomere length and prostate cancer.In addition,the robustness of the results was assessed by sensitivity analyses.Results The results of the inverse variance weighted method analysis showed a positive causal relationship between genetically predicted telomere length and prostate cancer risk in East Asian(OR=1.420,95％CI:1.149-1.755,P=0.001)and European populations(OR=1.358,95％CI:1.242-1.484,P=1.727 × 10-11).The results of the remaining four analyses showed statistical significance(P＜0.05),and the odds ratio was in the same direction as that of the inverse variance weighted method.Sensitivity analyses also showed the robustness of the results.Conclusion Individuals with genetically predicted longer telomere length may be at increased risk of developing prostate cancer in East Asian and European populations.

Objective:To evaluate the clinical effect of different types of aortic root replacement in adolescent patients with aortic root aneurysm by analyzing the perioperative and follow-up conditions of surgical treatment for adolescent aortic root aneurysm.Methods:The clinical data of patients aged ≤18 years who were admitted to the Beijing Anzhen Hospital from November 2012 to February 2025, diagnosed with aortic root aneurysm by ultrasound or aortic computed tomography angiography (CTA) and requiring surgical intervention, were collected retrospectively. They were divided into the valve-sparing aortic root replacement group (David operation group) and the aortic root replacement group (Bentall operation group) according to the surgical method. The perioperative results and long-term follow-up results of the two groups were analyzed. Kaplan-Meier survival curves were drawn to compare the reoperation intervention rate between the two groups.Results:A total of 25 patients were included in this study, including 17 in the Bentall group and 8 in the David group. There were no statistically significant differences in gender, age, blood routine, liver and kidney function, coagulation function, and electrolyte internal environment between the two groups (all P>0.05). There were no statistically significant differences in operation time and intensive care unit stay between the two groups (all P>0.05). Compared with the Bentall operation group, the intraoperative blood loss in the David operation group was more ( P<0.05). During the follow-up, no reoperation occurred in the Bentall operation group, while 3 patients in the David operation group had long-term re-intervention. The long-term reoperation intervention rate in the David operation group was higher than that in the Bentall group ( P=0.042), but there was no statistically significant difference in the aortic valve-related surgical intervention rate between the two groups ( P=0.15). Conclusions:For adolescent patients with aortic root aneurysm, although David operation may face long-term reoperation intervention, this intervention may not be due to the difference in surgical methods. Both Bentall operation and David operation are safe and reliable, with good perioperative results and stable medium and long-term prognosis.