Objective To investigate the effects and possible mechanisms of the growth differentia-tion factor 15(GDF-15)/glial-derived neurotrophic factor receptor alpha-like(GFRAL)pathway on the progression of atherosclerosis in ApoE-/-mice.Methods Eight 8-week-old male ApoE-/-mice were randomly divided into control group and rGDF-15 group.The mice in the control group received an injection of phosphate-buffered saline via tail vein once a week after 4 weeks of high-fat diet feeding,and those in the rGDF-15 group received an injection of recombinant GDF-15(0.05 mg/kg)via tail vein once a week after 4 weeks of high-fat diet feeding.The mice were fed with high-fat diet for another 8 weeks,the body weight was monitored during this period.After 12 weeks'feeding,the mice were euthanized.Another 4 normal mice(at the same age,20 weeks old)were subjected and served as normal control group.The levels of fasting blood glucose,blood lip-ids,cortisol,and aldosterone were compared among the three groups.Oil red O staining was used to evaluate plaque size in the aorta,and immunohistochemistry was employed to assess the expression of GDF-15 and GFRAL in the brain tissue.Results The serum level of GDF-15 was higher in the rGDF-15 group than in the control group(52.59±2.90 ng/ml vs 20.09±1.27 ng/ml,P＜0.01).The weight of mice was significantly lower in the rGDF-15 group than the con-trol group during Week 11(28.60±0.22 g vs 29.47±0.25 g,P＜0.01)and 12(28.98±0.22 g vs 30.35±0.13 g,P＜0.01).The rGDF-15 group had a statistically lower level of triglycerides(0.22±0.02 mmol/L vs 0.38±0.09 mmol/L,P＜0.05),lighter plaque burden[(22.22±2.58)％vs(31.61±3.51)％,P＜0.01],and enhanced expression levels of GDF-15 and GFRAL in the brain tissue(0.088±0.007 vs 0.030±0.006,0.031±0.003 vs 0.010±0.001,P＜0.01).The levels of cor-tisol and aldosterone in the control group and rGDF-15 group were significantly higher than those in the normal group(P＜0.01).The aldosterone level in the rGDF-15 group was significantly re-duced compared to the control group(22.013.67 mg/ml vs 87.29±8.63 mg/ml,P＜0.01).Conclusion GDF-15 may regulate body weight and triglyceride and aldosterone levels through GFRAL,and then affect the progression of atherosclerosis.

Objective:To investigate the clinical effect of extraperitoneal robot-assisted laparoscopic modified Y-V plasty(LMYVP)in the treatment of refractory bladder neck contracture(BNC).Methods:We retrospectively analyzed the clinical data on 10 cases of refractory BNC after transurethral resection of the prostate between September 2020 and January 2023,all with a history of recurrent urethral dilatation and at least two failures in transurethral surgical treatment of scarring.After definite diagnosis and re-moval of some of the scar tissues to flatten the elevated bladder neck under the cystoscope,we performed robot-assisted LMYVP using the da Vinci Si robotic system and a four-port extraperitoneal approach.The surgical procedure involved an inverted T-shaped incision in the bladder neck and urethral stricture ring,an inverted V-shaped excision of the scar area at the 3-9 o'clock position on the ventral side of the prostatic urethra,continuous full-layer suturing of the bladder neck and inverted V-shaped urethra with 3-0 barbed thread,and indwelling of an F20 silicone catheter for 2 weeks.At 3 months after surgery,we performed cystoscopic examination,measured the maximum urinary flow rate(Qmax),and obtained the IPSS and quality of life(QOL)scores of the patients.Results:Operations were successfully completed in all the cases.At 3 months after surgery,the patients showed significantly increased Qmax([3.65±1.27]vs[20.3±1.77]ml/s,P＜0.05),IPSS(5.9±2.02 vs 30±1.15,P＜0.05)and QOL score(1.3±0.95 vs 5.2±0.79,P＜0.05)compared with the baseline.Cystoscopy revealed a wide and flat bladder neck with good survival and hemody-namics of the bladder flap.All the patients met the criteria for clinical cure at a median follow-up of 13.2 months.Conclusion:Extraper-itoneal robot-assisted LMYVP provides a new strategy for urinary tract reconstruction in the management of refractory BNC,with the ad-vantages of minimal invasiveness,high efficiency and high success rate.

Objective To compare and analyze the differences between customized models and commercial universal models in the segmentation of organs-at-risk in cervical cancer,and to investigate the feasibility of customized models.Methods A retrospective analysis was conducted on 270 cervical cancer patients.Senior clinicians manually delineated organs-at-risk,including the bladder,rectum,small intestine,pelvic bone marrow,femoral heads,and kidneys.The cases were randomly selected to develop customized models,with 202 cases allocated to the training set,38 cases to the test set,and 30 cases to the validation set.The universal and customized models were used for segmentation on the test set,and the automatic segmentation results obtained by the two models were compared with manual segmentation results to assess the performance of the customized model.Results Both customized model and universal model had comparable DSC values to manual segmentation,demonstrating satisfactory delineation outcomes(DSC values ranging from 0.7 to 0.9).However,in terms of deviation of centroid and 95％Hausdorff distance,the customized model surpassed the universal model.Conclusion Compared with the universal model,the customized model offers superior accuracy in delineating the structures of organs-at-risk in cervical cancer.As the customized model is optimized based on specific datasets,it provides precise support for clinical decision-making and holds promising applications in the treatment of cervical cancer.

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

AIM: To investigate the apoptosis and molecular mechanism of human hepatocellular carcinoma HepG2 cells induced by ginsenoside Rh4.METHODS: Human hepatocellular carcinoma HepG2 cells were treated with ginsenoside Rh4 at doses of 10, 20 and 40 μmol/L, and the inhibitory effect of ginsenoside Rh4 on HepG2 cell viability was measured by MTT assay.The apoptotic rate of HepG2 cells was analyzed by flow cytometry.The morphological changes of the HepG2 cells were observed by Hoechst 33258 and TUNEL staining.The expression of apoptosis-related proteins Bax, Bcl-2, caspase-3 and caspase-9 was determined by Western blot.RESULTS: Ginsenoside Rh4 promoted apoptosis of HepG2 cells in a dose-dependent manner.TUNEL and Hoechst 33258 staining showed that the cells appeared obvious shrinking, swelling and rupture after treated with ginsenoside Rh4 for 24 h.The results of Western blot showed that with the increasing concentrations of ginsenoside Rh4, the expression of pro-apoptotic proteins Bax, cleaved caspase-3 and caspase-9 increased, while anti-apoptotic protein Bcl-2 decreased gradually.CONCLUSION: Ginsenoside Rh4 induces apoptosis of human hepatocellular carcinoma HepG2 cells, and the main mechanism may be related to down-regulation of Bcl-2 and up-regulation of Bax, cleaved caspase-3, and caspase-9.

Objective To discuss the clinical application of percutaneous transhepatic removal of gall-stone technique in treating common bile duct (CBD) stones.Methods Between January 2013 and January 2015,a total of 25 patients with CBD stones underwent lithotomy procedure via percutaneous transhepatic route.First,under ultrasound or fluoroscopy guidance percutaneous transhepatic cholangiography (PTC) was performed with subsequent placement of an 8 F rsheath;then,a balloon of 8-12 mm diameter was employed to dilate the papilla;mechanical lithotripsy was adopted when the stone size exceeded 12 mm;finally,through guide-wire exchange technique the stone-retrieval balloon was used to push the stones into the intestinal tract through the sphincter of duodenal papilla.Results The reasons to receive percutaneous transhepatic removal of gall-stone technique in the 25 patients included previous gastrointestinal surgery (n=18),endoscopic treatment failure (n=3),unwilling to receive endoscopic treatment (n=3),and other reasons (n=1).Successful removal of stones was accomplished in all 25 patients.After the treatment,complications occurred in 3 patients (12％),including fever (n=2) and liver abscess formation (n=1).The patients were followed up for 0.5-3 years;two patients died of tumor recurrence and metastasis,and one patient developed recurrence of common bile duct stones.No reflux cholangitis occurred.Conclusion For the treatment of CBD stones,percutaneous transhepatic removal of gall-stone technique carries higher technical success rate with lower incidence of complications,therefore,this technique can be used for the patients who are not suitable for endoscopic treatment or in whom endoscopic treatment failed.

OBJECTIVETo evaluate the high-resolution and color Doppler ultrasonographic (US) characteristics of cervical lymphadenopathy in patients with infectious mononucleosis.

METHODSHigh-resolution and color Doppler US were performed in 30 patients aged 2 to 30 years with a total of 59 palpable enlarged cervical lymph nodes due to infectious mononucleosis. The US characteristics of the nodes including shape,echotexture,hilum,border,matting,cystic necrosis,calcification and vascular pattern were assessed. Three patients received cervical lymph nodes biopsies.

RESULTSThe common US findings of cervical lymphadenopathy due to infectious mononucleosis were round shape (69.5%),bilateral distribution (96.7%),matting (83.3%) [even bilateral matting (66.6%)],indistinct margin (79.7%),absence of hilum (66.1%),heterogeneous echotecture (61.0%),and central hilar vascular pattern(89.8%). In 2 patients with absence of the echoic hilum,lymph nodes biopsies showed histological features including marked effacement of the normal architecture in the medullary region accompanied by a mixed proliferation of lymphocytes and histiocytes. In all infectious mononucleosis nodes with a hilum,85.0% had heterogeneously hypo/iso-echoic hila and indistinct demarcation to the cortex. One of them underwent lymph node biopsy and histological findings showed obvious dilation of the sinus oidal lumen and proliferation of histiocytes.

CONCLUSIONAlthough several ultrasonographic characteristics frequently present in the nodes of infectious mononucleosis are not specific,the combination of ultrasound findings may be valuable in differential diagnosis.

Adolescent ; Adult ; Calcinosis ; Child ; Child, Preschool ; Diagnosis, Differential ; Humans ; Infectious Mononucleosis ; Lymphatic Diseases ; diagnostic imaging ; Neck ; Ultrasonography ; Young Adult

Abstract?AlM: To observe the anterior chamber angle shape of patients with diabetic retinopathy ( DR) at different stages using OCT, and to explore a more sensitive and accurate glaucoma preventing measure.?METHODS: A total of 613 cases of DR patients were divided into proliferation phase group ( 353 cases ) and background phase group ( 260 cases ) , another 100 cases of patients with only diabetes were selected as control group. OCT was used to detect the anterior chamber angle related parameters, including angle opening distance ( AOD) , trabecular-iris space area ( TlSA) , angle recess area ( ARA ) , anterior chamber depth ( ACD ) and anterior chamber angle ( ACA) .?RESULTS: There were significant difference among AOD500, AOD750, TlSA500, TlSA750, ARA500 and ARA750 of control group, proliferation phase group and background phase group ( P< 0. 01 ). The proliferation phase group was the lowest, AOD500, AOD750, TlSA500, TlSA750, ARA500 and ARA750 were 0. 60 ± 0. 22mm, 0. 78 ± 0. 39mm, 0. 22 ± 0. 12mm2 , 0. 45 ± 0. 19mm2 , 0. 29 ± 0. 18mm and 0. 46 ± 0. 15mm, respectively. There were significant difference among ACA500, ACA750, ACD500 and ACD750 of control group, proliferation phase group and background phase group ( P< 0. 01 ). The proliferation phase group was the lowest, ACA500, ACA750, ACD500 and ACD750 were 30. 29o ± 8. 19o, 21. 20o ± 7. 40o, 2. 32 ± 0. 23μm and 2. 52±0. 16μm, respectively. ln addition, ROC results indicated that all these indices exert significant difference on evaluating the stage of DR. ?CONCLUSlON: Anterior chamber angle shape detected using OCT can reflect the change of retinopathy. OCT is an accurate and simple technique for detecting DR staging.

OBJECTIVETo observe the clinical effects of the no-flip procedure with the Chinese Shang Ring when circumcising adult males with redundant prepuce or phimosis, and to discuss its advantages and disadvantages.

METHODSUsing the no-flip Shang Ring technique, we performed circumcision for 167 adult males aged 18 -72 (mean 27.8) years with redundant prepuce or phimosis, and analyzed the clinical data, including the operation time, postoperative complications, ring-removal time, and postoperative appearance of the penis.

RESULTSComplete follow-up data of 94 cases (56.29%) were obtained. The mean operation time was (5.03 +/- 0.71) minutes and the average ring-removal time was (18.83 +/- 6.70) days. The primary postoperative complications were edema (35 cases [37.23%] at 2 weeks and 9 cases [9.57%] at 4 weeks), including 2 severe cases (2.13%), and infection (3 cases [3.19%]). The pain scores were 2.01 +/- 2.46 during the procedure and 4.52 +/- 2.53 at 24 hours postoperatively. Slipping of the outer ring occurred in 1 case, and delayed removal of the ring in 30 cases (31.91%).

CONCLUSIONAdult male circumcision with the no-flip Shang Ring technique is recommended for its short operation time, simple procedure, fewer postoperative complications, less pain, and better incision appearance.

Adult ; Aged ; Circumcision, Male ; adverse effects ; instrumentation ; methods ; Edema ; etiology ; Humans ; Male ; Middle Aged ; Operative Time ; Pain, Postoperative ; etiology ; Penile Diseases ; etiology ; Penis ; abnormalities ; surgery ; Phimosis ; surgery ; Postoperative Complications ; Postoperative Period ; Prostheses and Implants ; Young Adult