Objective:To study the outcomes of the modified Devine + Shiraki surgical approach in the treatment of severe concealed penis.Methods:A retrospective analysis was conducted on the clinical data of initially treated patients with severe concealed penis admitted to the Department of Urology, Henan Provincial People’s Hospital from March 2020 to September 2022. The therapeutic effects of three surgical approaches (Devine, Shiraki, and modified Devine + Shiraki) were analyzed and compared. The Devine approach mainly focuses on eliminating the pathological morphology of the concealed penis, thoroughly releasing the penile shaft, and correcting the concealed state; the Shiraki approach emphasizes the rational distribution of skin flaps; the key of the modified Devine + Shiraki approach lies in combining the advantages of the two approaches, achieving both complete correction of the concealed state and rational distribution of skin flaps. Improvements were made to the conventional surgical sequence: skin flap distribution was pre-designed before correcting the concealed penis to avoid difficulties in skin flap arrangement caused by degloving, thereby preventing postoperative complications such as stricture rings, lymphedema, or erectile pain. Three months after the operation, follow-up was performed to assess incision healing, presence of lymphedema or stricture rings, satisfaction with penile exposure, recurrence of the concealed state, urination patency, presence of urethral injury, and normal erectile function. A patient satisfaction survey was conducted 6 months after the operation. Measurement data with normal distribution were expressed as Mean± SD, and one-way analysis of variance was used for comparison among the three groups; categorical variables were expressed as case numbers and percentages, and chi-square test was used for comparison among the three groups. Results:Eighty, fifty, and forty-five male children were enrolled in the Devine + Shiraki group, Devine group, and Shiraki group, respectively. There were no statistically significant differences in age and body mass index (BMI) among the three groups [age: (7.6±4.5) years vs. (7.2±4.4) years vs. (6.7±4.2) years, F=0.61, P=0.546; BMI: (17.4±3.1) kg/m 2 vs. (17.7±3.2) kg/m 2 vs. (18.0±3.3) kg/m 2,F=0.57, P=0.565]. During surgery, all concealed penile shafts were completely released, and the penile skin was rationally distributed. The postoperative follow-up period ranged from 3 months to 18 months, with an average follow-up time of 13.6 months. At the 3-month postoperative follow-up, all three groups showed satisfactory wound healing with no signs of infection or skin flap necrosis; penile skin coverage was adequate, and all children demonstrated unobstructed urination without evidence of urethral injury; normal erectile function was preserved in all cases, with no reports of erectile dysfunction or pain. The recurrence rate of the concealed penis in the Devine + Shiraki group was significantly lower than that in the Devine group and Shiraki group, with a statistically significant difference [0 (0/80) vs. 6.0% (3/50) vs. 31.1% (14/45), χ2=32.88, P<0.001]; the proportion of patients without postoperative lymphedema and stricture rings in the Devine + Shiraki group was higher than that in the Devine group and Shiraki group, with a statistically significant difference [97.5% (78/80) vs. 70.0% (35/50) vs. 86.7% (39/45), χ2=20.39, P<0.001]. The Devine+ Shiraki, Devine, and Shiraki groups reported postoperative satisfaction in 76 (95.0%), 35 (70.0%), and 31 (68.9%) cases, respectively. Conclusion:The modified Devine + Shiraki surgical approach has definite efficacy, good safety, and a low incidence of complications, and can be used as an option for the treatment of severe concealed penis.

Objective To observe the value of T1 mapping combining diffusion weighted imaging(DWI)for noninvasive preoperative predicting tumor-infiltrating lymphocyte(TIL)level in invasive breast cancer.Methods Totally 143 patients with invasive breast cancer were retrospectively collected and divided into high group(TIL≥10％,n=73)and low group(TIL＜10％,n=70)according to TIL level by postoperation pathology.Clinicopathological information were collected,MRI features of breast cancer lesions were documented,mean T1 values(T1mean)and mean ADC values(ADCmean)were measured,and then were compared between groups.Multivariate logistic regression analysis was used to identify independent predictive factors of TIL levels,and a nomogram was constructed based on regression model.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to evaluate the predictive value for TIL levels.Results Compared with low group,high group had higher proportion of human epidermal growth factor receptor 2(HER2)positivity(P＜0.05),and showed more circular/oval shapes and more smooth margins but less peritumoral edema(all P＜0.05).Significant differences of lesions enhancement pattern was found between groups(P＜0.05).T1mean and ADCmean were both higher in high group than those in low group(both P＜0.05).Lesions enhancement pattern,T1mean and ADCmean were all independent predictors of TIL levels in breast cancer.The AUC of nomogram combining the above 3 factors for predicting TIL level was 0.848,significantly higher than that of lesions enhancement pattern(AUC=0.569,Z=5.384,P＜0.05)and T1mean(AUC=0.662,Z=3.876,P＜0.05),but not statistically different with that of ADCmean(AUC=0.814,Z=1.578,P=0.115).Decision curve analysis showed that this nomogram had good clinical application value.Conclusion Combining T1 mapping and DWI could effectively predict level of TIL level in breast cancer before surgery.

Phosphodiesterase type 5(PDE5)participates in the physiological functions of multiple organs by regulating the nitric oxide(NO)-cyclic guanosine monophosphate(cGMP)pathway.As a long-acting PDE5 inhibitor,tadalafil has been used clinically for over 20 years and is approved for the treatment of male erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia.Furthermore,tadalafil maintains cGMP levels by inhibiting PDE5,thereby activa-ting the downstream NO-cGMP signaling pathway to exert multiple effects,including relaxing smooth muscle,exerting antioxidant actions,regulating apoptosis,and modulating metabolism.Clinical evidence indicates that tadalafil shows promising therapeutic potential in multi-organ system diseases such as pulmonary arterial hypertension,heart failure,type 2 diabetes,cognitive impair-ment,female infertility,and fetal growth restriction.This article systematically reviews the action mechanisms and research pro-gress of tadalafil in treating diseases beyond erectile dysfunction,aiming to summarize its potential for cross-disease system clini-cal applications and provide references for optimizing treatment strategies for patients with chronic diseases.

BACKGROUND:How to effectively promote bone regeneration and bone reconstruction after bone injury has always been a key issue in clinical bone repair research.The use of biological and degradable materials loaded with bioactive factors to treat bone defects has excellent application prospects in bone repair. OBJECTIVE:To investigate the effect of polylactic acid-glycolic acid copolymer(PLGA)composite scaffold modified by lysine-grafted graphene oxide nanoparticles(LGA-g-GO)on osteogenic differentiation and new bone formation. METHODS:PLGA was dissolved in dichloromethane and PLGA scaffold was prepared by solvent evaporation method.PLGA/GO composite scaffolds were prepared by dispersing graphene oxide uniformly in PLGA solution.LGA-g-GO nanoparticles were prepared by chemical grafting method,and the PLGA/LGA-g-GO composite scaffolds were constructed by blending LGA-g-GO nanoparticles at different mass ratios(1%,2%,and 3%)with PLGA.The micromorphology,hydrophilicity,and protein adsorption capacity of scaffolds of five groups were characterized.MC3T3 cells were inoculated on the surface of scaffolds of five groups to detect cell proliferation and osteogenic differentiation. RESULTS AND CONCLUSION:(1)The surface of PLGA scaffolds was smooth and flat under scanning electron microscope,while the surface of the other four scaffolds was rough.The surface roughness of the composite scaffolds increased with the increase of the addition of LGA-g-GO nanoparticles.The water contact angle of PLGA/LGA-g-GO(3%)composite scaffolds was lower than that of the other four groups(P<0.05).The protein adsorption capacity of PLGA/LGA-g-GO(1%,2%,and 3%)composite scaffolds was stronger than PLGA and PLGA/GO scaffolds(P<0.05).(2)CCK-8 assay showed that PLGA/LGA-g-GO(2%,3%)composite scaffold could promote the proliferation of MC3T3 cells.Alkaline phosphatase staining and alizarin red staining showed that the cell alkaline phosphatase activity in PLGA/LGA-g-GO(2%,3%)group was higher than that in the other three groups(P<0.05).The calcium deposition in the PLGA/GO and PLGA/LGA-g-GO(1%,2%,and 3%)groups was higher than that in the PLGA group(P<0.05).(3)In summary,PLGA/LGA-g-GO composite scaffold can promote the proliferation and osteogenic differentiation of osteoblasts,and is conducive to bone regeneration and bone reconstruction after bone injury.

Objective:To explore the effect of ginsenoside Rg1 on spermatogenic dysfunction in mice caused by diabetes and its mechanism of action.Methods:Eighteen male C57BL mice were randomly divided into control group, the model group and the ginsenoside Rg1 group by completely random method, with 6 mice in each group. Type 2 diabetes models were established in the model group and the ginsenoside Rg1 group by a high-fat diet combined with intraperitoneal injection of streptozotocin, while control group was injected with the same amount of normal saline. After successful modeling, control group was given a regular diet for 8 weeks, while the model group and ginsenoside Rg1 group were given a high-fat diet for 8 weeks. The ginsenoside Rg1 group was also treated with ginsenoside Rg1 medication. Reproductive hormone levels were detected by enzyme-linked immunosorbent assay test kits, and Western blotting was used to detect the expressions of apoptosis-related proteins (Bcl2 protein, Caspase-3 protein, Bax protein), autophagy-related proteins (P62, LC3Ⅰ, LC3Ⅱ, Beclin1), β-Catenin protein, mTOR protein, LAMP1 protein and transcription factor EB. The body weight, blood glucose levels, testicular index of mice in each group were compared, as well as the testicular injury status.Results:The body weight [(18.77±1.14) g], testosterone level [(141.07±8.47) ng/L], follicle-stimulating hormone level [(9.19±0.74) U/L], and luteinizing hormone level [(1 497.91±99.57) pg/L] of mice in the model group were significantly lower than those in the control [(31.57±2.35) g, P<0.001; (171.50±11.76) ng/L, P<0.001; (12.46±1.54) U/L, P<0.001; (1 807.29±92.76) pg/L, P<0.001]; fasting blood glucose level [(20.82±1.11) mmol/L], glycosylated hemoglobin (12.67%±1.03%), the testis index (0.65%±0.03%) were significantly higher than those in the control [(6.40±1.34) mmol/L, P<0.001; 5.17%±1.17%, P<0.001; 0.48%±0.04%, P<0.001]. Compared with the model group, the body weight [(22.62±0.92) g, P=0.023], testosterone level [(172.63±9.20) ng/L, P<0.001], follicle-stimulating hormone level [(12.37±1.15) U/L, P<0.001], and luteinizing hormone level [(1 847.80±108.80) pg/L, P<0.001] of mice in the ginsenoside Rg1 group increased significantly, fasting blood glucose level [(18.63±1.14) mmol/L, P=0.017], glycosylated hemoglobin (8.50%±1.05%, P<0.001) and testicular index (0.54%±0.02%, P<0.001) decreased significantly. Compared with the control, the expressions of P62 ( P=0.039), LC3Ⅱ/LC3Ⅰ( P<0.001), Beclin1 ( P=0.002) and mTOR ( P=0.036) in the testicular tissue of mice in the model group all increased, the expression of β-Catenin ( P<0.001), LAMP1 ( P=0.005), transcription factor EB ( P<0.001) all decreased. Compared with the model group, the expressions of autophagy-related proteins P62 ( P=0.048), LC3Ⅱ/LC3Ⅰ( P<0.001) , Beclin1 ( P=0.023) and mTOR ( P=0.005) in the ginsenoside Rg1 group all decreased, while the expression of β-Catenin ( P=0.001), LAMP1 ( P=0.011) and transcription factor EB ( P=0.022) all increased. Transmission electron microscopy detected a decrease in the number of autophagosomes in the testicles of mice in the model group, and it improved after drug intervention. The HE staining showed that the testes of mice in the model group exhibited phenotypes such as the shedding and disorganization of spermatogenic cells, while ginsenoside Rg1 was able to improve these phenotypes. Conclusion:Ginsenoside Rg1 can improve testicular injury caused by diabetes in mice by regulating autophagy.

Objective:To explore the effect of ginsenoside Rg1 on spermatogenic dysfunction in mice caused by diabetes and its mechanism of action.Methods:Eighteen male C57BL mice were randomly divided into control group, the model group and the ginsenoside Rg1 group by completely random method, with 6 mice in each group. Type 2 diabetes models were established in the model group and the ginsenoside Rg1 group by a high-fat diet combined with intraperitoneal injection of streptozotocin, while control group was injected with the same amount of normal saline. After successful modeling, control group was given a regular diet for 8 weeks, while the model group and ginsenoside Rg1 group were given a high-fat diet for 8 weeks. The ginsenoside Rg1 group was also treated with ginsenoside Rg1 medication. Reproductive hormone levels were detected by enzyme-linked immunosorbent assay test kits, and Western blotting was used to detect the expressions of apoptosis-related proteins (Bcl2 protein, Caspase-3 protein, Bax protein), autophagy-related proteins (P62, LC3Ⅰ, LC3Ⅱ, Beclin1), β-Catenin protein, mTOR protein, LAMP1 protein and transcription factor EB. The body weight, blood glucose levels, testicular index of mice in each group were compared, as well as the testicular injury status.Results:The body weight [(18.77±1.14) g], testosterone level [(141.07±8.47) ng/L], follicle-stimulating hormone level [(9.19±0.74) U/L], and luteinizing hormone level [(1 497.91±99.57) pg/L] of mice in the model group were significantly lower than those in the control [(31.57±2.35) g, P<0.001; (171.50±11.76) ng/L, P<0.001; (12.46±1.54) U/L, P<0.001; (1 807.29±92.76) pg/L, P<0.001]; fasting blood glucose level [(20.82±1.11) mmol/L], glycosylated hemoglobin (12.67%±1.03%), the testis index (0.65%±0.03%) were significantly higher than those in the control [(6.40±1.34) mmol/L, P<0.001; 5.17%±1.17%, P<0.001; 0.48%±0.04%, P<0.001]. Compared with the model group, the body weight [(22.62±0.92) g, P=0.023], testosterone level [(172.63±9.20) ng/L, P<0.001], follicle-stimulating hormone level [(12.37±1.15) U/L, P<0.001], and luteinizing hormone level [(1 847.80±108.80) pg/L, P<0.001] of mice in the ginsenoside Rg1 group increased significantly, fasting blood glucose level [(18.63±1.14) mmol/L, P=0.017], glycosylated hemoglobin (8.50%±1.05%, P<0.001) and testicular index (0.54%±0.02%, P<0.001) decreased significantly. Compared with the control, the expressions of P62 ( P=0.039), LC3Ⅱ/LC3Ⅰ( P<0.001), Beclin1 ( P=0.002) and mTOR ( P=0.036) in the testicular tissue of mice in the model group all increased, the expression of β-Catenin ( P<0.001), LAMP1 ( P=0.005), transcription factor EB ( P<0.001) all decreased. Compared with the model group, the expressions of autophagy-related proteins P62 ( P=0.048), LC3Ⅱ/LC3Ⅰ( P<0.001) , Beclin1 ( P=0.023) and mTOR ( P=0.005) in the ginsenoside Rg1 group all decreased, while the expression of β-Catenin ( P=0.001), LAMP1 ( P=0.011) and transcription factor EB ( P=0.022) all increased. Transmission electron microscopy detected a decrease in the number of autophagosomes in the testicles of mice in the model group, and it improved after drug intervention. The HE staining showed that the testes of mice in the model group exhibited phenotypes such as the shedding and disorganization of spermatogenic cells, while ginsenoside Rg1 was able to improve these phenotypes. Conclusion:Ginsenoside Rg1 can improve testicular injury caused by diabetes in mice by regulating autophagy.

Objective:To study the outcomes of the modified Devine + Shiraki surgical approach in the treatment of severe concealed penis.Methods:A retrospective analysis was conducted on the clinical data of initially treated patients with severe concealed penis admitted to the Department of Urology, Henan Provincial People’s Hospital from March 2020 to September 2022. The therapeutic effects of three surgical approaches (Devine, Shiraki, and modified Devine + Shiraki) were analyzed and compared. The Devine approach mainly focuses on eliminating the pathological morphology of the concealed penis, thoroughly releasing the penile shaft, and correcting the concealed state; the Shiraki approach emphasizes the rational distribution of skin flaps; the key of the modified Devine + Shiraki approach lies in combining the advantages of the two approaches, achieving both complete correction of the concealed state and rational distribution of skin flaps. Improvements were made to the conventional surgical sequence: skin flap distribution was pre-designed before correcting the concealed penis to avoid difficulties in skin flap arrangement caused by degloving, thereby preventing postoperative complications such as stricture rings, lymphedema, or erectile pain. Three months after the operation, follow-up was performed to assess incision healing, presence of lymphedema or stricture rings, satisfaction with penile exposure, recurrence of the concealed state, urination patency, presence of urethral injury, and normal erectile function. A patient satisfaction survey was conducted 6 months after the operation. Measurement data with normal distribution were expressed as Mean± SD, and one-way analysis of variance was used for comparison among the three groups; categorical variables were expressed as case numbers and percentages, and chi-square test was used for comparison among the three groups. Results:Eighty, fifty, and forty-five male children were enrolled in the Devine + Shiraki group, Devine group, and Shiraki group, respectively. There were no statistically significant differences in age and body mass index (BMI) among the three groups [age: (7.6±4.5) years vs. (7.2±4.4) years vs. (6.7±4.2) years, F=0.61, P=0.546; BMI: (17.4±3.1) kg/m 2 vs. (17.7±3.2) kg/m 2 vs. (18.0±3.3) kg/m 2,F=0.57, P=0.565]. During surgery, all concealed penile shafts were completely released, and the penile skin was rationally distributed. The postoperative follow-up period ranged from 3 months to 18 months, with an average follow-up time of 13.6 months. At the 3-month postoperative follow-up, all three groups showed satisfactory wound healing with no signs of infection or skin flap necrosis; penile skin coverage was adequate, and all children demonstrated unobstructed urination without evidence of urethral injury; normal erectile function was preserved in all cases, with no reports of erectile dysfunction or pain. The recurrence rate of the concealed penis in the Devine + Shiraki group was significantly lower than that in the Devine group and Shiraki group, with a statistically significant difference [0 (0/80) vs. 6.0% (3/50) vs. 31.1% (14/45), χ2=32.88, P<0.001]; the proportion of patients without postoperative lymphedema and stricture rings in the Devine + Shiraki group was higher than that in the Devine group and Shiraki group, with a statistically significant difference [97.5% (78/80) vs. 70.0% (35/50) vs. 86.7% (39/45), χ2=20.39, P<0.001]. The Devine+ Shiraki, Devine, and Shiraki groups reported postoperative satisfaction in 76 (95.0%), 35 (70.0%), and 31 (68.9%) cases, respectively. Conclusion:The modified Devine + Shiraki surgical approach has definite efficacy, good safety, and a low incidence of complications, and can be used as an option for the treatment of severe concealed penis.

Objective To observe the value of T1 mapping combining diffusion weighted imaging(DWI)for noninvasive preoperative predicting tumor-infiltrating lymphocyte(TIL)level in invasive breast cancer.Methods Totally 143 patients with invasive breast cancer were retrospectively collected and divided into high group(TIL≥10％,n=73)and low group(TIL＜10％,n=70)according to TIL level by postoperation pathology.Clinicopathological information were collected,MRI features of breast cancer lesions were documented,mean T1 values(T1mean)and mean ADC values(ADCmean)were measured,and then were compared between groups.Multivariate logistic regression analysis was used to identify independent predictive factors of TIL levels,and a nomogram was constructed based on regression model.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to evaluate the predictive value for TIL levels.Results Compared with low group,high group had higher proportion of human epidermal growth factor receptor 2(HER2)positivity(P＜0.05),and showed more circular/oval shapes and more smooth margins but less peritumoral edema(all P＜0.05).Significant differences of lesions enhancement pattern was found between groups(P＜0.05).T1mean and ADCmean were both higher in high group than those in low group(both P＜0.05).Lesions enhancement pattern,T1mean and ADCmean were all independent predictors of TIL levels in breast cancer.The AUC of nomogram combining the above 3 factors for predicting TIL level was 0.848,significantly higher than that of lesions enhancement pattern(AUC=0.569,Z=5.384,P＜0.05)and T1mean(AUC=0.662,Z=3.876,P＜0.05),but not statistically different with that of ADCmean(AUC=0.814,Z=1.578,P=0.115).Decision curve analysis showed that this nomogram had good clinical application value.Conclusion Combining T1 mapping and DWI could effectively predict level of TIL level in breast cancer before surgery.

Phosphodiesterase type 5(PDE5)participates in the physiological functions of multiple organs by regulating the nitric oxide(NO)-cyclic guanosine monophosphate(cGMP)pathway.As a long-acting PDE5 inhibitor,tadalafil has been used clinically for over 20 years and is approved for the treatment of male erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia.Furthermore,tadalafil maintains cGMP levels by inhibiting PDE5,thereby activa-ting the downstream NO-cGMP signaling pathway to exert multiple effects,including relaxing smooth muscle,exerting antioxidant actions,regulating apoptosis,and modulating metabolism.Clinical evidence indicates that tadalafil shows promising therapeutic potential in multi-organ system diseases such as pulmonary arterial hypertension,heart failure,type 2 diabetes,cognitive impair-ment,female infertility,and fetal growth restriction.This article systematically reviews the action mechanisms and research pro-gress of tadalafil in treating diseases beyond erectile dysfunction,aiming to summarize its potential for cross-disease system clini-cal applications and provide references for optimizing treatment strategies for patients with chronic diseases.

Objective:To explore the value of contrast enhancement T1 fluid-attenuated inversion recovery sequence (CE-T1FLAIR) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in detecting metastases.Methods:One hundred and seventy-six patients with pathologically diagnosed malignant tumors and brain metastases accepted enhanced 3.0T MRI scan in Department of Medical Imaging, He'nan Provincial Cancer Hospital from October 2023 to February 2024 were enrolled. Lianying's intelligent brain metastasis AI-assisted detection system and sequences of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR were used to detect the brain metastasis lesions, respectively. Length of the lesions was measured according to Lianying's intelligent brain metastasis AI-assisted detection system, and all lesions were divided into 3 categories: <3 mm, 3-10 mm, and >10 mm. Differences in detection rate in brain metastases of different lengths and locations among the 3 sequences were compared.Results:Detection rates of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR, and FSE CE-T1FLAIR in brain metastases were 99.67%, 90.52%, and 71.02%, which were decreased successively, with significant differences ( P<0.05). Detection rates of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR in brain metastases with length<3 mm (99.24%, 79.95% and 46.45%) or length of 3-10 mm (100%, 98.19% and 87.53%) were decreased successively, with significant differences ( P<0.05). Detection rates of MATRIX CE-T1FLAIR (100%, 80.56% and 64.24%), 3D GRE_fsp CE-T1FLAIR (100%, 97.25% and 76.11%), and FSE CE-T1FLAIR (100%, 91.18% and 70.59%) in metastases at the superficial area of the brain convexity, gray-white matter junction area, and cerebellum were decreased successively, with significant differences ( P<0.05). Detection rates of FSE CE-T1FLAIR in brain metastases in the basal ganglia and brainstem (69.33% and 50%) were significantly lower than those of MATRIX CE-T1FLAIR and 3D GRE_fsp CE-T1FLAIR (97.33% and 92.86%; 88% and 78.57%, P<0.05). Conclusion:MATRIX CE-T1FLAIR sequence is better than 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR sequences in detecting brain metastases, especially for metastases with length<10 mm and metastases located at the superficial area of the brain convexity, gray-white matter junction area and cerebellum.