Andrological diseases have become an important public health problem threatening men's health worldwide， which significantly affects the quality of life of patients and brings a heavy disease burden. Western medicine often faces the dilemma of obvious side effects and limited efficacy. Traditional Chinese medicine has unique advantages in the prevention and treatment of andrological diseases and has accumulated rich clinical experience. Epimedii Folium， as a traditional Chinese medicine for strengthening kidney and Yang， exerts a key therapeutic effect on andrology diseases through multi-component synergy， multi-target regulation， and multi-pathway intervention. Recent studies have found that the main active components of Epimedii Folium， such as icariin， icariside， and icaritin， are the key material basis for the treatment of andrological diseases. The active components of Epimedii Folium can play a role in common andrological diseases such as erectile dysfunction， male infertility， and prostate cancer by regulating the activity of the nitric oxide/cyclic guanosine monophosphate （NO/cGMP） pathway， participating in oxidative stress response， regulating the secretion of hypothalamic-pituitary-gonadal axis hormones， improving spermatogenic dysfunction， and inhibiting the proliferation of cancer cells. However， the systematic action network and molecular mechanisms of the active components of Epimedii Folium have not been fully elucidated， thereby limiting its potential for clinical translation and application. In the future， it is necessary to combine cutting-edge technologies such as metabolomics， single-cell sequencing， and targeted nanoscale drug delivery systems， strengthening the research on the compatibility rules of active components and organ-specific delivery， providing a scientific basis for the development of innovative andrology traditional Chinese medicine formulas with international competitiveness， and promoting the innovation and breakthrough of andrology disease treatment modes.

ObjectiveTo investigate the mechanism by which Haizao Yuhu Tang regulates the nuclear receptor subfamily 4 group A member 1 （NR4A1）signaling pathway to modulate CD8-positive T lymphocyte （CD8⁺T） cell exhaustion-mediated immune escape in transgenic mice with papillary thyroid carcinoma （PTC）. MethodsSixty C57BL/6J mice carrying the conditional BRAF^V600E point mutation were randomly assigned to five groups （n=12）： Model， low-dose （7.28 g·kg^-1·d^-1） Haizao Yuhu Tang， medium-dose （14.56 g·kg^-1·d^-1） Haizao Yuhu Tang， high-dose （29.12 g·kg^-1·d^-1） Haizao Yuhu Tang， and vemurafenib （PLX4032， 0.02 g·kg^-1·d^-1）. In addition， 12 BRAF^V600E-negative mice were selected as the control group. All the groups received continuous intervention for 8 weeks. After treatment， the thyroid tumor weight and volume of mice in each group were measured. Hematoxylin and eosin （HE） staining was performed to observe the morphological characteristics of thyroid tumors. Enzyme-linked immunosorbent assay （ELISA） was adopted to quantify the serum levels of interferon-γ （IFN-γ）， interleukin-2 （IL-2）， tumor necrosis factor-α （TNF-α）， C-X-C motif chemokine ligand 9 （CXCL9）， and C-X-C motif chemokine ligand 10 （CXCL10）. Flow cytometry was employed to determine the proportion of cytotoxic CD8⁺T cells in the tumor tissue. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of molecules related to the NR4A1 signaling pathway. ResultsCompared with the control group， the model group showed significantly increased thyroid tumor volume and weight （P<0.01）. Compared with the model group， the low-dose， medium-dose， and high-dose Haizao Yuhu Tang groups and the vemurafenib group exhibited varying degrees of reduction in thyroid tumor volume and weight （P<0.05， P<0.01）， with the medium-dose Haizao Yuhu Tang group and the vemurafenib group showing the most pronounced therapeutic effects （P<0.01）. Compared with the model group， the low-dose， medium-dose， and high-dose Haizao Yuhu Tang groups and the vemurafenib group showed increased serum levels of IFN-γ， IL-2， TNF-α， CXCL9， and CXCL10， decreased mRNA and protein levels of NR4A1， Programmed cell death-1 （PD-1）， and Programmed cell death-ligand 1 （PD-L1）， and enhanced cytotoxic activity of CD8⁺T cells （P<0.05， P<0.01） Among these groups， the medium-dose Haizao Yuhu Tang group exhibited the optimal therapeutic effects. In addition， compared with that in the model group， T-cell factor-1 （TCF-1） expression was increased in the low-dose， medium-dose， and high-dose Haizao Yuhu Tang groups （P<0.01）， whereas no significant change in TCF-1 expression was observed in the vemurafenib group. ConclusionHaizao Yuhu Tang may restore the cytotoxic function of CD8⁺T cells by inhibiting the NR4A1 signaling pathway， thereby suppressing immune evasion in PTC and delaying PTC growth.

OBJECTIVE: To assess the osteogenesis height in maxillary sinus segment one year after zygomatic implantation by imaging methods, and evaluate the influence of patient factors, maxillary sinus anatomical factors and surgical factors on postoperative osteogenesis height. METHODS: This study is a retrospective study, including patients who underwent zygomatic implantation and whose zygomatic implants passed through the maxillary sinus at the Department of Implantology, Peking University School and Hospital of Stomatology from July 2017 to January 2022. Preoperative and postoperative cone beam CT (CBCT)was taken to measure and calculate the average osteogenesis height (AOH) in maxillary sinus segment of the zygomatic implants, then the residual bone height, the width and morphology of the maxillary sinus floor in the buccal and palatal directions were measured. Besides, the integrity of Schneiderian membrane during implant surgery, and the general information of the patients and zygomatic implants were recorded. By comparing anatomical situations and surgical characteristics, the differences of AOH under different conditions were analyzed. Then AOH was divided into two groups (obvious osteogenesis group and non-obvious osteogenesis group) using the median as the threshold, and the influencing factors of osteogenesis were evaluated using mixed effect generalized linear model univariable and multivariable analysis. RESULTS: A total of 47 zygomatic implants were implanted in 24 patients. During the average follow-up period of 12.1 months, there was no implant failure, and the implant survival rate was 100%. Postoperative CBCT showed that 43 zygomatic implants had osteogenic images in the maxillary sinus segment, most of which originated from the floor of the maxillary sinus, and the median AOH was 3.1 mm [interquartile range (IQR): 4.0 mm]. In terms of maxillary sinus width, there were 31 cases (66.0%) of wide type and 16 cases (34.0%) of narrow type. In the aspect of buccal and palatal morphology, 17 cases were taper (36.2%), 20 cases were round (42.6%), and 10 cases were flat (21.3%). The median of residual bone height was 2.8 mm (IQR: 2.2 mm) before operation. Univa-riate analysis of mixed effect generalized linear model showed that postoperative obvious osteogenic rate was related to the residual bone height (OR=2.09, P=0.006). Multivariate analysis showed that the resi-dual bone height (OR=2.55, P=0.022) and the shape of a taper maxillary sinus (OR=11.44, P=0.040) had a significant impact on the postoperative obvious osteogenic rate. CONCLUSION The maxillary sinus floor showed osteogenic images 1 year after the zygomatic implantation surgery. Larger residual bone height and the shape of a taper maxillary sinus may be favorable factors for osteogenesis.
Humans ; Maxillary Sinus/surgery* ; Cone-Beam Computed Tomography ; Retrospective Studies ; Zygoma/diagnostic imaging* ; Male ; Female ; Osteogenesis/physiology* ; Middle Aged ; Adult ; Dental Implants ; Aged ; Dental Implantation, Endosseous/methods*

Objective:To investigate the characteristics of visual and auditory sustained attention and sex differences in pupils of different grades.Method:Totally 231 students from grades 1 to 6 participated in this stud-y.The development and sex differences of sustained attention were measured by average reaction times,coefficients of variation for reaction times,omission error rates and commission error rates in visual and auditory two-choice re-action time(CRT)tasks.Result:The students in grade 5 had significantly slower visual average reaction times and coefficients of variation for reaction times(P＜0.001 or P＜0.05)than those in grade 3.The students in grade 5 had significantly lower auditory average reaction times,coefficients of variation for reaction times,omission error rates and commission error rates(P＜0.001 or P＜0.01)than those in grade 1.There was no significant sex differ-ences in visual or auditory average reaction times,coefficients of variation for reaction times or omission error rates(Ps＞0.05).Conclusion:There would be age differences in characteristics of both visual and auditory sustained at-tention in pupils,and may be no sex difference in visual or auditory sustained attention.

Objective:To explore the relationship between suicide attempts,school bullying,and psychological resilience in children and adolescents with major depressive disorder(MDD)and school bullying and psychological resilience.Methods:A total of 784 patients with MDD aged 10 to 18 years were included.The Chinese version of the Olweus Bullying Victimization Questionnaire,Adolescent Psychological Resilience Scale,and a suicide attempt assessment were utilized to evaluate school bullying,psychological resilience,and suicide attempt.Stepwise logistic regression was applied to identify the associated factors of suicide attempts.Results:The occurrence of suicide at-tempts in children and adolescents with MDD was positively associated with physical bullying(OR=1.85,95％CI:1.14-3.02)and indirect bullying(OR=1.48,95％CI:1.06-2.04),and negatively associated with higher levels of goal focus(OR=0.62,95％CI:0.45-0.85)and positive cognition(OR=0.62,95％CI:0.45-0.85)at higher levels.Conclusion:Bullying significantly increases the risk of suicide attempts in children and adolescents with MDD,while higher psychological resilience could mitigate this risk.

Objective:To investigate the characteristics of visual and auditory sustained attention and sex differences in pupils of different grades.Method:Totally 231 students from grades 1 to 6 participated in this stud-y.The development and sex differences of sustained attention were measured by average reaction times,coefficients of variation for reaction times,omission error rates and commission error rates in visual and auditory two-choice re-action time(CRT)tasks.Result:The students in grade 5 had significantly slower visual average reaction times and coefficients of variation for reaction times(P＜0.001 or P＜0.05)than those in grade 3.The students in grade 5 had significantly lower auditory average reaction times,coefficients of variation for reaction times,omission error rates and commission error rates(P＜0.001 or P＜0.01)than those in grade 1.There was no significant sex differ-ences in visual or auditory average reaction times,coefficients of variation for reaction times or omission error rates(Ps＞0.05).Conclusion:There would be age differences in characteristics of both visual and auditory sustained at-tention in pupils,and may be no sex difference in visual or auditory sustained attention.

Objective:To explore the relationship between suicide attempts,school bullying,and psychological resilience in children and adolescents with major depressive disorder(MDD)and school bullying and psychological resilience.Methods:A total of 784 patients with MDD aged 10 to 18 years were included.The Chinese version of the Olweus Bullying Victimization Questionnaire,Adolescent Psychological Resilience Scale,and a suicide attempt assessment were utilized to evaluate school bullying,psychological resilience,and suicide attempt.Stepwise logistic regression was applied to identify the associated factors of suicide attempts.Results:The occurrence of suicide at-tempts in children and adolescents with MDD was positively associated with physical bullying(OR=1.85,95％CI:1.14-3.02)and indirect bullying(OR=1.48,95％CI:1.06-2.04),and negatively associated with higher levels of goal focus(OR=0.62,95％CI:0.45-0.85)and positive cognition(OR=0.62,95％CI:0.45-0.85)at higher levels.Conclusion:Bullying significantly increases the risk of suicide attempts in children and adolescents with MDD,while higher psychological resilience could mitigate this risk.

Objective To investigate the mechanism of inhibitory effect of mollugin on hepatocellular carcinoma based on the ferroptosis pathway.Methods HepG2 cells were cultured in vitro and divided into control group,mollugin low-(10 μmol/L),medium-(20 μmol/L),and high-dosage(40 μmol/L)groups based on the inhibitory concentration of 50%.The cell viability was detected by CCK-8 method,cytotoxicity was detected by LDH kit,and the ability of cell colony formation was observed by clone formation assay,the contents of GSH,MDA,ROS,SOD,superoxide,lipid peroxide and MMP were detected,the protein expression of ferroptosis suppressor protein 1(FSP1),GTP cyclohydrolase 1(GCH1),dihydroorotate dehydrogenase(DHODH)and glutathione peroxidase 4(GPX4)were detected by Western blot,the mRNA expression of FSP1,DHODH,GCH1 and GPX4 were detected using RT-qPCR.The effect of mollugin on cell viability and GSH,MDA contents of hepatocellular carcinoma cells were observed under overexpression and silencing of GPX4 by mollugin.Results The medium-and high-dose of mollugin could reduce the number of clone formation in HepG2 cells,decrease the GSH content and SOD activity of cells,increase the content of MDA,superoxide,lipid peroxides and ROS,and decreased MMP(P<0.001).The intervention of mollugin had no significant effect on the expressions of FSP1,GCH1,DHODH protein and mRNA in HepG2 cells,but could decrease the expression of GPX4 protein and mRNA(P<0.001).Overexpression and silencing experiments confirmed that GPX4 was the core target for the regulation of ferroptosis by mollugin.Conclusion Mollugin mainly exerts its anti-liver cancer effect by regulating GPX4 mediated ferroptosis.

Objective·To investigate the effects of sennoside A(SA)on the formation of atherosclerotic plaque and the expression of 5-hydroxytryptamine(5-HT)and its receptor in mice with diabetes mellitus type 2(T2DM).Methods·Twelve mice with knocked-out apolipoprotein E gene were randomly divided into two groups,namely the model group and the model+SA group,with six mice in each group.Six C57BL/6J mice with the same genetic background were used as the control group.The control group was fed with normal diet,and the model group and the model+SA group were given intraperitoneal injection of streptozotocin(30 mg/kg)daily on the basis of high-fat diet to establish a model of T2DM.The model+SA group was given SA daily by gavage for 8 weeks,and the control group and the model group were given equal volume of distillation-distillation H2O by gavage.The body weight,fasting blood glucose(FBG)and 2-h postprandial blood glucose of mice were compared before and after modeling and treatment.The area of aortic plaque was observed by oil red O staining and hematoxylin-eosin(H-E)staining,and the level of 5-HT in serum and thoracic aorta was measured by ELISA kit.Western blotting was used to detect the expression of 5-hydroxytryptamine receptor 2B(HTR2B)and serotonin transporter(SERT)in thoracic aorta of mice.Results·Compared with the control group,the body weight,FBG and 2-h postprandial blood glucose in the model group increased,and glucose metabolism was disordered.The expression of HTR2B and SERT protein in thoracic aorta increased,while the concentration of 5-HT in thoracic aorta decreased.The serum 5-HT concentration increased(all P<0.05).After treatment with SA,compared with the model group,the body weight of the model+SA group decreased,and FBG and 2-h postprandial blood glucose were significantly improved.The area of aortic plaque and the expression of HTR2B and SERT protein in thoracic aorta significantly decreased,while the concentration of 5-HT increased.The serum 5-HT concentration decreased(all P<0.05).Conclusion·SA can reduce atherosclerotic plaque area in T2DM mice,which may be related to lowering blood glucose and inhibiting the expression of 5-HT and its receptor.

Objective To evaluate the role of microglia in paraventricular nucleus (PVN) in sus-ceptibility to depression in rats with chronic visceral pain. Methods Ninety-six pathogen-free healthy male Sprague-Dawley rats, aged 8 days, were divided into 6 groups (n= 16 each) using a random number table: sham operation group (S group), chronic visceral pain group (CHVP group), sham operation plus colorectal distension group (S+C group), chronic visceral pain plus colorectal distension group (CHVP+C group), chronic visceral pain plus phosphate buffer solution plus colorectal distension group (CHVP+P+C group) and chronic visceral pain plus minocycline plus colorectal distension group (CHVP+M+C group). Colorectal distension was not performed in S group. In CHVP group, chronic visceral pain was induced by performing colorectal distension twice daily on postnatal days 8, 10, and 12. Phosphate buffer solution 0. 5μl was injected into PVN by stereotaxic method at 8th week after birth in CHVP+P+C group, and 2％ mi-nocycline 0. 5 μl was injected into PVN at 8th week after birth in CHVP+M+C group. Eight rats in each group were selected 2 h later for measurement of visceral pain threshold. In S+C, CHVP+C, CHVP+P+C and CHVP+M+C groups, colorectal distension was performed for 2 times, open field test and sucrose preference test were then performed, the rats were sacrificed and PVN was removed for determination of micro-glial activation by immunofluorescence. Results The pain threshold was significantly decreased in CHVP, CHVP+C, CHVP+P+C and CHVP+M+C groups as compared with S and S+C groups (P<0. 05). The pain threshold was significantly increased in CHVP+M+C group when compared with CHVP +P +C group (P<0. 05). Compared with S, CHVP and S+C groups, the total locomotor distance, the number of rea-ring and sucrose consumption were significantly reduced, and the proportion of activated microglia in PVN was increased in CHVP+C, CHVP+P+C and CHVP+M+C groups (P<0. 05). Compared with CHVP+P+C group, the total locomotor distance, the number of rearing and sucrose consumption were significantly in-creased, and the proportion of activated microglia in PVN was decreased in CHVP+M+C group (P<0. 05). Conclusion Microglia in PVN is involved in regulation of susceptibility to depression in rats with chronic visceral pain.