Abstract The incidence of fragility fractures and related mortality caused by male osteoporosis (OP) are both higher than in females. Male bone health was regulated by a sophisticated network involving both androgens and estrogens. Androgens can directly promote bone formation and inhibit bone resorption through androgen receptors on osteoblasts and osteocytes. They can also be converted into estrogens via the action of aromatase and subsequently regulate bone metabolism through estrogen receptors. Declining sex hormone levels, an imbalance in the estrogen-to-androgen ratio, and the resulting disruption in bone metabolic pathways collectively contribute to the development and progression of male OP. Moreover, androgens cannot fully compensate for the bone metabolic imbalance induced by estrogen deficiency. This article reviewed research on the role and mechanism of sex hormones in male OP, as well as studies related to the risks of sex hormone therapy for OP, so as to provide the references for improving control and treatment strategies of male OP.

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

ObjectiveThe mechanisms underlying therapeutic efficacies of Detumescence Analgesic Plaster was analyzed based on "effect-target" associations. MethodBased on CNKI and PubMed databases， the chemical components of Artemisia seed， bastard speedwell， and menthol in Detumescence Analgesic Plaster were collected. The capacity of transdermal absorption was predicted based on the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0）. Golden Triangle of compounds with Accepted used for candidate target prediction based on the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0）according to the similarity of chemical structures. At the same time， the SoFDA data platform was employed to collect the symptoms related to the efficacy of Detumescence Analgesic Plaster and its related genes information. In addition， based on the interaction between the above-mentioned candidate targets and their efficacy-related genes， the "effect-target" interaction network of Detumescence Analgesic Plaster was constructed. The key targets by topological features calculation， and functional mining was carried out to explain the efficacy mechanism of Detumescence Analgesic Plaster. ResultA total of 165 candidate targets were obtained based on ETCM 2.0 and TCMIP v2.0 databases， and symptoms related to the efficacy of clearing heat， detumescence， and relieving pain， as well as 1 744 related genes were collected based on the SoFDA database. Network construction and analysis showed that the core effect targets of Detumescence Analgesic Plaster were mainly involved in regulating the "immune-inflammation" balance of the body and maintaining the homeostasis of material and energy metabolism， blood circulation， and nervous system functions， and they were closely related to the efficacy of this prescription in clearing heat， reducing detumescence， and relieving pain. Among them， the heat clearing group of Detumescence Analgesic Plaster had the functions of heat clearing， detoxifying， antibacteria， and anti-inflammation. The biological function of its key effect target group was related to correcting the imbalance of "immune-inflammation" induced by pathogens. The detumescence group of Detumescence Analgesic Plaster had the functions of reducing water and swelling and resolving hard lumps， and the biological function of its core effect target group was related to improving microcirculation disturbance. The pain relieving group of Detumescence Analgesic Plaster had the functions of removing stasis， promoting blood circulation， and relieving pain， and its core effect target group was related to correcting the nervous system and the disorder of material and energy metabolism. ConclusionThe heat clearing， swelling reducing， and pain relieving effects of Detumescence Analgesic Plaster may be closely related to its act on related candidate targets， so as to correct the imbalance of "nerve-immunity-vascular-axis"， regulate neuronal excitability and inflammatory response， and intervene in material and energy metabolism. The relevant research results lay a theoretical foundation for clarifying the advantages of Detumescence Analgesic Plaster and assisting its clinical precise positioning.

Objective To explore the causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus(iNPH)using two-sample bidirectional Mendelian randomization.Methods The exposure data including 8 sleep phenotypes used in this study were obtained from GWAS catalog,FinnGenR10 and MRCIEU GWAS.The outcome data for idiopathic normal-pressure hydrocephalus were obtained from FinnGen R10.We used the inverse-variance weighted(IVW)method to perform the principal analyses.Cochrane Q-statistics test was used to assess the heterogeneity and MR Egger-intercept test performed to evaluate the pleiotropy for sensitivity analyses.Results IVW result showed that frequent daytime nap was associated with higher odds of iNPH(OR=3.3393,95 CI%:1.0646-10.4742,P=0.0270).Cochrane Q-statistics test and MR Egger-intercept test showed that the MR analysis had no pleiotropy or heterogeneity(P>0.05).The external validation reproduced this result(OR=2.5660,95 CI%:1.1680-5.6373,P=0.0189;OR=4.0424,95 CI%:1.5709-10.4024,P=0.0038).Reverse Mendelian randomization suggested that iNPH did not have significant impact on sleep phenotype.Conclusion The frequency of daytime naps is causally associated with iNPH,and reducing the frequency of weekly daytime naps can reduce the risk of iNPH in the elderly population.

Objective To explore the causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus(iNPH)using two-sample bidirectional Mendelian randomization.Methods The exposure data including 8 sleep phenotypes used in this study were obtained from GWAS catalog,FinnGenR10 and MRCIEU GWAS.The outcome data for idiopathic normal-pressure hydrocephalus were obtained from FinnGen R10.We used the inverse-variance weighted(IVW)method to perform the principal analyses.Cochrane Q-statistics test was used to assess the heterogeneity and MR Egger-intercept test performed to evaluate the pleiotropy for sensitivity analyses.Results IVW result showed that frequent daytime nap was associated with higher odds of iNPH(OR=3.3393,95 CI%:1.0646-10.4742,P=0.0270).Cochrane Q-statistics test and MR Egger-intercept test showed that the MR analysis had no pleiotropy or heterogeneity(P>0.05).The external validation reproduced this result(OR=2.5660,95 CI%:1.1680-5.6373,P=0.0189;OR=4.0424,95 CI%:1.5709-10.4024,P=0.0038).Reverse Mendelian randomization suggested that iNPH did not have significant impact on sleep phenotype.Conclusion The frequency of daytime naps is causally associated with iNPH,and reducing the frequency of weekly daytime naps can reduce the risk of iNPH in the elderly population.

Objective:To evaluate the efficacy and safety of domestic recombinant human chorionic gonadotropin (r-hCG) for injection in Chinese women undergoing assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled clinical trial, the infertile women with normal ovarian reserve who received COH in seven reproductive medical centers from July 2017 to October 2018 were randomly divided into two groups: experimental group (domestic r-hCG, n=112) and control group (imported r-hCG, n=116). Interactive web response system was used to randomize. The total number of oocytes obtained, cleavage cells, two pronuclei fertilization, mid-division oocytes rate, positive serum hCG rate, early embryo loss rate, clinical pregnancy rate, sustained pregnancy rate and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were (12.1±5.6) and (12.0±6.7) respectively, with no statistically significant difference ( P>0.05). There were no significant differences in the rate of mid-division oocytes, the number of cleavage cells, the number of double pronuclear fertilization, the positive rate of serum hCG during the transplantation cycle, the loss rate of early embryo, the clinical pregnancy rate, and the sustained pregnancy rate between the two groups (all P>0.05), and the 90% confidence interval ( CI) of the difference between the two groups fell within the preset equivalence threshold (-3, +3). The difference in immunogenicity assessment between the two groups was not statistically significant ( P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported r-hCG. Conclusion:In the COH cycle of Chinese infertile women with normal ovarian reserve, the effectiveness and safety of domestic r-hCG are equivalent to imported r-hCG.

Objective:To evaluate the efficacy and safety of domestic recombinant human chorionic gonadotropin (r-hCG) for injection in Chinese women undergoing assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled clinical trial, the infertile women with normal ovarian reserve who received COH in seven reproductive medical centers from July 2017 to October 2018 were randomly divided into two groups: experimental group (domestic r-hCG, n=112) and control group (imported r-hCG, n=116). Interactive web response system was used to randomize. The total number of oocytes obtained, cleavage cells, two pronuclei fertilization, mid-division oocytes rate, positive serum hCG rate, early embryo loss rate, clinical pregnancy rate, sustained pregnancy rate and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were (12.1±5.6) and (12.0±6.7) respectively, with no statistically significant difference ( P>0.05). There were no significant differences in the rate of mid-division oocytes, the number of cleavage cells, the number of double pronuclear fertilization, the positive rate of serum hCG during the transplantation cycle, the loss rate of early embryo, the clinical pregnancy rate, and the sustained pregnancy rate between the two groups (all P>0.05), and the 90% confidence interval ( CI) of the difference between the two groups fell within the preset equivalence threshold (-3, +3). The difference in immunogenicity assessment between the two groups was not statistically significant ( P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported r-hCG. Conclusion:In the COH cycle of Chinese infertile women with normal ovarian reserve, the effectiveness and safety of domestic r-hCG are equivalent to imported r-hCG.

Excessive theta (θ) frequency oscillation and synchronization in the basal ganglia (BG) has been reported in elderly parkinsonian patients and animal models of levodopa (L-dopa)-induced dyskinesia (LID), particularly the θ oscillation recorded during periods when L-dopa is withdrawn (the off L-dopa state). To gain insight into processes underlying this activity, we explored the relationship between primary motor cortex (M1) oscillatory activity and BG output in LID. We recorded local field potentials in the substantia nigra pars reticulata (SNr) and M1 of awake, inattentive resting rats before and after L-dopa priming in Sham control, Parkinson disease model, and LID model groups. We found that chronic L-dopa increased θ synchronization and information flow between the SNr and M1 in off L-dopa state LID rats, with a SNr-to-M1 flow directionality. Compared with the on state, θ oscillational activity (θ synchronization and information flow) during the off state were more closely associated with abnormal involuntary movements. Our findings indicate that θ oscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1 θ oscillation may participate in the induction of dyskinesia.

Objective To investigate the mechanism of improvement of gait behavior in PD rat models by low frequency electrical stimulation of pedunculopontine tegmental nucleus (PPTN) by optogenetics method. Methods (1) Twenty-four healthy adult male SD rats were randomly divided into a sham-operated group 1, a lesion group 1 and a photoactivation group (n=8); normal saline was injected into the right medial frontal tract (MFB) of the sham-operated group 1; 6-hydroxydopamine (6-OHDA) was injected into the lesion group 1 and photoactivation group to induce PD models; two weeks after modeling, injection of adeno-associated virus hsynapsin-ChR2-mcherry into the right PPTN of the three groups was performed, and the photoactivation group received blue-ray stimulation by implanting optical fibers into the PPTN at the same time. (2) Twenty-four healthy adult male SD rats were randomly divided into a sham-operated group 2, a lesion group 2 and a photoinhibition group (n=8);normal saline was injected into right MFB of the sham-operated group 2; 6-OHDA was injected into the lesion group 2 and photoinhibition group to induce PD models; two weeks after modeling, injection of adeno-associated virus hsynapsin-NpHR-mcherry into the right PPTN of the three groups was performed, and the photoinhibition group received yellow-ray stimulation by implanting optical fibers into the PPTN at the same time. (3) Three weeks after injection of adeno-associated virus, Catwalk gait analysis was used to assess the behavioral ability of rats in each group. Results (1) As compared with the sham-operated group 1, lesion group 1 had significantly increased front claw spacing and back front claw spacing, and significantly decreased stride length and pressure of damaged lateral and contralateral limbs, and significantly decreased swing speed of contralateral limb (P<0.05); as compared with those in the lesion group 1, the front claw spacing and back claw spacing were significantly shortened, and stride length and pressure of damaged lateral and contralateral limbs were statistically increased in the photoactivation group (P<0.05). (2) As compared with the sham-operated group 2, lesion group 2 had significantly increased front claw spacing and back front claw spacing, significantly decreased stride length of damaged lateral limb, and significantly decreased pressure and swing speed of damaged lateral and contralateral limbs (P<0.05); no significant differences were noted on the front claw spacing and back front claw spacing, pressure and swing speed of damaged lateral and contralateral limbs between lesion group 2 and photoinhibition group (P>0.05). Conclusion The mechanism of low frequency electrical stimulation of PPTN improving gait behavior of PD rat models is related to activation of PPTN neurons.

Objective To evaluate the effects of body position and cuffed endotracheal tube (cETT) position on the intracuff pressure during tonsillectomy in the pediatric patients.Methods Sixty pediatric patients,aged 3-12 yr,scheduled for elective tonsillectomy under general anesthesia,were divided into group A and group B using a random number table,with 30 patients in each group.The cETTs were placed on one side of the blade of Davis retractor in group A.The cETTs were placed between the blade of Davis retractor and the body of tongue in group B.The intracuff pressure was recorded when the head was in the neutral position (T1),after changing to the head back position (T2) and when the retractor was placed for operation (T3).Results The intracuff pressure was significantly higher at T2 than at T1 in the two groups (P＜0.01).The intracuff pressure was significantly higher at T3 in group A and lower at T3 in group B than at T2 (P＜0.01).Compared with group A,the intracuff pressure was significantly decreased at T3 (P＜0.01),and no significant change was found in the intracuff pressure at T1,2 in group B (P＞0.05).Conclusion The intracuff pressure is affected by body position and cETT position during tonsillectomy in the pediatric patients,and routine monitoring of the intracuff pressure is recommended.