In this report, the protective effect and molecular mechanism of Chaihu Shugan San-containing serum on corticosterone(CORT)-induced mitochondrial damage in pheochromocytoma(PC12) cells was studied based on CORT-induced rat PC12 cell model. The cultured cells were divided into five groups: blank control group, CORT group(400 μmol·L~(-1) CORT), Chaihu Shugan San-containing serum group(400 μmol·L~(-1) CORT + 10% Chaihu Shugan San-containing serum), control serum group(400 μmol·L~(-1) CORT + 10% control serum), and fluoxetine group(400 μmol·L~(-1) CORT + 10% fluoxetine-containing serum). The study was carried out by cell activity detection, mitochondrial morphology observation, membrane potential measurement, energy metabolism analysis, and mitochondrial dynamics-related protein detection. The results showed that CORT treatment significantly reduced the survival rate of PC12 cells, altered mitochondrial morphology, and decreased mitochondrial membrane potential and adenosine triphosphate(ATP) synthetic rate. Both Chaihu Shugan San-and fluoxetine-containing serum significantly increased the survival rate of CORT-treated PC12 cells and the ATP synthetic rate in the mitochondria. Unlike fluoxetine, Chaihu Shugan San-containing serum significantly inhibited the decrease in mitochondrial membrane potential caused by CORT and increased the oxygen consumption rate(OCR) values of both mitochondrial maximum respiration and reserve respiration capacity. Western blot analysis showed that CORT induced upregulated protein expressions of dynamin-related protein 1(Drp1) and peroxisome proliferator-activated receptor gamma co-activator 1α(PGC-1α) in PC12 cells and specific protein expression of optic atrophy protein 1(OPA1), yet it repressed the protein expressions of silent information regulator 1(SIRT1) and mitochondrial fusion protein 1(Mfn1) in PC12 cells. Both Chaihu Shugan San-and fluoxetine-containing serum significantly inhibited the protein expression of Drp1. However, only Chaihu Shugan San-containing serum could significantly inhibit the CORT-induced upregulation protein of PGC-1α. RESULTS:: herein suggest that Chaihu Shugan San-containing serum can alleviate CORT-induced damage in PC12 cells, which may be related to the mitochondrial fragmentation/lipid peroxidation protection by Drp1 inhibition, as well as mitochondrial dynamics and energy metabolism mediated by PGC-1α/SIRT1 signaling pathway.
Animals ; PC12 Cells ; Rats ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Corticosterone/adverse effects* ; Membrane Potential, Mitochondrial/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Protective Agents/pharmacology* ; Cell Survival/drug effects*

BACKGROUND: In response to growing concerns about the health effects of quasi-millimeter waves (qMMW) used in 5th-generation wireless systems, conservative whole-body exposure thresholds based on indirect evidence have been proposed. The guidelines define a whole-body average specific absorption rate (WBA-SAR) of 4 W/kg which causes a 1 °C increase in core temperature, as the operational threshold for adverse health effects. To address the lack of direct evidence, we recently reported that a 30-minute exposure to qMMW at 4.6 W/kg resulted in a 1 °C increase in rat core temperature. Here, we further analyzed the near-threshold stress response for the first time, using biological samples from the aforementioned and additional experiments. METHODS: A total of 59 young Sprague-Dawley rats (240-322 g) were exposed to 28 GHz for 40 minutes at WBA-SARs of 0, 3.7, and 7.2 W/kg, under normal (22.5 °C, 45-55% humidity), and heat (32 °C, 70% humidity) conditions. Rats were restrained in acrylic holders for dose control. We repeatedly measured serum and urinary biomarkers of stress response, aggregated the data, and analyzed them using a single statistical mixed model to subtract the effects of sham exposure and between-subject variation. RESULTS: Sham exposure induced stress responses, suggesting an effect of restraint. After the subtraction of the sham exposure effect, 28 GHz appeared to induce stress responses as evidenced by elevated serum-free corticosterone 1 or 3 days after the exposure, which was more evident in animals with a change in rectal temperature exceeding 1 °C. Urinary-free catecholamines demonstrated an inhibitory property of 28 GHz frequency exposure on the stress response as evidenced by noradrenaline on the day of exposure. Heat exposure enhanced this effect, suggesting a possible role of noradrenaline in heat dissipation by promoting cutaneous blood flow, a notion supported by the correlation between noradrenaline levels and tail surface temperature, a critical organ for heat dissipation. CONCLUSIONS This study is the first to demonstrate that qMMW whole-body exposure can alter the stress response as indicated by corticosterone and noradrenaline at near-threshold levels. Our findings may provide insight into the biological basis of the whole-body exposure thresholds in the international guidelines.
Animals ; Rats ; Rats, Sprague-Dawley ; Male ; Restraint, Physical ; Stress, Physiological/radiation effects* ; Corticosterone/blood* ; Biomarkers/blood* ; Microwaves/adverse effects*

Empathy is crucial for communication and survival for individuals. Whether empathy in pain contagion shows sex differences and its underlying mechanisms remain unclear. Here, we report that pain contagion can occur in stranger female rats, but not in stranger males. Blocking oxytocin receptors in the anterior cingulate cortex (ACC) suppressed pain contagion in female strangers, while oxytocin administration induced pain contagion in male strangers. In vitro, corticosterone reduces neuronal activation by oxytocin. During male stranger interactions, higher corticosterone decreased oxytocin receptor-positive neuronal activity in the ACC, suppressing pain contagion. These findings highlight the role of oxytocin in pain contagion and suggest that sex differences in empathy may be determined by the balance of oxytocin and corticosterone in the ACC. This study suggests an approach for the treatment of certain mental disorders associated with abnormal empathy, such as autism and depression.
Animals ; Oxytocin/pharmacology* ; Gyrus Cinguli/drug effects* ; Male ; Female ; Corticosterone/pharmacology* ; Empathy/drug effects* ; Sex Characteristics ; Receptors, Oxytocin/antagonists & inhibitors* ; Pain/psychology* ; Rats ; Rats, Sprague-Dawley ; Neurons/metabolism*

Humans ; Female ; Receptors, Estrogen/metabolism* ; Breast Neoplasms/metabolism* ; Receptors, Progesterone/metabolism* ; Immunohistochemistry ; Estrogen Receptor alpha

Background: Metformin has been studied for its anti-proliferative effects on endometrial cells, and it is hypothesized to have a synergistic effect with progestin therapy in suppressing endometrial cell proliferation. This systematic review and meta-analysis aimed to determine the efficacy of adjunctive metformin in the clinical regression of endometrial hyperplasia and early-stage endometrial carcinoma. Methodology: This meta-analysis followed the Cochrane methodology and adhered to the PRISMA 2020 guidelines. Randomized controlled trials (RCTs) were included if they enrolled reproductive-aged women with endometrial hyperplasia (with and without atypia) and endometrial carcinoma who were treated with progestin and metformin. The primary outcome was the complete response rate at 12-16 weeks, and secondary outcomes included relapse rate, clinical pregnancy rate, and live birth rate. Odds ratios (ORs) and 95% confidence intervals (CIs) were used for dichotomous data. Results: Six RCTs were included. The addition of metformin to progestin therapy may increase the complete response rate of endometrial hyperplasia without atypia (OR 5.12, 95% CI 1.17 to 22.41; n=102) and live birth rates (OR 2.51, 95% CI 1.34 to 4.69; n=188) compared to progestin therapy alone, but the certainty of the evidence is low. Metformin did not have a significant effect on the clinical response of endometrial hyperplasia with atypia and endometrial carcinoma, relapse rates, and clinical pregnancy rates. Conclusion Current evidence is uncertain on the potential benefit of metformin with progestin in endometrial hyperplasia and carcinoma. Future high-quality randomized controlled trials with larger sample sizes and longer follow-up periods are needed to support practice recommendations.
Endometrial Hyperplasia ; Endometrial Neoplasms ; Metformin ; Progesterone

OBJECTIVES: Shear wave elastography (SWE) is a novel quantitative elastography technique that can assess the hardness of different tissues. This study introduces a novel shear wave parameter-frequency of mass characteristic (f_mass)-and investigates its correlation, along with other shear wave parameters, with the histopathological features and immunohistochemical (IHC) biomarkers of invasive breast cancer (IBC). The study aims to explore whether SWE can provide useful information for IBC treatment and prognosis. METHODS: With the pathological results as the gold standard, 258 malignant breast lesions were collected, and all patients underwent conventional ultrasound and SWE examinations. The SWE parameters [maximum elastic value (E_max), minimum elastic value (E_min), mean elastic value (E_mean), standard deviation of elastic value of the whole lesion (E_sd)] and f_mass] in the transverse and longitudinal orthogonal sections were measured, and their correlations with the prognostic factors of IBC [including tumor diameters, axillary lymph node (ALN) metastasis, lymphatic vessel invasion (LVI), calcification, histological type, histological grade, and IHC biomarkers (ER, PR, HER-2, Ki-67), and molecular subtypes] were analyzed. The correlations between the SWE parameters of the transverse and longitudinal sections of the tumors with different prognostic factors and the above indicators were analyzed. At the same time, the receiver operating characteristic (ROC) curve was used to analyze the efficacy of f_mass in predicting ER and PR expression. RESULTS: E_mean, E_max, E_sd, and f_mass were correlated with tumor diameters; E_mean, E_max and E_sd were correlated with histological types and histological grades. E_max and E_sd were correlated with ALN metastasis, LVI and pathological types. In the IHC biomarker-labeled masses, f_mass was correlated with ER and PR (both P<0.05), and E_mean, E_max, and E_sd were correlated with HER-2 and Ki-67 (all P<0.05). E_mean, E_max, and f_mass were all correlated with breast cancer subtypes (all P<0.05), and E_mean and E_max were higher in Luminal B [HER-2(+)] breast cancer, while f_mass was lower in HER-2(+) and triple-negative breast cancer. Among the statistically significant prognostic factors, the P values of the transverse sections of the masses were all less than or equal to those of the longitudinal sections. The AUC of f_mass in the transverse sections of the masses for predicting ER and PR expression were 0.73 (95% CI 0.65 to 0.80) and 0.67 (95% CI 0.60 to 0.74), respectively, with the optimal cut-off values being 76.50 and 60.66, the sensitivities being 72.45% and 81.98%, the specificities being 66.13% and 45.35%, and the accuracies being 70.93% and 69.77%, respectively. The AUC of f_mass in the longitudinal sections of the masses for predicting ER and PR expression were 0.74 (95% CI 0.67 to 0.81) and 0.65 (95% CI 0.58 to 0.72), respectively, with the optimal cut-off values being 131.8 and 137.5, the sensitivities being 69.90% and 66.28%, the specificities being 72.58% and 60.47%, and the accuracies being 70.54% and 64.34%, respectively. The f_mass in the transverse sections of the masses was more statistically significant. CONCLUSIONS The poor prognosis factors of IBC are related to high E_mean, E_min, E_max, E_sd, and low f_mass. The f_mass can predict the expression of ER and PR, and the transverse cut data are more meaningful. SWE is helpful for predicting the invasiveness of IBC.
Humans ; Breast Neoplasms/metabolism* ; Female ; Elasticity Imaging Techniques/methods* ; Biomarkers, Tumor/metabolism* ; Middle Aged ; Adult ; Prognosis ; Immunohistochemistry ; Neoplasm Invasiveness ; Receptor, ErbB-2/metabolism* ; Aged ; Lymphatic Metastasis ; Receptors, Estrogen/metabolism* ; Receptors, Progesterone/metabolism* ; Ki-67 Antigen/metabolism*

Objective:To investigate the efficacy and assess the safety of transnasal nebulisation of budesonide in children with adenoid hypertrophy. Methods:Children with adenoid hypertrophy who attended the Children's Hospital of Zhejiang University School of Medicine between December 2021 and December 2022 were randomly assigned to budesonide high-dose group（Group A: budesonide 1 mg/dose + saline nasal rinse）, budesonide low-dose group（Group B: budesonide 0.5 mg/dose + saline nasal rinse）, and control group（Group C: saline nasal rinse）, and each group 20 children were collected separately, The efficacy and safety of transnasal nebulisation of budesonide in children with adenoid hypertrophy were assessed by comparing the symptomatic VAS scores, adenoidal nasopharyngeal lateral radiographs A/N values, nocturnal sleep oximetry（SaO2）, and the incidence of adverse events during the treatment period of 8-week in the three groups. Results:The 8-week baseline differences in adenoid A/N values were statistically different between groups A and B（P<0.001） and A and C（P=0.022）, with the reduced amount in adenoid volume being most pronounced in group A, which differed from the other two groups. With the increase of intervention time, SaO2 levels gradually increased（F=154.725, P<0.001） and VAS scores gradually decreased（F=165.616, P<0.001） in all three groups. After 8 weeks of treatment, there was no statistically significant difference in SaO2 level（P=0.085） between groups A and B. There was a statistically significant difference in VAS total scores between Group A and Group B （P < 0.05） . The improvement of SaO2and total VAS score in group A was higher than that in group B. There was a statistically significant difference in the comparison of SaO2 level and total VAS score between groups A and B, and between groups A and C（P<0.01）; after the intervention of the three groups, showing the greatest improvement of total VAS score and SaO2in the group A, followed by Group B. There was no statistically significant difference in the incidence of adverse events among Groups A, B, and C throughout the trial. Conclusion:The treatment of children with adenoid hypertrophy by intranasal nebulisation of budesonide suspension has good efficacy and safety, which is conducive to reducing the size of adenoids, improving the clinical symptoms of children with adenoid hypertrophy, and improving the SaO2of nocturnal sleep, and it has a certain clinical application value.
Humans ; Budesonide/administration & dosage* ; Adenoids ; Child ; Male ; Female ; Hypertrophy ; Nebulizers and Vaporizers ; Treatment Outcome ; Administration, Intranasal ; Child, Preschool

Embryo implantation involves a complex interaction between the embryo and the endometrium of the mother, the study of which faces a variety of problems. The modeling of endometrial epithelial organoids and endometrial assembloids provides a new way to study the process of embryo implantation in vitro. This paper summarized the latest research progress in embryo implantation, the regulation mechanism of endometrial receptivity by estrogen- progesterone coordination and embryo-derived signals, the establishment of endometrial organoids, and the development and application of endometrial assembloids in the research on mother-embryo interaction, providing new strategies for studying the communication between embryo and maternal uterus during implantation.
Endometrium/physiology* ; Organoids/cytology* ; Embryo Implantation/physiology* ; Female ; Animals ; Progesterone/pharmacology* ; Pregnancy ; Estrogens/metabolism* ; Humans

OBJECTIVE: To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin. METHODS: Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively. RESULTS: Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3β (GSK3β), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05). CONCLUSION Baicalin can promote the development of hippocampal neurons via mTOR/GSK3β signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.
Male ; Animals ; Mice ; Corticosterone ; Fluoxetine/metabolism* ; Depression/chemically induced* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Reproducibility of Results ; Antidepressive Agents/pharmacology* ; Hippocampus ; TOR Serine-Threonine Kinases/metabolism* ; RNA, Messenger/genetics* ; Behavior, Animal ; Disease Models, Animal ; Mammals/metabolism*

OBJECTIVES: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women with reproductive age, which is associated with hyperandrogenism, insulin resistance, and ovulatory dysfunction. Progesterone receptor membrane component 1 (PGRMC1) can mediate progesterone to inhibit the apoptosis of ovarian granulosa cells and the growth of follicles, and to induce glucolipid metabolism disorder in ovarian granulosa cells, which is closely related to the occurrence and development of PCOS. This study aims to determine the expression of PGRMC1 in serum, ovarian tissue, ovarian granulosa cells, and follicular fluid in PCOS patients and non-PCOS patients, analyze the value of PGRMC1 in diagnosis and prognosis evaluation of PCOS, and investigate its molecular mechanism on ovarian granulosa cell apoptosis and glucolipid metabolism. METHODS: A total of 123 patients were collected from the Department of Obstetrics and Gynecology in Guangdong Women and Children Hospital (hereinafter referred to as "our hospital") from August 2021 to March 2022 and divided into 3 groups: a PCOS pre-treatment group (n=42), a PCOS treatment group (n=36), and a control group (n=45). The level of PGRMC1 in serum was detected by enzyme linked immunosorbent assay (ELISA). The diagnostic and prognostic value of PGRMC1 was evaluated in patients with PCOS by receiver operating characteristic (ROC) curve. Sixty patients who underwent a laparoscopic surgery from the Department of Obstetrics and Gynecology in our hospital from January 2014 to December 2016 were collected and divided into a PCOS group and a control group (n=30). The expression and distribution of PGRMC1 protein in ovarian tissues were detected by immunohistochemical staining. Twenty-two patients were collected from Reproductive Medicine Center in our hospital from December 2020 to March 2021, and they divided into a PCOS group and a control group (n=11). ELISA was used to detect the level of PGRMC1 in follicular fluid; real-time RT-PCR was used to detect the expression level of PGRMC1 mRNA in ovarian granulosa cells. Human ovarian granular cell line KGN cells were divided into a scrambled group which was transfected with small interfering RNA (siRNA) without interference and a siPGRMC1 group which was transfected with specific siRNA targeting PGRMC1. The apoptotic rate of KGN cells was detected by flow cytometry. The mRNA expression levels of PGRMC1, insulin receptor (INSR), glucose transporter 4 (GLUT4), very low density lipoprotein receptor (VLDLR), and low density lipoprotein receptor (LDLR) were determined by real-time RT-PCR. RESULTS: The serum level of PGRMC1 in the PCOS pre-treatment group was significantly higher than that in the control group (P<0.001), and the serum level of PGRMC1 in the PCOS treatment group was significantly lower than that in the PCOS pre-treatment group (P<0.001). The areas under curve (AUC) of PGRMC1 for the diagnosing and prognosis evaluation of PCOS were 0.923 and 0.893, respectively, and the cut-off values were 620.32 and 814.70 pg/mL, respectively. The positive staining was observed on both ovarian granulosa cells and ovarian stroma, which the staining was deepest in the ovarian granulosa cells. The average optical density of PGRMC1 in the PCOS group was significantly increased in ovarian tissue and ovarian granulosa cells than that in the control group (both P<0.05). Compared with the control group, the PGRMC1 expression levels in ovarian granulosa cells and follicular fluid in the PCOS group were significantly up-regulated (P<0.001 and P<0.01, respectively). Compared with the scrambled group, the apoptotic rate of ovarian granulosa cells was significantly increased in the siPGRMC1 group (P<0.01), the mRNA expression levels of PGRMC1 and INSR in the siPGRMC1 group were significantly down-regulated (P<0.001 and P<0.05, respectively), and the mRNA expression levels of GLUT4, VLDLR and LDLR were significantly up-regulated (all P<0.05). CONCLUSIONS Serum level of PGRMC1 is increased in PCOS patients, and decreased after standard treatment. PGRMC1 could be used as molecular marker for diagnosis and prognosis evaluation of PCOS. PGRMC1 mainly localizes in ovarian granulosa cells and might play a key role in regulating ovarian granulosa cell apoptosis and glycolipid metabolism.
Child ; Pregnancy ; Humans ; Female ; Polycystic Ovary Syndrome ; Apoptosis ; Granulosa Cells ; Lipid Metabolism ; Membrane Proteins ; Receptors, Progesterone