ObjectiveTo investigate the potential mechanisms of Zhimu （Anemarrhena asphodeloides）-Huangbai （Phellodendron amurense） medicinal pair in alleviating postmenopausal osteoporosis （PMOP）. MethodsSixty unpregnant female SD rats were randomly divided into five groups， blank group， model group， low-dose Zhimu-Huangbai group， high-dose Zhimu-Huangbai group， and estradiol group， with 12 rats in each group. Except for the blank group， all other groups had their ovaries removed to create PMOP rat models， while the blank group only had the fat tissue around the ovaries removed. One week after the ovarian removal， the low-dose and high-dose Zhimu-Huangbai groups received concentrated solution of Zhimu and Huangbai with 1.8， 7.2 g/（kg·d） via gavage， the estradiol group received estradiol solution 0.09 mg/（kg·d） via gavage， and the blank group and the model group received 10 ml/（kg·d） of normal saline via gavage， once daily for 12 weeks. Before sampling， the body mass of the rats was recorded， and uterine tissue was taken to calculate the uterine index. The levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum were detected by ELISA； micro CT was used to examine the parameters of femoral microstructure， including bone volume/tissue volume （BV/TV）， trabecular number （Tb.N）， trabecular thickness （Tb.Th）， bone mineral density （BMD）， trabecular separation （Tb.Sp）， and cortical bone area （Ct.Ar）. HE staining was used to observe pathological changes in the femur； RT-qPCR was used to detect the mRNA expression of osteogenic-adipogenic differentiation-related factors in femoral tissue， including Runt-related transcription factor 2 （Runx2）， bone morphogenetic protein 2 （BMP-2）， peroxisome proliferator-activated receptor γ （PPARγ）， chemerin and chemokine-like receptor 1 （CMKLR1）. ResultsCompared with the blank group， the model group showed a significant increase in body mass， a significant decrease in the uterine index， BV/TV， Tb.N， Tb.Th and BMD， a significant increase in Tb.Sp， and serum IL-1β， IL-6， and TNF-α levels， a significant reduction of mRNA expression of Runx2 and BMP-2 in bone tissue， and a significant increased mRNA expression of PPARγ， chemerin， and CMKLR1 （P＜0.01）. HE staining revealed that the femoral tissue showed a reduction and sparsity of trabeculae， a significant enlargement of the medullary cavity， and a large number of fat cells. Compared to the model group， the low-dose， high-dose Zhimu-Huangbai groups， and estradiol group showed significant improvements in all the above-mentioned indicators （P＜0.05 or P＜0.01）. HE staining revealed a significant increase in trabeculae， more organized arrangement， and a marked reduction in fat cells. Compared to low-dose Zhimu-Huangbai group， the high-dose Zhimu-Huangbai group exhibited a significant increase in the uterine index and BMD， and a significant reduction in body mass and PPARγ and Chemerin mRNA expression （P＜0.05 or P＜0.01）. Compared to high-dose Zhimu-Huangbai group， the estradiol group showed a decrease in uterine index， BV/TV， Tb.N， Tb.Th， BMD， and BMP-2 mRNA expression， while the levels of IL-1β， TNF-α， and IL-6， as well as Tb.Sp and the mRNA expressions of PPARγ， chemerin， and CMKLR1 increased （P＜0.05 or P＜0.01）. ConclusionThe Zhimu-Huangbai medicinal pair can alleviate PMOP bone loss， and its mechanism of action is related to reducing the levels of inflammatory factors， correcting the disorder of osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells （BMSCs）， and promoting the differentiation of BMSCs into osteoblasts.

Objective:To integrate the real experience of spouse caregivers in the process of caring for dementia patients.Methods:Qualitative researches on the caregiving experience, needs, experience and feelings of spouse caregivers for dementia patients was conducted through computer searches of PubMed, Web of Science, Embase, Cochrane Library, Joanna Briggs Institute (JBI) Evidence Based Healthcare Center Database, CINAHL, PsycINFO, China National Knowledge Infrastructure, Wanfang Database, VIP and China Biology Medicine Disc. The search period was from establishment of the databases to May 2023. The literature was evaluated using JBI quality evaluation criteria for evidence-based health care center quality research, and the results of the included literature were integrated and analyzed by aggregative integration method.Results:A total of 17 articles were included, 62 main research results were extracted and summarized into nine new categories, and three integrated results were synthesized, including increased caring burden accompanied by multiple negative emotions, positive coping with illness, experiencing positive emotions and benefits of caring, multiple unmet needs, and desire for support.Conclusions:It is suggested that medical staff should pay attention to the physical, psychological and social burden of spouse caregivers, use the "Internet +"service and multidisciplinary psychological support therapy to help spouses relieve negative emotions in a timely manner, strengthen contact with the community, build a three-level linkage nursing platform of "hospital community family", and give personalized and substantive help.

Objective:To synthesize the real experiences of medical staff's organizational silence behavior.Methods:A systematic search was conducted in databases including PubMed, Web of Science, Embase, Cochrane Library, CINAHL, EBSCO, ProQuest, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine disc, collecting qualitative studies on medical staff's experiences related to organizational silence behavior. The search period covered the establishment of the databases until June 2024. The quality of the included studies was assessed using the Joanna Briggs Institute's qualitative research quality evaluation standards, and results were integrated using an aggregative synthesis approach.Results:A total of 10 studies were included, with 65 findings summarized into 11 new categories, which were further synthesized into four overarching conclusions: organizational silence is complex, with respect and concern coexisting, many factors contribute to organizational silence, medical staff experience negative emotions as a result of organizational silence, there is a desire for recognition and support.Conclusions:The experience of organizational silence behavior among medical staff is complex. Managers should focus on this issue, encourage individuals to voice their concerns, provide diverse support mechanisms, and enhance positive experiences to reduce the prevalence of organizational silence.

Objective: To investigate the association of parental knowledge and skills in myopia prevention and control with healthy eye behavior in primary school children, so as to provide a basis for accurate family education. Methods: A total of 4 979 students in grades 1-5 from eight elementary schools in Pudong New Area were sampled between October and December in 2022 by using a stratified cluster sampling method. A self administered questionnaire was used to assess healthy eye behavior in primary school children and parental knowledge and skills in myopia prevention and control. The Chi squared test, independent samples t-test and Logistic regression were used to analyse the association between parental knowledge and skills in myopia prevention and control and healthy eye behaviour in primary school children. Results: Parents of primary school children with a high level of knowledge and skills in myopia prevention and control were 50.97% and 56.36%, respectively. The knowlegde entry scores for parents of lower and middle elementary school students were higher than those of parents of upper primary students with respect to their understanding, on the main causes of myopia in their children, the correct knowledge of myopia prevention and control, the role of family members in helping each other to manage and treat myopia in their children and the parents responsibility to teach their children to use their eyes correctly and scientifically (3.05±1.21, 2.97±1.20; 5.92±0.68, 5.83±0.86; 4.46±0.88, 4.40±0.93; 3.88±1.04, 3.72±1.07); all differences were statistically significant (t=2.04, 3.39, 2.00, 4.87, P<0.05). The differences in the scores of parents of primary school children in different grades for all items were statistically significant (t=2.93-7.31, P<0.05) in the skill entries. Parental knowledge levels were poor for items of full scores that assessed the following: knowing the main causes of their childrens myopia, awareness of the correct knowledge of myopia prevention and control measures, awareness of Comprehensive Prevention and Control Strategy for Children and Adolescents with Myopia, and concerning that their childrens future education and employment will be affected by myopia, understanding the responsibility of parents for guiding children to use their eyes scientifically and correctly, with 12.71%, 22.90%, 19.30%, 21.83% and 22.47% respectively. Parental skills were poor for items of full scores that assessed the following:reminding their children to rest their eyes when doing homework, reading or writing, deliberately avoiding mobile phone use when spending time with their children, the number of times which taking children to the hospital for refractive screening in the past year, and giving their children extra learning tasks, with 33.26%, 15.12%, 9.00% and 5.36% respectively. Compared to parental knowledge in myopia prevention and control, parental skills had a more pronounced effect on the four dimensions of healthy eye behavior (reading and writing, screen time, outdoor activities, and sleep duration) among students in different grades (OR=1.41-3.37, P<0.05). Conclusions Parental knowledge and skills in myopia prevention and control are still insafficient, associated with healthy eye behavior in primary school children. There is a need to strengthen accurate health education for parents on the prevention and control of myopia, to cultivate healthy eye behaviour among primary school students and reduce the incidence of myopia among them.

Long non-coding RNAs(lncRNAs)play an indispensable role in the occurrence and development of ovarian cancer(OC).However,the potential involvement of lncRNAs in the progression of OC is largely unknown.To investigate the detailed roles and mechanisms of RAD51 homolog B-antisense 1(RAD51B-AS1),a novel lncRNA in OC,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was performed to verify the expression of RAD51B-AS1.Cellular proliferation,metastasis,and apoptosis were detected using the cell counting kit-8(CCK-8),colony-formation,transwell,and flow cytometry assays.Mouse xenograft models were established for the detection of tumorigenesis.The results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC tissues.RAD51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis.Biogenetics prediction analysis revealed that the only target gene of RAD51B-AS1 was RAD51B.Subsequent gene function experiments revealed that RAD51B exerts the same biological effects as RAD51B-AS1.Rescue experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in vivo.Thus,RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B(Akt)/B cell lymphoma protein-2(Bcl-2)signaling pathway,and these effects may be associated with the positive regulation of RAD51B expression.RAD51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC,and as a potential therapeutic target for disease management.

Objective:To evaluate the relationship between the mechanism underlying the antidepressant effect of S-ketamine and hippocampal gamma-aminobutyric acid B receptor (GABA BR) in mice. Methods:A total of 54 male C57BL/6(B6) mice, aged 8 weeks, weighing 25-30 g, were used in this study. Forty mice were selected to develop the depression model by chronic social defeat stress. Twenty-six depression-susceptible mice were screened out by social avoidance test at day 11 after developing the model and divided into 2 groups ( n=13 each) by a random number table method: depression-susceptible group (Sus group) and depression-susceptible + S-ketamine group (Sus + S-ket group). The remaining 14 mice served as control group (C group). Starting from day 12 after developing the model, S-ketamine 10 mg/kg was intraperitoneally injected every day for 3 consecutive days in Sus+ S-ket group, while the equal volume of normal saline was given instead in C group and Sus group. The open field test was performed at 1 h after the last administration, and the total distance of movement was recorded. The forced swimming test was performed at 1 day after the open field test, and the immobile time was recorded. The sucrose preference test was performed to calculate the proportion of sucrose consumption at 1 day after the forced swimming test. One hour after the end of behavioral test, mice were sacrificed, and the hippocampal tissues were removed. Western blot was used to detect the expression of GABA BR1, GABA BR2, mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), phosphorylated TrkB (p-TrkB), glutamate receptor 1 (GluR1) and postsynaptic dense protein 95 (PSD95). The p-mTOR/mTOR ratio and p-TrkB/TrkB ratio were calculated. The fluorescence intensity of BDNF in hippocampal CA1 region was detected by immunofluorescence. The number of dendritic spines in hippocampal CA1 region was measured by Golgi staining. Results:In the open field test, no statistically significant difference in the total distance was detected among the three groups ( P>0.05). Compared with C group, the immobile time in the forced swimming test was significantly prolonged, the proportion of sucrose consumption was decreased, the expression of hippocampal GABA BR1, GABA BR2, BDNF, GluR1 and PSD95 was down-regulated, and the ratios of p-mTOR/mTOR and p-TrkB/TrkB were decreased, the fluorescence intensity of BDNF and total number of dendritic spines in the hippocampal CA1 region were decreased in Sus group ( P<0.05), and no significant change was found in the parameters mentioned above in Sus+ S-ket group ( P>0.05). Compared with Sus group, the immobile time in the forced swimming test was significantly shortened, the proportion of sucrose consumption was increased, the expression of hippocampal GABA BR1, GABA BR2, BDNF, GluR1 and PSD95 was up-regulated, the ratios of p-mTOR/mTOR and p-TrkB/TrkB were increased, and the fluorescence intensity of BDNF and total number of dendritic spines in the hippocampal CA1 region were increased in Sus+ S-ket group ( P<0.05). Conclusions:The mechanism underlying the antidepressant effect of S-ketamine may be related to up-regulation of hippocampal GABA BR expression, activation of mTOR-BDNF signaling pathway, and improvement in synaptic plasticity in mice.

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.
Animals ; Mice ; Candida albicans ; Candidiasis, Oral/drug therapy* ; Antifungal Agents/pharmacology* ; Hyphae ; Artemisinins/pharmacology*

OBJECTIVE: To explore the effect of thrombocytopenia on the prognosis of patients with septic shock and its mechanism in leading to death. METHODS: A retrospective case-control study was conducted. Patients with septic shock admitted to emergency intensive care unit (EICU) and intensive care unit (ICU) in Peking University People's Hospital from April 1, 2015 to January 31, 2023 were enrolled. Patients were divided into the thrombocytopenia group and the non-thrombocytopenia group, according to whether the minimum platelet count was less than 100×10⁹/L within 24 hours after admission to ICU. The outcome index was the mortality during ICU stay. The baseline data, hospitalization information and laboratory test results of the two groups were compared, and the risk factors of in-hospital death were analyzed by Logistic regression, and the mediation effect was performed by Bootstrap method. RESULTS: A total of 301 patients with septic shock were enrolled, of which 172 (57.1%) had thrombocytopenia and 129 (42.9%) did not. There were significant differences between the two groups in age, mortality, disseminated intravascular coagulation (DIC), continuous renal replacement therapy, and level of creatinine, urea nitrogen, total bilirubin, white blood cell count, lymphocyte count, prothrombin time (PT) and activated partial thromboplastin time (APTT). Univariate Logistic regression analysis showed thrombocytopenia [odds ratio (OR) = 4.478], continuous renal replacement therapy (OR = 4.601), DIC (OR = 6.248), serum creatinine (OR = 1.005), urea nitrogen (OR = 1.126), total bilirubin (OR = 1.006) and PT (OR = 1.126) were risk factors of death during hospitalization in patients with septic shock (all P < 0.05). Multivariate Logistic regression analysis showed that thrombocytopenia [OR = 3.338, 95% confidence interval (95%CI) was 1.910-5.834, P = 0.000], continuous renal replacement therapy (OR = 3.175, 95%CI was 1.576-6.395, P = 0.001) and PT (OR = 1.077, 95%CI was 1.011-1.147, P = 0.021) were independent risk factors for in-hospital mortality in patients with septic shock. Mediation analysis showed that 51% of the deaths due to thrombocytopenia in patients with septic shock were due to coagulopathy. CONCLUSIONS Thrombocytopenia is a powerful predictor of death in septic shock patients, and half of all thrombocytopenia-related deaths may be due to abnormal coagulation function.
Humans ; Shock, Septic ; Retrospective Studies ; Case-Control Studies ; Hospital Mortality ; Prognosis ; Thrombocytopenia ; Intensive Care Units ; Bilirubin ; Nitrogen ; Urea ; Sepsis

Objective: To explore the correlation between different nutritional status and depressive symptoms among adolescents, so as to provide a theoretical basis for targeted improvement of nutritional status and depressive symptoms in adolescents. Methods: A total of 8 102 adolescents aged 12-17 years in Shanghai, Urumqi, Changsha and Kunming were selected by random cluster sampling. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale(CES-D). Height and weight were measured. Kruskal Wallis H test, Chi square test and ordinal Logistic regression were used to analyze the relationship between nutritional status and depressive symptoms in adolescents. Results: The overall detection rate of depressive symptoms in adolescents was 25.6%, with girls (30.1%) higher than that of boys (21.1%) ( χ 2=87.60, P <0.01). There were statistically significant differences in the scores of depressive symptoms among girls with different nutritional status ( Z =8.34, P <0.05). The detectable rate of depressive symptoms increased with BMI among girls( χ 2 trend =6.04, P <0.05). After controlling for confounding factors, ordinal Logistic regression showed that the obese girls had higher risks in depressive symptoms detection compared with normal weight girls ( OR=1.45, 95%CI=1.10-1.91, P <0.05). Conclusion The nutritional status of girls is better than boys, but the prevalence of depressive symptoms is higher than boys. The risk of depressive symptoms in girls increases with BMI.

Objective: To analyze the correlation between physical activity and depressive symptoms in adolescents, so as to provide a reference for the early prevention of depression among adolescents. Methods: Using a random cluster sampling method, 8 102 adolescents from Shanghai, Urumqi, Changsha and Kunming were investigated via the Physical Activity Assessment Questionnaire of Chinese Children and Adolescents aged 7 to 18 and the Center for Epidemiologic Studies Depression Scale (CES-D) for physical activity and depressive symptoms. Multivariate Logistic regression analysis was used to analyze the correlation between physical activity and depressive symptoms in adolescents. Results: The proportion of adolescents who met moderate to vigorous physical activity (MVPA) standard was 37.0%, and the detection rate of depressive symptoms was 25.6%. The detection rate of depressive symptomsin compliant with MVPA standard group was significantly lower than that in non compliant group among different age and gender( χ 2=7.62-34.54, P <0.05). Adolescents with severe depressive symptoms had high light intensity physical activity(LPA) duration and low vigorous intensity physical activity(VPA) duration, while adolescents with mild depressive symptoms or asymptomatic adolescents had higher MVPA duration. There were differences in LPA and VPA among adolescents with different levels of depressive symptoms in the overall sample, and the differences were still significant among girls, middle school and statistically significant differences in LPA, moderate intensity physical activity(MPA), MVPA were also found among the high school subgroup. However, differences only in LPA were observed among boys with different levels of depression( H=46.48, 10.31, 25.02, 29.54, 30.25, 19.80, 22.20, 9.54, 8.62, 18.06, P <0.05). Multivariate Logistic regression model showed that gender and duration of MVPA were significantly related to risk of depressive symptoms( OR=1.56, 1.42, P <0.05). Conclusion Physical activity among adolescents is significantly related to depressive symptoms. MVPA may be an effective measure to reduce the degree of depressive symptoms.To improve the physical health and prevent depression among adolescents, it is important to choose appropriate physical activity types and effectively increase the duration of MVPA.