BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Objective To investigate the effect of midazolam on neuronal damage in ischemic stroke （IS） rats and its regulatory effect on PTEN-induced putative kinase 1 （PINK1）/E3 ubiquitin ligase （PARKIN） signaling pathway. Methods An IS rat model was established using arterial occlusion method. The rats with successful model were randomly divided into IS group, drug-low, medium, high-dose （drug-L, M, H, 30, 60, 90 mg/kg midazolam） groups, drug-H+autophagy inhibitor 3-MA group （90 mg/kg midazolam+30 mg/kg 3-MA）, and rats with only isolated blood vessels were used as sham surgery groups. Each group received corresponding doses of drugs or physiological saline intervention, and the neurological function scoring, brain histopathology, neuronal apoptosis, ultrastructure, and expression of PINK1, PARKIN, microtubule-associated protein 1 light chain 3 （LC3）, and P62 protein in mitochondria were detected. Results Compared with the IS group, the pathological damage of the drug-L group, drug-M group, and drug-H group was improved, and autophagosomes showed an increasing trend, the expression of PINK1, PARKIN, and LC3 proteins increased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously decreased in a dose-dependent manner （P<0.01 or P<0.001）; compared with the drug-H group, the pathological damage in the drug-H+3-MA group increased and autophagosomes decreased, the expression of PINK1, PARKIN, and LC3 proteins decreased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously increased （P<0.001）. Conclusion Midazolam induced mitochondrial autophagy in IS rats by activating the PINK1/PARKIN signaling pathway, neuronal apoptosis was reduced and neuronal damage were improved in IS rats.

ObjectiveTo analyze the epidemiological characteristics of influenza virus in severe acute respiratory tract infection (SARI) cases in Jingzhou City, so as to provide a scientific basis for the formulation of influenza prevention and control policies in Jingzhou City. MethodsSARI surveillance was carried out in two sentinel hospitals in Jingzhou City from 2018 to 2023. Respiratory tract samples were collected from cases and influenza virus nucleic acid was measured using real-time fluorescent polymerase chain reaction (RT-PCR). ResultsA total of 2 603 SARI samples were tested from 2018 to 2023, and 338 samples were positive for influenza virus nucleic acid, with a detection rate of 12.99%. The highest positive detection rate was 20.22% in 2019, followed by 14.29% in 2022, and the lowest detection rate was 7.75% in 2020. There were significant differences for the positive detection rates of influenza in each monitoring year (χ²=30.386, P<0.001). There were epidemic peaks in the five surveillance years from 2018 to 2023 except 2020. There were winter epidemic peaks during 2018‒2019 and 2021‒2022, and an obvious summer epidemic peak was also observed from 2019 to 2022. H1N1, H3N2, B-Victoria and B-Yamagata were alternately prevalent in the six surveillance years. In 2019, H1N1, H3N2 and B-Victoria were alternately prevalent with time progress, in 2021 only B-Victoria was prevalent, and in 2022 H3N2 and B-Victoria were prevalent. There was no statistically significant difference for the positive detection rates of influenza virus between different genders (χ²=0.178, P=0.673). Among the four age groups, the positive rate of influenza virus in the age group of 15‒<25 years old was the highest (40.91%), followed by the age group of 25‒<60 years old (21.31%). There were statistically significant differences for the positive rates of influenza virus among different age groups (χ²=24.496, P<0.001). ConclusionThe surveillance of SARI cases in Jingzhou City could serve as an effective supplement to the surveillance of ILI in sentinel hospitals. It is suggested to expand the surveillance scope, strengthen public education and outreach on the prevention and control of respiratory diseases, thereby providing a scientific basis for influenza prevention and control.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Ethanol (EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin (CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4 (CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor-κB p65 (NF-κB) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.
Ethanol/toxicity* ; Animals ; Gastric Mucosa/metabolism* ; Signal Transduction/drug effects* ; Oxidative Stress/drug effects* ; Capsaicin/pharmacology* ; Male ; NADPH Oxidases/genetics* ; Mice ; Humans ; src-Family Kinases/genetics*

Background The respiratory toxicity of inhaled polyhexamethylene guanidine (PHMG) has been extensively studied since the humidifier disinfectant incident. However, the impacts of inhalation of PHMG on the immune system are not comprehensively studied yet. Objective To explore the effects of inhalation of PHMG disinfectant aerosol on major immune organs and immune cells in mice. Methods Thirty male C57BL/6J mice (6-8 weeks old) were randomly divided into three groups: control, low-dose (0.1 mg·m⁻³ PHMG), and high-dose (1.0 mg·m⁻³ PHMG), with ten mice in each group. The mice were administered by oral-nasal inhalation of PHMG aerosol for 4 h per day, 5 d per week for 4 weeks consecutively. After designed treatment, venous blood was collected from the inner canthus of the eyes of mice and peripheral hematological indicators were measured with a blood analyzer. Then the mice were sacrificed by cervical dislocation and the lung, thymus, spleen, and femur were isolated. Lung, thymus, and spleen were weighed and organ coefficients were calculated, and single cell suspensions of thymus, spleen, and bone marrow were prepared to analyze lymphocytes phenotypes and proportions by flow cytometry. Results The body weight of mice in the high-dose group was lower than that of mice in the control group (P<0.01) from the 7th day of inhalation, and decreased by 15.74% compared with that of mice in the control group at the end of inhalation (P<0.01). The lung coefficients of both the low-dose and high-dose groups were higher than that of the control group (P<0.01), the thymus coefficient of mice in the high-dose group was lower than that of the control group (P<0.05), but the spleen coefficient did not change significantly (P>0.05). Leukocyte count [(1.49±0.22)×10⁹·L⁻¹], lymphocyte count [(0.96±0.36)×10⁹·L⁻¹] and its proportion [(63.13±14.96)%] in the peripheral blood of mice in the high-dose group were lower than those in the control group [(2.69±0.25)×10⁹·L⁻¹, (2.33±0.28)×10⁹·L⁻¹, and (86.23±3.40)%, respectively] (P<0.01), whereas red blood cell count [(12.32±0.46)×10¹²·L⁻¹], hemoglobin count [(175.25±4.65) g·L⁻¹], and hematocrit [(53.55±0.70)%] in the peripheral blood of mice in the high-dose group were higher than those in the control group [(11.11±0.37)×10¹²·L⁻¹, (160.67±4.04) g·L⁻¹, and (45.10±9.75)%, respectively] (P<0.05). Compared with the control group, the proportion of CD4+ CD8+ double-positive T cells decreased (P<0.05), the proportions of CD4+ T cells and CD8+ T cells increased (P<0.05), and the amounts of CD8+, CD4+ CD8+, CD4+, and CD4- CD8- cells decreased (P<0.05) in the thymus of mice of the high-dose group, the proportion of CD4+ T cells in the spleen of the high-dose group increased (P<0.05), the proportions and amounts of T cells, CD4+ T cells, and CD8+ T cells in the bone marrow of the high-dose group increased (P<0.05). Conclusion Inhalation of PHMG may cause thymic atrophy, disrupt T-lymphocyte development, and lead to an imbalance in the number of immune cells in the bone marrow, peripheral blood, and spleen, suggesting that inhalation of PHMG induces immune dysfunction.

Objective:To develop and verify a nomogram to predict disease-free survival(DFS)and overall survival(OS)for patients undergoing cervical cancer surgery,which may provide reference for evaluating the prognosis of cervical cancer patients undergoing surgery.Methods:The clinical,pathological and follow-up data of patients who underwent radical operation for cervical cancer in Xijing Hospital,Air Force Medical University from March 2013 to October 2018 were analyzed retrospectively.Based on Cox regression analysis,Bayesian Informa-tion Criterion(BIC)backward stepwise selection method and R square screening variables,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were used to compare the predictive efficiency of the model,and a nomogram with better predictive efficiency was selected.The consistency index(C-index)and the receiver operating characteristic curve(ROC)were used to test the efficiency of the nomogram.Results:A total of 950 patients with cervical cancer were enrolled in this study.The risk factors for constructing the DFS nomogram were FIGO stage(2018),parametrium invasion,invasion depth,and maximum tumor diameter.The C-index for DFS in the training cohort and the verification cohort were 0.754 and 0.720,respectively.The area under ROC of the training cohort for 1-,3-and 5-years was 0.74(95%CI 0.65-0.82),0.77(95%CI 0.71-0.83)and 0.79(95%CI0.74-0.85),and the areas under ROC of verification cohort 1-,3-and 5-years were 0.72(95%CI 0.58-0.87),0.75(95%CI 0.64-0.86)and 0.72(95%CI 0.61-0.84),respectively.The risk factors for con-structing the OS nomogram were FIGO stage(2018),histological type,LVSI,parametrium invasion,surgical mar-gin,and invasion depth.The C-index for OS in the training cohort and the verification cohort were 0.737 and 0.759,respectively.The area under ROC of the 3-and 5-year training cohort were 0.76(95%CI 0.69-0.83)and 0.78(95%CI 0.72-0.84),and the areas under ROC of verification cohort 3-and 5-years were 0.76(95%CI 0.65-0.87)and 0.79(95%CI 0.69-0.88),respectively.Conclusions:This study is based on real-world big data to construct nomogram of DFS for 1,3,and 5 years and OS for 3,and 5 years for cervical cancer,which have ideal predictive effects and help clinical physicians correctly evaluate the prognosis of cervical cancer surgery patients.It provides strong reference basis for diagnosis,treatment,and prognosis evaluation.

BACKGROUND:There are many kinds of cell media with different components,which have a great influence on cell growth.Several studies in and outside China have used serum-free media containing fetal bovine serum for in vitro amplification culture,but the use of media containing human peripheral blood serum to directionally induce human umbilical cord mesenchymal stem cells to neural stem cells and human peripheral blood serum to promote neural stem cells to differentiate into other nerve cells,so far there are few relevant studies. OBJECTIVE:To observe the feasibility of inducing human umbilical cord mesenchymal stem cells cultured with human peripheral blood serum into neural stem cells. METHODS:(1)Human umbilical cord mesenchymal stem cells were cultured in DMEM/F-12 culture medium containing 10%human peripheral blood serum by volume fraction.Flow cytometry analysis was performed at the third passage to identify surface markers and alizarin red staining was used to detect osteogenic differentiation function.(2)The third-generation human umbilical cord mesenchymal stem cells were induced into neural stem cells using DMEM/F-12 medium containing 0.5%N2,1.5%B27,20 ng/mL basic fibroblast growth factor,and 20 ng/mL epidermal growth factor,and their surface markers were identified.(3)Well-growing human umbilical cord mesenchymal stem cell-derived neural stem cells were taken to prepare a single cell suspension.They were evenly inoculated into 96-well plates and incubated with DMEM/F-12 culture medium containing 10%human peripheral blood serum for 8 days.Then,hematoxylin-eosin staining,microtubule-associated protein 2,and glial fibrillary acidic protein immunofluorescence staining were performed to detect the differentiation of neural stem cells into other neural cells. RESULTS AND CONCLUSION:(1)Human umbilical cord mesenchymal stem cells cultured with human peripheral blood serum grew in a spiral-like pattern and were distributed in multiple layers,with directional arrangement.The surface of human umbilical cord mesenchymal stem cells highly expressed CD44,CD105,CD29,and CD73.Cells stained with alizarin red showed a color reaction.(2)Human umbilical cord mesenchymal stem cells cultured with human peripheral blood serum could be induced to differentiate into neural stem cells,and the surface of neural stem cells was highly expressed with CD44,CD105,CD29,CD73,Nestin,NF-L,and GALC.(3)On day 8 of induced differentiation of neural stem cells,after staining with hematoxylin and eosin,it was found that the protruding protrusions were longer,with more branches and adjacent cells connected,presenting typical neural cell morphology.Immunofluorescence staining for microtubule-associated protein 2 and glial fibrillary acidic protein was positive.It is concluded that human umbilical cord mesenchymal stem cells cultured by human peripheral blood serum can be directly induced to differentiate into neural stem cells.Under the action of human peripheral blood serum,neural stem cells can differentiate into other neural cells as the culture time prolongs.

OBJECTIVE:Exercise intervention is one of the main treatments for fibromyalgia,but there is no consistent conclusion on the choice of different exercise modalities.In this article,a network Meta-analysis was used to comprehensively and quantitatively evaluate the effects of different exercise modalities on fibromyalgia syndrome. METHODS:PubMed,EMbase,Scoups,The Cochrane Library,Web of Science,CNKI,WanFang Database,and China Biomedical Literature Database were searched for relevant literature,with a search timeframe from the establishment of each database to June 2023.The outcome indicators included five continuous variables,including fibromyalgia impact questionnaire-revised(FIQ)scores,visual analogue scale(VAS)scores,quality of life,quality of sleep,and depression.The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of the included literature.RevMan 5.4 software was used to perform effect sizes,subgroup analyses,and sensitivity analyses of the data.Stata 17 software was used to perform reticulation and network Meta-analysis of the data. RESULTS:A total of 13 articles with 14 randomized controlled trials were finally included.The overall methodological quality of the literature was high.The results of traditional Meta-analysis showed that,compared with the control group,exercise therapy significantly improved the FIQ score[standardized mean difference(SMD)=-0.67,95％confidence interval(CI):-0.83 to-0.50,P<0.01],VAS score(SMD=-0.72,95％CI:-0.90 to-0.54,P<0.01),quality of life(SMD=1.03,95％CI:0.45 to 1.61,P=0.000 5),sleep quality(SMD=-0.62,95％CI:-0.98 to-0.25,P=0.001),and depression(SMD=-0.63,95％CI:-1.09 to-0.18,P=0.007).Network Meta-analysis showed that the probability of optimal intervention effect of exercise modalities on FIQ scores was ranked as:mind-body exercise(86.5)>resistance exercise(70.5)>aerobic exercise(41.7);the probability of optimal intervention effect of exercise modalities on VAS scores was ranked as:resistance exercise(85.3)>mind-body exercise(74.3)>aerobic exercise(34.5). CONCLUSION:Exercise therapy significantly improves FIQ scores,VAS scores,quality of life,sleep quality,and depression in patients with fibromyalgia syndrome.Mind-body exercise and resistance exercise are the most effective exercise modalities to reduce FIQ scores and VAS scores in patients with fibromyalgia syndrome.

OBJECTIVE To study and analyze the relationship between serum levels of Endocan,Cyclophilic A (CyPA),and asprosin with the condition severity and cognitive function in patients with obstructive sleep apnea hypopnea syndrome(OSAHS). METHODS From November 2021 to December 2023,99 OSAHS patients who visited our hospital were collected and separated into mild group(n=29),moderate group(n=45),and severe group(n=25) based on the apnea hypopnea index(AHI). ELISA method was applied to detect serum levels of Endocan,CyPA,and asprosin. Multivariate logistic regression was used to analyze the influencing factors of severity of condition. ROC curve was plotted to analyze the diagnostic value of serum Endocan,CyPA,and asprosin for cognitive function in OSAHS patients. Spearman rank correlation was applied to analyze the correlation between serum Endocan,CyPA,asprosin,with severity of condition,cognitive function. RESULTS Compared with the mild group,the serum levels of Endocan,CyPA,and asprosin were obviously increased in the moderate and severe groups(P<0.05),and the serum levels of Endocan,CyPA,and asprosin in the severe group were obviously increased compared to the moderate group(P<0.05). There were statistically obvious differences in AHI,Epworth sleepiness scale(ESS) scores,and some sleep related parameters among the three groups(P<0.05). Further analysis revealed that mean blood oxygen saturation(MSaO2) was a protective factor affecting the severity of condition(P<0.05),while AHI,serum Endocan,CyPA,and asprosin levels were all risk factors affecting the severity of condition(P<0.05). The serum levels of Endocan,CyPA,and asprosin in patients with cognitive impaired were obviously higher than those in patients with normal cognition,and the MoCA score was lower than that in patients with normal cognition(P<0.05). The AUC of serum Endocan,CyPA,asprosin,and combined diagnosis for cognitive impairment in patients was 0.889,0.893,0.861,and 0.974,respectively,and the combined diagnosis was obviously better than individual diagnosis of Endocan(Z=2.832,P=0.005),CyPA(Z=2.907,P=0.004),and asprosin(Z=3.225,P=0.001). Serum Endocan,CyPA,and asprosin were positively correlated with AHI and negatively correlated with MoCA score(P<0.05). CONCLUSION In patients with severe OSAHS and cognitive impairment,serum Endocan,CyPA,and asprosin levels are all increased,and they have certain auxiliary diagnostic value for the severity of condition and cognitive function.