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.

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.

OBJECTIVE To establish a content determination method for multiple components in Sophora flavescens from different origins and to evaluate its quality by combining with chemometrics. METHODS Thirteen batches （No. K1-K13） of S. flavescens from different origins were selected as test samples. A high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method was established to determine the contents of 12 components， including matrine， oxymatrine， betaine， cytisine， N-methylcytisine， sophoridine， genistein， sophoricoside， sophorone， formononetin， sophorolone Ⅰ and norkurarinone in S. flavescens. Chromatographic separation was performed on a Shim-pack GIST-HP C18 column with a mobile phase consisting of methanol （A） and water containing 0.1% formic acid （B）， using gradient elution at a flow rate of 0.25 mL/min， column temperature of 35 ℃， and an injection volume of 3 μL. Mass spectrometry was conducted using an electrospray ionization source with positive and negative ion scanning. Data were collected in segments using the multiple reaction monitoring mode. Technique for order preference by similarity to ideal solution （TOPSIS） and grey relational analysis （GRA）methods were employed to compare and comprehensively evaluate the 13 batches of S. flavescens from different origins. RESULTS The methodological validation for the content determination met the relevant regulatory requirements. The contents of the 12 components were 490.66-1 231.00， 11 088.10- 18 021.50， 7.91-25.38， 903.97-1 713.64， 336.08-1 485.54，1 065.33-2 075.50， 27.52-71.80， 109.36-517.83， 6 034.55-10 632.73， 21.26-145.35， 814.84-1 911.32， 1 040.87-3 446.37 μg/g）， respectively. TOPSIS results showed that the top 7 samples in Euclidean distance ranking were K6， K12， K11， K3， K5， K10， K13. The GRA results showed that the top 7 samples in the relative correlation ranking were K12， K11， K10， K6， K13， K5， K3. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate， highly sensitive， stable and reliable. Combined with chemometrics methods， it can be used for the quality control and evaluation of S. flavescens. The comprehensive quality of samples K3， K5， K6（ from Hebei）， K10（ from Sichuan）， K11-K13（ from Shanxi）， etc. is relatively superior.

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Objective To compare the efficacy of three different methods in the prevention of adhesion after the HEOS system for different degrees of intrauterine adhesions.Methods 284 patients with mild,moderate and severe intrauterine adhesions,who were treated with the HEOS system,were divided into three groups,the intrauterine device with sodium hyaluronate gel was placed in Group A,Foley water capsule tube with sodium hyaluronate gel was placed in Group B,and sodium hyaluronate gel was placed in Group C only.The recovery of uterine adhesion,improvement of menstruation,endometrial thickness,and adverse reactions were compared among the three groups.Results The mild intrauterine adhesions group showed statistical differences among the three groups(P<0.05).Group A had a higher menstrual improvement rate than Group C(P<0.017),and there was no significant difference in other therapeutic indicators(P>0.017).However,the adverse reaction rate in Group A was also higher than that in Group C(P<0.017).In the moderate intrauterine group,there was a significant difference in the improvement rate of intrauterine adhesions between Group B and the other two groups(P<0.017).Group A and B were higher than Group C in terms of menstrual status,endometrial thickness,and adverse reactions(P<0.017).In severe intrauterine adhesions,Group A had higher efficacy indicators than other groups(P<0.017).Conclusions The curative effect index and adverse reaction rate were analyzed,after operation.For the light,moderate,and severe intrauterine adhesions,sodium hyaluronate gel,Foley water capsule tube with sodium hyaluronate gel,and intrauterine device with sodium hyaluronate gel were the best choice for adhesion.Individual and hierarchical management can achieve good clinical effects,which is worth popularizing.

Objective To analyze the correlation between sympathetic nerve excitability and the occurrence and development of wake-up stroke.Methods A total of 100 patients with acute stroke admitted to our hospital from July 2020 to January 2022 were selected and divided into wake-up stroke group and non-wake-up stroke group according to whether wake-up stroke occurred.Logistic regression model was established to analyze the relationship between sympathetic excitation and the occurrence and development of wake-up stroke.Results Multivariate analysis showed that blood pressure variability,heart rate variability,blood glucose variability,electrolytes disturbance,25-hydroxyvitamin D3,urinary vanilla bitter almond acid,and catecholamine were risk factors for the occurrence and development of stroke after waking up(all P＜0.05).Conclusions Sympathetic nerve excitability is related to the occurrence and development of stroke after waking up.Blood pressure variability,heart rate variability,blood glucose variability,electrolyte disturbance,25-hydroxyvitamin D3,urinary vanilla bitter almond acid and catecholamine are risk factors for the occurrence and development of stroke after waking up.

Objective:To investigate the value of radiomics nomogram based on standardized pre-treatment chest enhanced CT in predicting the mutation status of epidermal growth factor receptor (EGFR) for patients with lung adenocarcinoma.Methods:A retrospective analysis was conducted on pre-treatment chest enhanced CT images and clinical data of 262 patients from the affiliated hospital of Jining Medical University with pathologically proven primary lung adenocarcinoma who received EGFR gene testing, including EGFR wild type ( n=122) and mutant type ( n=140). The patients were divided into training group ( n=183) and testing group ( n=79) according to a ratio of 7∶3 by stratified sampling method. Standardized pre-processed the images, delineated the ROI and extracted the radiomics features. Least absolute shrinkage and selection operator (LASSO) algorithm was used to reduce the dimension and select key features. The standardized radiomics model, clinical model and the combined model were established by Logistic Regression (LR) machine learning method. Calculated the Rad-score and drew the nomogram. ROC curve and Delong were used to evaluate and compare the predictive performance of different models. Results:23 standardized enhanced CT radiomics features and 4 clinical features were selected. The predictive performance of standardized radiomics model was better than that of non-standardized radiomics model [area under curve (AUC): 0.863 vs. 0.805, t=2.19, P<0.05]. The AUCs of the combined model and standardized radiomics model were higher than that of the clinical model (training group: 0.885, 0.863 vs. 0.774, t=3.57, 2.17, P<0.05; testing group: 0.873, 0.829 vs. 0.763, t=2.19, 2.02, P<0.05). The radiomics nomogram was built based on Rad-score, age, sex, smoking history and BMI. Conclusions:The combined model and standardized radiomics model could effectively predict the mutation status of EGFR gene in lung adenocarcinoma patients before treatment, providing valuable clinical insights.

BACKGROUND:Studies have found that glucagon-like peptide-1 and its analogues have a significant neuroprotective effect,and some drugs have been applied to the clinical stage Ⅲ study of Alzheimer's disease.However,the mechanism of its neuroprotective effect is still unclear,which needs to be further explored and clarified. OBJECTIVE:To screen out the genes related to the pathogenesis of Alzheimer's disease and the related targets of semaglutide for the treatment of Alzheimer's disease based on bioinformatics and network pharmacology analyses,to identify the potential target genes by comprehensive analysis of the two and to verify them at the cellular level. METHODS:Using DisGeNET database,differentially expressed genes between Alzheimer's disease patients and healthy population were screened out.The chemical structure formula and two-dimensional structure diagram of semaglutide were obtained using PubChem online database.GO/KEGG enrichment analysis was performed using DAVID online database.A protein-protein interaction network was constructed by using the STRING database.The HPA database was used to determine the distribution characteristics of the target proteins in various human tissues.Finally,western blot was used to detect relevant protein expression in HT22 cells after semaglutide intervention. RESULTS AND CONCLUSION:With the dataset in DisGeNET database,3 374 differentially expressed genes between Alzheimer's disease patients and healthy people were obtained,and meanwhile,101 target genes of semaglutide potential drugs were obtained.There were 23 intersection genes between them.Ten key genes were identified based on the protein-protein interaction network,which were silent information regulator 1(SIRT1),CASP9,CCND1,CASP1,KEAP1,DLG4,CASP4,GRB2,GRIA1,and EDNRA.The results of GO gene functional annotation analysis of key genes showed that the positive regulatory activity of cysteine endopeptidase,the positive regulation of proteolysis,and the positive regulation of cysteine endopeptidase involved the cytoplasmic part of the apoptotic activity process;AMPA glutamate receptor complex,inflammatory complex,CARD domain binding,cysteine endopeptidase activity,and cysteine endopeptidase activity were involved in the apoptotic process.The results of KEGG signaling pathway analysis indicated that colorectal cancer,non-small cell carcinoma,and endometrial carcinoma were related to immune infiltration,inflammation and autophagic apoptosis.In addition,according to the association ranking of key genes and their distribution in different tissues of HPA online database,SIRT1 was identified as the most significant differential gene.The expression level of SIRT1 protein was significantly down-regulated in HT22 cells after β-amyloid protein 1-42 treatment,but it could be significantly increased after being treated with semaglutide.To conclude,SIRT1 may be a target gene for semaglutide in the treatment of Alzheimer's disease.

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 explore the effects of intraspinal blocking analgesia on the delivery quality and puerperal pelvic floor function of primiparas.Methods:A total of 99 primiparas who delivered in the Second People′s Hospital of Wuhu City from January 2021 to April 2022 were enrolled in this study, 54 patients received intraspinal blocking analgesia (study group) and 45 patients received conventional treatment, without intraspinal blocking analgesia (control group). The delivery quality between the two groups was compared, and the pelvic floor function was evaluated and compared by pelvic floor rehabilitation therapy instrument and pelvic floor ultrasound at 6-8 weeks after delivery.Results:Vaginal delivery were successful in both groups. The total labor duration in the study group was longer than that in the control group: (8.03 ± 2.94) h vs. (6.89 ± 3.49) h, there was statistical difference ( P<0.05). The maximum value of pelvic floor rapid contraction stage, rising time and average value of continuous contraction stage in the study group were higher than those in the control group: (32.85 ± 10.13) μV vs. (14.73 ± 3.25) μV, (0.28 ± 0.06) s vs. (0.22 ± 0.05) s, (30.26 ± 5.24) μV vs. (16.74 ± 4.00) μV, there were statistical differences ( P<0.05). There were no statistical differences in other indicators such as the pre-resting stage, rapid contraction phase recovery time and post-resting stage between the two groups ( P>0.05). The rate of pelvic floor class Ⅰ and class Ⅱ muscle abnormalities at 6-8 weeks after delivery in the study group were lower than those in the control group, but there were no statistical differences ( P>0.05). The maximum Valsalva state hiatus area of levator ani muscle, maximum Valsalva state bladder posterior urethral angle, hiatus area of levator ani muscle at rest state and bladder neck degree in the study group were smaller than those in the control group: (19.09 ± 4.82) cm 2 vs. (23.00 ± 5.34) cm 2, (138.59 ± 23.14)° vs. (148.47 ± 20.38)°, (9.96 ± 2.63) cm 2 vs. (11.60 ± 2.75) cm 2, (20.13 ± 4.37) mm vs. (28.05 ± 6.52) mm, there were statistical differences ( P<0.05). Conclusions:Although intraspinal block analgesia can prolong the total labor time of primipara, but it can reduce the damage of pelvic floor function, possibly by increasing systolic period to protect pelvic floor muscles.