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.

Objective To use bioinformatics analysis to identify the key genes and signaling pathways involved in cardiac dysfunction after acute ischemic stroke.Methods The GSE102558 dataset was downloaded from the Gene Expression Omnibus(GEO)database,and genes with values of P<0.05 and|log2FC|>0.6 were identified as being differentially expressed.The MCODE plugin in Cytoscape software performed a functional module analysis of the protein-protein interaction(PPI)network,while the CytoHubba plugin screened for core genes.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were also performed.A middle cerebral artery occlusion model was constructed to verify core gene expression using real-time PCR.Results Among the screened differential genes,385 were upregulated and 354 were downregulated.The top ten core genes were Col1a1,Col1a2,Col3a1,Fbn1,Postn,Col5a1,Mmp3,Eln,Acta2,and Timp3.The GO enrichment mainly involved the extracellular matrix,the collagen fiber tissue,vascular development,and protease binding.KEGG was mainly enriched in protein digestion and absorption,the relaxin pathway,advanced gly-cation end products-receptor for advanced glycation end products,and platelet activation.Real-time PCR verified that Col3a1and Postn expressions decreased in the heart tissue after acute ischemic stroke.Conclusion Col3a1and Postnexpressions may be closely associ-ated with cardiac dysfunction occurrence and development after acute ischemic stroke.

Objective:To investigate effect of trimetazidine(TMZ)on immune function of Streptococcus pneumoniae(SP)pneumonia rats through cyclic guanylate adenylate synthase(cGAS)-stimulator of interferon gene(STING)pathway.Methods:Rats were randomly separated into model group,TMZ group and DMXAA group(cGAS-STING signaling pathway activator).SP pneumonia rat model was replicated by intranasal instillation of SP,while rats in control group were infused with an equal amount of physiological saline.ELISA was applied to detect IL-1β and IL-10 levels.Flow cytometry was applied to detect CD4+T and CD8+T levels.Spleen and thymus indexes of rats in each group were compared.Transmission turbidity method was applied to detect IgG and IgA levels.HE staining was applied to observe pathological changes in lung tissue.Western blot was applied to detect cGAS-STING pathway proteins expressions.Results:Compared with control group,rats in model group showed an increase in alveolar wall and lung interstitium,accompanied by edema,bleeding and inflammatory cell infiltration,IL-1β,CD8+T cells levels,lung tissue pathological injury score,cGAS,STING expressions were increased,IL-10,CD4+T cells levels,CD4+T/CD8+T,spleen and thymus indexes,IgG,IgA levels were decreased(P<0.05).Compared with model group,rats in TMZ group showed reduced thickening of alveolar walls,great improve-ment in alveolar structure,and less infiltration of inflammatory cells,IL-1β,CD8+T cells levels,lung tissue pathological injury score,cGAS,STING expressions were decreased,IL-10,CD4+T cells levels,CD4+T/CD8+T,spleen and thymus indexes,IgG,IgA levels were increased(P<0.05).Compared with TMZ group,IL-1β,CD8+T levels,pathological injury score of lung tissue,cGAS and STING expressions in DMXAA group were increased,while IL-10,CD4+T cells levels,CD4+T/CD8+T,spleen and thymus index,IgG and IgA levels were decreased(P<0.05).Conclusion:TMZ may inhibit inflammation by inhibiting cGAS-STING signaling pathway,and enhance immune function of rats with SP pneumonia.

Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

Objective:To examine the potential of combining the blood urea nitrogen(BUN)/albumin(ALB)ratio(BAR)with soluble growth stimulation expressed gene 2(sST2)as an early warning indicator for myocardial injury in elderly patients with sepsis in the emergency intensive care unit(EICU).Methods:The clinical data of elderly patients with sepsis admitted to the EICU of the Emergency Medicine Department at Harrison International Peace Hospital of Hebei Medical University from August 2018 to August 2022 were prospectively analyzed.The patients were divided into two groups based on the presence or absence of myocardial injury: the myocardial injury group and the non-myocardial injury group.The general clinical data and laboratory indexes of the two groups were compared, and the BAR was calculated.The correlation between BAR and myocardial injury in elderly patients with sepsis was analyzed.Binary Logistic regression analysis was used to identify the risk factors for myocardial injury in elderly patients with sepsis in the EICU.MedCalc software was employed to determine the early warning value of the combined sST2 and BAR for myocardial injury in elderly patients with sepsis in the EICU.Results:A total of 165 cases were analyzed, with 106 cases(64.24%)showing myocardial injury.It was found that elderly sepsis patients with lung and abdominal infection were more likely to experience myocardial injury( P<0.05 for all).In comparison to the group without myocardial injury, the levels of inflammatory markers such as white blood cell count(WBC), neutrophil to lymphocyte ratio(NLR), lactic acid, and procalcitonin(PCT), as well as combined markers BAR and sST2, were higher in elderly sepsis patients with myocardial injury upon admission.Correlation analysis results revealed significant positive correlations between BAR and lactic acid, PCT, and C-reactive protein(CRP)within 24 hours of admission to EICU in elderly sepsis patients with myocardial injury.Among these correlations, the strongest was observed between BAR and PCT( r=0.417, P<0.001).Additionally, BAR exhibited a positive correlation with acute physiology and chronic health evaluation scoring system(APACHEⅡ)scores( r=0.241, P=0.002).Furthermore, BAR showed positive correlations with myocardial injury markers sST2 and cTnI( r=0.327, 0.307, P<0.05 for all).Logistic regression analysis revealed that septic shock( OR=2.406, P=0.008), decreased left ventricular ejection fraction(EF)( OR=0.939, P=0.015), BAR( OR=2.205, P=0.044), lactic acid( OR=1.137, P=0.014), and sST2 elevation( OR=1.016, P=0.020)were identified as independent risk factors for predicting myocardial injury in elderly patients with sepsis.The results of ROC analysis indicated that BAR had a high early warning value for the occurrence of myocardial injury in elderly patients with EICU sepsis[area under curve(AUC)0.651, P<0.05], with an optimal cut-off value of 0.32(sensitivity 77.4%, specificity 60.2%).Furthermore, the combined detection of BAR and sST2 demonstrated a higher early warning value for the occurrence of myocardial injury in elderly patients with sepsis(AUC 0.697, P<0.05).The mortality rate of patients with myocardial injury below a cut-off value of 0.32 was 36.00%(9/25), while the mortality rate of patients with myocardial injury equal to or above 0.32 was 66.67%(54/81).The difference between the two groups was statistically significant( χ2=8.624, P=0.003). Conclusions:Both BAR and sST2 are considered independent risk factors for myocardial injury in elderly patients with sepsis.The combined detection of BAR and sST2 provides a more accurate prediction for the occurrence of myocardial injury in these patients.

Objective:This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma.Methods:The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) .Results:Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration ( P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups ( P>0.05), and the median PFS and OS time were not reached ( P>0.05) . Conclusions:In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

Objective:To explore the significance of CAS-R-2 frameless brain stereotactic apparatus assisted trepanation and drainage in the treatment of hypertensive basal ganglia cerebral hemorrhage.Methods:The clinical data of 60 patients with hypertensive basal ganglia cerebral hemorrhage, who underwent CAS-R-2 frameless brain stereotactic apparatus assisted trepanation and drainage in Beijing Luhe Hospital, Capital Medical University from January 2018 to December 2022, were retrospectively analyzed. The surgical related indexes and adverse reactions were recorded. The patients were followed up for 6 months, and the prognosis was evaluated using the Glasgow outcome score (GOS).Results:A total of 60 cases of CAS-R-2 frameless brain stereotactic apparatus assisted trepanation and drainage were all successfully performed, and the operation time was (53 ± 18) min. There were 2 cases (3.3%) of postoperative puncture path hematoma, which were completely resolved with conservative treatment. The expansion of postoperative intracerebral hematoma was not observed. The drainage tube retention after operation ≤2 d was in 44 cases (73.3%), and the drainage tube retained for 3 to 4 d was in 16 cases (26.7%), all of them had no intracranial infection after operation. Fifteen cases (25.0%) were complicated with severe pneumonia after operation, and 2 cases (3.3%) died due to severe pneumonia combined with multiple organ failure. Follow up at 6 months after operation, 17 cases (28.3%) were good, 19 cases (31.7%) had mild disability, 16 cases (26.7%) had severe disability, 6 cases (10.0%) had vegetative survival status, and 2 cases (3.3%) died.Conclusions:The CAS-R-2 frameless brain stereotactic instrument assisted trepanation and drainage for the treatment of hypertensive basal ganglia cerebral hemorrhage has the characteristics of simple operation, accurate positioning, minimal trauma, and fewer complications. It is a safe and effective method for treating hypertensive basal ganglia cerebral hemorrhage.

Objective To investigate the clinical characteristics of 16 patients with connective tissue diseases associated interstitial lung disease(CTD-ILD)complicated with lung cancer,and to improve the cognition of the disease.Methods Clinical data of 16 patients diagnosed as CTD-ILD associated with lung cancer,who were admitted to our center,were retrospectively analyzed,including general conditions,clinical characteristics,auxiliary examinations,pathological classification of lung cancer,TNM type,treatment and clinical outcome.Results Among the 16 CTD-ILD patients with lung cancer,there were 12 males and 4 females.The mean age at diagnosis of CTD-ILD was(64.7±9.2)years,and the mean age at diagnosis of lung cancer was(66.6±8.7)years.Lung occupying space on imaging(62.5%)was the most common initial symptom in lung cancer patients,followed by cough and phlegm(12.5%)and chest pain(12.5%).Of patients with lung cancer,adenocarcinoma(8 cases,50.0%)was the most common pathological type,followed by small cell lung cancer(4 cases,25.0%).The diagnosis time of CTD-ILD was earlier than that of lung cancer in 8 cases(50.0%),with a median time of 36.0(11.3,57.0)months,followed by 7 cases(43.8%)of CTD-ILD diagnosed with lung cancer at the same time.The diagnosis time of lung cancer was earlier than that of CTD-ILD in 1 case(6.3%).The most common TNM stage for lung cancer was stage Ⅳ(9 cases,56.25%).Sixteen patients were followed up from 1 to 64 months,with a median of 8.5(1.5,14.3)months.Eleven patients(68.8%)died,including 8 patients(72.7%)died of infection and 3 patients(27.3%)died of end-stage lung cancer.Conclusion For CTD-ILD patients,close follow-up and regular imaging monitoring are necessary to help early detection of lung cancer and improve prognosis.