ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

To investigate the role of intestinal fungi in the progression of heart failure (HF) associated with chronic kidney disease (CKD).

Objective To evaluate safety and efficacy of linaclotide combined with polyethylene glycol(PEG)for bowel preparation.Methods A total of 612 patients from Department of Gastroenterology at the Affiliated Hospital of Qingdao University for colonoscopy examination from January to June 2023 were selected.They were divided into group 1(1 L PEG+2 L PEG),group 2(linaclotide+2 L PEG)and group 3(1 L PEG+linaclotide+1 L PEG)by random number table method,with 204 cases in each group.The Ottawa Bowel Preparation Quality Scale(OBPS),the insertion time of colonoscopy,the time of the first defecation,the frequency of defecations,the occurrence of adverse effects and patients'tolerability were compared among the three groups.Results A total of 601 patients completed bowel preparation and accepted colonoscopy.Group 1 exhibited no statistically significant differences to group 2 with regards to OBPS and insertion time.However,Group 2 demonstrated a shorter duration for the time of the first defecation in comparison to both group 1 and group 3(P＜0.05).Group 1 displayed a higher frequency of defecations as compared to Group 2 and Group 3(P＜0.05).The incidence of adverse reactions was significantly lower in group 2 and group 3 than in group 1(P＜0.05).The overall tolerance score of patients in group 1 was low-er than that in group 2 and group 3(P＜0.05).Conclusions The effect of combining 2 L PEG with 290 μg of lina-clotide for bowel preparation before colonoscopy is similar to that of 3 L PEG.It can reduce the incidence of adverse reactions and patients exhibit good tolerance.For patients who are intolerant to a single high-dose administration of PEG,they need divided-dose regimen of 2 L PEG in combination with linaclotide.

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

Objective To explore the effect of ephedrine on airway remodeling and its regulation effect on transfor-ming growth factor-β1(TGF-β1)/Smads pathway in asthmatic mice.Methods All mice were randomly separated into control group,model group,dexamethasone group,ephedrine low-dose group,ephedrine high-dose group,and ephedrine high-dose+TGF-β1 activator group,with 12 mice in each group.Except for the control group,mice in other groups were intraperitoneally injected with 40 μg ovalbumin(OVA)and 2 mg 10％aluminium hydroxide sensitizer to induce asthma models.After 8 weeks,the airway hyperresponsiveness of mice in each group was detec-ted;eosinophils in bronchoalveolar lavage fluid(BALF)were counted;ELISA was applied to detect the levels of interleukin(IL)-4,IL-5,and IL-13 in BALF;hematoxylin-eosin(HE)staining and Masson staining were applied to observe the pathological changes and collagen fiber area of mouse lung tissue;immunohistochemistry was applied to detect the expression of α-smooth muscle actin(α-SMA)protein in mouse lung tissue;Western blot was applied to detect the expression of TGF-β1/Smads pathway related proteins in mouse lung tissue.Results Compared with the control group,the airway hyperreactivity at different doses of methacholine,total area of airway wall(Wat)/perimeter of the basement membrane(Pbm)ratio,collagen fiber area,eosinophil,the contents of IL-4,IL-5,IL-13,the expression of α-SMA,TGF-β1,the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the model group in-creased(P＜0.05),the expression of Smad7 decreased(P＜0.05);compared with the model group,the airway hyperreactivity at different doses of methacholine,Wat/Pbm ratio,collagen fiber area,eosinophil,the contents of IL-4,IL-5,IL-13,the expression of α-SMA,TGF-β1,the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the dexamethasone group,the ephedrine low-dose and high-dose groups decreased(P＜0.05),the expression of Smad7 increased(P＜0.05);compared with the ephedrine high-dose group,the airway hyperreactivity at different doses of methacholine,Wat/Pbm ratio,collagen fiber area,eosinophil,the contents of IL-4,IL-5,IL-13,the ex-pression of α-SMA,TGF-β1,the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the ephedrine high-dose+TGF-β1 activator group increased(P＜0.05),the expression of Smad7 decreased(P＜0.05).Conclusion E-phedrine can improve airway remodeling in asthmatic mice,and its mechanism is related to the regulation of TGF-β1/Smads signaling pathway.

Objective To compare the inhibitory effects of remimazolam and dexmedetomidine on cough during emergence from general anesthesia after thyroid surgery.Methods Patients with 111 cases of thyroid surgery were randomly divided into 3 groups,37 in each group.Group A was given a bolus of 0.1 mg·kg-1 and 0.05 mg·kg-1·h-1 remimazolam intravenous infusion until extubation,group B was given 0.5 μg·kg-1 of the dexmedetomidine over 10 minutes,and group C was given same dose of normal saline.The incidence of cough during emergence from general anesthesia,the moderate and severe cough,the recovery time and extubation time,the Ramsay Sedation Scale(RSS)score,and the heart rate(HR),and mean arterial pressure(MAP)at different time points before and after intervention and before and after extubation were recorded and compared.Results There were significant differences in the incidence of coughing among group A,B and C(37.84％vs.67.57％vs.91.89％,adjusted P＜0.016 7,respectively).The incidence of moderate and severe cough was also lower in group A than in group B and C(8.11％vs.35.14％vs.67.57％,adjusted P＜0.001).The recovery time and extubation time were longer in group B than those of group A and C(adjusted P＜0.001).The RSS scores at the time of extubation and after extubation were higher in group B than in group A and C(adjusted P=0.002 and P=0.007,respectively).After intervention,compared with group C,the HR of group A and B decreased to different degree,and different drugs interacted with time,and the HR of group B patients decreased to a greater extent.Conclusion Remimazolam suppresses the occurrence and reduces the severity coughing during emergence from general anesthesia,and reduce the severity in patients treated with thyroid surgeries.Compared with dexmedetomidine,remimazolam did not prolong recovery time and extubation time,remaining more stable haemodynamics.

Objective:To summarize the clinical characteristics and prognosis of severe infant botulism and evaluate the therapeutic effect of botulinum antitoxin in the pediatric intensive care unit (PICU).Methods:The clinical data of 8 cases diagnosed with infantile botulism were retrospectively analyzed in the PICU of Beijing Children′s Hospital from October 2019 to August 2023. Data of basic demographic information, clinical manifestations, laboratory tests, treatment and prognosis of each child were collected and analyzed using descriptive statistical methods.Results:Eight laboratory-confirmed cases of infant botulism were included in this study, all of which were male infants with an age of 6.0 (3.3,6.8) months. Three of the children were from Inner Mongolia Autonomous Region, 2 of them were from Hebei, and the other 3 were from Beijing, Shandong and Xinjiang Uyghur Autonomous Region, respectively. All the patients were previously healthy. In 4 of these cases, the possible cause was the ingestion of either honey and its products or sealed pickled food by the mother or child before the onset of the disease. The first symptom was poor milk intake (4 cases), followed by shallow shortness of breath (7 cases), limb weakness (7 cases) and so on. The typical signs were bilateral dilated pupils (8 cases) and decreased limb muscle strength (8 cases). The main subtype was type B (7 cases), and only 1 case was classified as type A. Six of the children were treated with antitoxin therapy for a duration of 24 (19, 49) d. Seven of them had invasive mechanical ventilation. All the patients survived upon discharge with a follow-up period of 29 d to 3 years and 8 months. Six patients had fully recovered, and 2 recently discharged patients were gradually recovering.Conclusions:For infants with suspected contact or ingestion of botulinum and presented with bilateral pupillary paralysis, muscle weakness and clear consciousness, the stool should be collected for diagnostic testing using a mouse bioassay as soon as possible. Type B was the most common type. The antitoxin treatment was effectiveness and the prognosis was well.

Objective To compare the efficacy of intravenous thrombolysis combined with intravascular therapy for patients with acute ischemic stroke(AIS)from different treatment opportunities and its impact on prognosis.Methods A total of 180 AIS patients admitted to Wenzhou Central Hospital from July 2021 to September 2023 were selected as study objects,and divided into group A(thrombolysis within 2h),Group B(thrombolysis within 2-3h),group C(thrombolysis within 3-4.5h),group D(thrombolysis within 4.5-6h)and group E(thrombolysis within 6-9h)according to different thrombolysis times after owset.There were 36 cases in each group.All patients received alteplase intravenous thrombolysis combined with intravascular therapy.Vascular recanalization,neurological function,prognosis,ability of daily living and complications were compared among all groups.Results Vascular recanalization rate of five groups had statistical significance(χ2=11.500,P=0.022).Vascular recanalization rate of group E was significantly lower than that of other four groups(P<0.05),and vascular recanalization rate of group D was significantly lower than that of groups A,B and C(P<0.05).After thrombolysis,National Institutes of Health stroke scale(NIHSS)score and modified Rankin scale(mRS)score of patients in all groups were significantly decreased with the extension of time(P<0.05).At different time after thrombolysis,NIHSS score and mRS score in group E were significantly higher than those in other four groups,and NIHSS score and mRS score in group D were significantly higher than those in groups A,B and C(P<0.05).After thrombolysis,Barthel index(BI)of all groups increased significantly with the extension of time(P<0.05).At different time after thrombolysis,BI score of group E were significantly lower than those of other four groups,and BI score of group D were significantly lower than those of groups A,B and C(P<0.05).Within 90 days after thrombolysis,there was no significant difference in the incidence of intracranial hemorrhage,oral hemorrhage,nosocomial infection and cerebral hernia among five groups(χ2=1.356,P=0.852).Conclusion Alteplase intravenous thrombolysis combined with intravascular therapy in AIS patients within 4.5h has better clinical efficacy and better prognosis.

Objective To investigate the effect and mechanism of Zhike Pingchuan Formula on reducing airway inflammation in mice with bronchial asthma(BA).Methods A total of 84 BALB/c mice were randomly separated into the control group,the BA group,the low-dose Zhike Pingchuan Formula group,the high-dose Zhike Pingchuan Formula group,the dexamethasone group,the lipopolysaccharide(LPS)group and the high-dose Zhike Pingchuan Formula+LPS group,with 12 mice in each group.The BA model was constructed in all groups of mice except the control group.After successful modeling,mice were treated with drug administration once a day for 3 weeks.Serum immunoglobulin E(IgE)concentration and levels of interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)in alveolar lavage fluid were detected by enzyme linked immunosorbent assay(ELISA).Pathological changes in lung tissue was detected by HE staining.The bronchial epithelium goblet cell proliferation and mucus secretion were determined by PAS staining.Flow cytometry was used to detect levels of T helper cell 17(Th17)and regulatory T(Treg)cell in mouse spleen tissue.Western blot assay was used to detect toll-like receptor 4(TLR4)/tumor necrosis factor receptor-associated factor 6(TRAF6)/nuclear factor kappa-B(NF-κB)pathway-related protein expression in lung tissue.Results Compared with the control group,damage of lung tissue was serious,the proliferation of bronchial epithelial goblet cells and the secretion of mucus increased,IgE concentration,TNF-α,IL-17 levels,Th17 cell proportion,Th17/Treg ratio,and TLR4,TRAF6,p-NF-κB p65 protein expression increased,while Treg cell proportion decreased in the BA group(P＜0.05).Compared with the BA group,the bronchial epithelial cupular cell proliferation and mucus secretion were reduced in the low-dose Zhike Pingchuan Formula group,the high-dose Zhike Pingchuan Formula group and the dexamethasone group,the lung tissue damage was improved,the concentration of IgE,levels of TNF-α,IL-17,the proportion of Th17 cells,the ratio of Th17/Treg and expression of protein levels of TLR4,TRAF6 and p-NF-κB p65 were reduced,and the proportion of Treg cell was elevated(P＜0.05).The trend of corresponding indexes in the LPS group was opposite to the above(P＜0.05).Compared with the high-dose Zhike Pingchuan Formula group,the pathological damage of lung tissue increased in the high-dose Zhike Pingchuan Formula+LPS group.The proliferation of bronchial epithelial goblet cells and the secretion of mucus increased,the IgE concentration,TNF-α,IL-17 levels,Th17 cell proportion,Th17/Treg ratio and TLR4,TRAF6,p-NF-κB p65 protein expression increased,while the Treg cell proportion decreased(P＜0.05).Conclusion Zhike Pingchuan Formula may reduce airway inflammation in BA mice by inhibiting TLR4/TRAF6/NF-κB pathway.

ObjectiveTo investigate the characteristics of serum perfluoroalkyl substances （PFASs） exposure and potential influencing factors among community residents in Songjiang District， Shanghai. MethodsIn August 2021， residents who underwent routine health checkups in a community in Songjiang District， Shanghai were recruited as study subjects. The inclusion criteria were adult residents who had lived in the area for more than 3 years， had no occupational exposure history， no underlying diseases， were not pregnant， and were able to complete the questionnaire independently and sign the informed consent form. A questionnaire survey was conducted and venous blood samples were collected. The concentrations of 15 PFASs in serum were determined using ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry （UPLC-MS/MS）. Ordered multi-class logistic regression， interquartile range （IQR）， and odds ratio （OR） were used to explore the influencing factors and risk magnitude of serum PFASs concentrations. ResultsOf the 15 PFASs， 14 were detected， and the detection rates of 7 PFASs were higher than 50%. The highest detected concentrations among the PFASs were PFOS （perfluorooctane sulfonate）， PFOA （perfluorooctanoic acid）， and PFHxS （perfluorohexane sulfonate）， with median concentrations of 48.61 μg∙L^-1， 37.29 μg∙L^-1， and 36.51 μg∙L^-1， respectively. The strongest correlation was between PFDA and PFUnDA （r=0.93， P<0.05）， followed by PFOS and PFDA （r=0.86， P<0.05）. Age， frequency of plastic product use， time spent indoors per day， personal annual income， tea consumption， and daily water intake were potential factors for exposure to PFASs. Among them， age was positively correlated with PFASs； tea consumption was positively correlated with PFNA and PFOA； PFHpA was negatively correlated with the frequency of plastic product use and personal annual income； and PFOS was negatively correlated with the time spent indoors per day. ConclusionThe exposure to serum PFASs among community residents in Songjiang District was relatively serious， and the main components were traditional PFOA， PFOS， and PFHx. Different sociodemographic characteristics had varying degrees of influence on the concentrations of PFASs in serum. The impact of PFASs exposure on the health of community residents deserves further investigation.