BACKGROUND:Troxerutin has been found to have a significant ameliorative effect on brain disorders,but there are fewer studies on the effects of troxerutin on the treatment of cerebral infarction and on neuronal cells. OBJECTIVE:To investigate the mechanism by which troxerutin regulates nuclear factor-κB signaling pathway to reduce brain injury and neuronal apoptosis in cerebral infarction rats. METHODS:Fifty clean grade rats were randomized into healthy group,model group,and troxerutin+nuclear factor-κB agonist group,troxerutin group,and nuclear factor-κB inhibitor group.Except for the healthy group,all other groups were used to establish a rat model of cerebral infarction by arterial ligation.The healthy and model groups were treated once a day with an equal amount of physiological saline by gavage.The troxerutin+nuclear factor-κB agonist group was intervened with 72 mg/kg troxerutin by gavage+20 mg/kg RANK intraperitoneally.The troxerutin group was treated with 72 mg/kg troxerutin by gavage.The nuclear factor κB inhibitor group was intervened intraperitoneally with 120 mg/kg nuclear factor κB inhibitor pyrrolidine disulfiram.Administration in each group was given once a day for 30 continuous days.Zea-longa was used to detect neurological damage in rats,hematoxylin-eosin staining was used to observe pathological changes,TUNEL was used to detect neuronal apoptosis,and immunoblotting and PCR were used to detect the expression of nuclear factor-κB p65 and nuclear factor-κB p50 at protein and mRNA levels,respectively. RESULTS AND CONCLUSION:Compared with the healthy group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65,nuclear factor-κB p50 mRNA and protein expression levels were elevated in the model group(P＜0.05).Compared with the model group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were decreased in the troxerutin+nuclear factor-κB agonist group(P＜0.05).Compared with the troxerutin+nuclear factor-κB agonist group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were reduced in the troxerutin group and nuclear factor-κB inhibitor group(P＜0.05).In addition,there was no difference between the troxerutin group and the nuclear factor-κB inhibitor group(P＞0.05).In the model group,there was a large number of cytoplasmic vacuolation,obvious edema and necrosis,and a large number of inflammatory cell infiltrations.In the troxerutin+nuclear factor-κB agonist,the swelling of brain tissue was reduced,and reticulate structures and condensed cells were reduced,still with some edema.In the troxerutin group and nuclear factor-κB inhibitor group,brain tissue swelling,neuronal edema degeneration,cytoplasmic vacuolation and neuronal nucleus consolidation were reduced,and the inflammatory cell infiltration was significantly decreased.To conclude,troxrutin can reduce the expression of neurological impairment,inhibit neuronal apoptosis and improve the pathological injury of brain tissue in rats with cerebral infarction,and its mechanism of action may be related to the modulation of nuclear factor-κB expression and related signaling pathways.

Objective:To analyze the risk factors for muscle cramps in maintenance hemodialysis patients and construct a nomogram prediction model.Methods:It was a retrospective cohort study. Patients undergoing regular hemodialysis at the Blood Purification Center of the Fourth Hospital of Hebei Medical University (West and East Campuses) from June 2023 to December 2023 were enrolled in this study. Patients were divided into a muscle cramps group and a non-muscle cramps group based on whether cramps occurred during or after dialysis. Patients from the West Campus were allocated to the training set, while those from the East Campus were assigned to the validation set, with an approximately 5∶1 ratio. Multivariate logistic regression analysis was used to identify risk factors for muscle cramps in the training set. A nomogram prediction model was constructed using R software. Model performance was evaluated using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis in both the training and validation sets.Results:A total of 498 maintenance hemodialysis patients were enrolled, including 409 in the training set (22.98% incidence of muscle cramps) and 89 in the validation set. Multivariate logistic regression analysis revealed that heart failure history ( OR=8.566, 95% CI 2.448-29.979, P=0.001), pre-dialysis corrected narrowed inferior vena cava width ( OR=0.531, 95% CI 0.433-0.650, P<0.001), increased ultrafiltration rate ( OR=1.002, 95% CI 1.001-1.003, P=0.002), decreased hemoglobin level ( OR=0.971, 95% CI 0.948-0.994, P=0.014), and decreased serum albumin ( OR=0.886, 95% CI 0.799-0.982, P=0.021) were independent associated factors for muscle cramps in the training set. The nomogram model based on these factors demonstrated an area under the ROC curve ( AUC) of 0.813 (95% CI 0.760-0.866, P<0.001) in the training set, with a Brier score of 0.129, indicating stable predictive performance. In the validation set, the area under of the ROC curve was 0.821 (95% CI 0.731-0.911, P<0.001) with a Brier score of 0.142. The decision curve showed that the model provided high clinical net benefit when the risk threshold probability for muscle cramps ranged from 0.22 to 0.77. Conclusion:Combined heart failure, narrowed inferior vena cava width, increased ultrafiltration rate, and decreased hemoglobin and serum albumin levels were the independent correlated factors for muscle spasm in maintenance hemodialysis patients. The nomogram model constructed based on these risk factors holds significant clinical value for predicting muscle cramps in maintenance hemodialysis patients.

Objective To explore the changes in serum pro-inflammatory cytokine factor and their relationship with memory function in patients with chronic insomnia comorbid and depression(ICD).Methods A total of 40 ICD patients and 41 chronic insomnia disorder(CID)patients were recruited at the Clinic of Sleep Disorder,and concurrently 41 healthy individuals as controls(CON)were recruited during the same period.The Pittsburgh sleep quality index(PSQI)and 17-item Hamilton depression rating scale(HAMD-17)were used to assess the severity of insomnia and depression in the subjects,and the nine box maze was used to evaluate their memory function.Enzyme linked immunosorbent assay was used to detect the levels of serum tumor necrosis factor(TNF)-α,TNF-β,interleukin(IL)-1β,IL-6,and serum amyloid A(SAA),and the correlation between pro-inflammatory cytokine factor levels and cognitive function was analyzed.Results The HAMD and PSQI scores were significantly higher in ICD and CID groups than in CON[HAMD:19.0(14.0,22.0)vs.10.0(7.5,12.5)vs.2.0(1.0,4.0);PSQI:17(15,19)vs.15(13,16)vs.2(0,3);P<0.01]which was also higher in ICD group than in CID group(P<0.01).The number of errors in spatial reference memory(SRM)and spatial working memory(SWM)were higher in the ICD and CID groups than in CON[SRM:2.5(1.0,4.0),vs.1.0(0,3.0)vs.0(0,1.0);SWM:5.00(4.00,7.75)vs.4.00(2.00,5.00)vs.1.00(1.00,2.50);P<0.01].The number of errors were also higher in SRM and SWM in ICD group than in CID group(P<0.01).The serum levels of TNF-α,TNF-β,IL-1β,IL-6,and SAA were higher in ICD and CID groups than in CON(P<0.01),and the serum levels of TNF-β and IL-6 were also higher in ICD group than in the CID group(P<0.01).In the ICD group,the partial correlation analysis showed that TNF-α(r=0.394,P=0.021)and IL-1β(r=0.398,P=0.020)were positively correlated with the number of SRW errors,while TNF-β(r=0.381,P=0.026)and SAA(r=0.446,P=0.008)were positively correlated with the number of SWM errors.TNF-β were also positively correlated with the number of recognition memory errors(r=0.347,P=0.044).Conclusion ICD patients have memory impairment,which may relate to increased levels of pro-inflammatory cytokine factor in their serum.

Objective:To analyze the risk factors for muscle cramps in maintenance hemodialysis patients and construct a nomogram prediction model.Methods:It was a retrospective cohort study. Patients undergoing regular hemodialysis at the Blood Purification Center of the Fourth Hospital of Hebei Medical University (West and East Campuses) from June 2023 to December 2023 were enrolled in this study. Patients were divided into a muscle cramps group and a non-muscle cramps group based on whether cramps occurred during or after dialysis. Patients from the West Campus were allocated to the training set, while those from the East Campus were assigned to the validation set, with an approximately 5∶1 ratio. Multivariate logistic regression analysis was used to identify risk factors for muscle cramps in the training set. A nomogram prediction model was constructed using R software. Model performance was evaluated using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis in both the training and validation sets.Results:A total of 498 maintenance hemodialysis patients were enrolled, including 409 in the training set (22.98% incidence of muscle cramps) and 89 in the validation set. Multivariate logistic regression analysis revealed that heart failure history ( OR=8.566, 95% CI 2.448-29.979, P=0.001), pre-dialysis corrected narrowed inferior vena cava width ( OR=0.531, 95% CI 0.433-0.650, P<0.001), increased ultrafiltration rate ( OR=1.002, 95% CI 1.001-1.003, P=0.002), decreased hemoglobin level ( OR=0.971, 95% CI 0.948-0.994, P=0.014), and decreased serum albumin ( OR=0.886, 95% CI 0.799-0.982, P=0.021) were independent associated factors for muscle cramps in the training set. The nomogram model based on these factors demonstrated an area under the ROC curve ( AUC) of 0.813 (95% CI 0.760-0.866, P<0.001) in the training set, with a Brier score of 0.129, indicating stable predictive performance. In the validation set, the area under of the ROC curve was 0.821 (95% CI 0.731-0.911, P<0.001) with a Brier score of 0.142. The decision curve showed that the model provided high clinical net benefit when the risk threshold probability for muscle cramps ranged from 0.22 to 0.77. Conclusion:Combined heart failure, narrowed inferior vena cava width, increased ultrafiltration rate, and decreased hemoglobin and serum albumin levels were the independent correlated factors for muscle spasm in maintenance hemodialysis patients. The nomogram model constructed based on these risk factors holds significant clinical value for predicting muscle cramps in maintenance hemodialysis patients.

Objective To explore the changes in serum pro-inflammatory cytokine factor and their relationship with memory function in patients with chronic insomnia comorbid and depression(ICD).Methods A total of 40 ICD patients and 41 chronic insomnia disorder(CID)patients were recruited at the Clinic of Sleep Disorder,and concurrently 41 healthy individuals as controls(CON)were recruited during the same period.The Pittsburgh sleep quality index(PSQI)and 17-item Hamilton depression rating scale(HAMD-17)were used to assess the severity of insomnia and depression in the subjects,and the nine box maze was used to evaluate their memory function.Enzyme linked immunosorbent assay was used to detect the levels of serum tumor necrosis factor(TNF)-α,TNF-β,interleukin(IL)-1β,IL-6,and serum amyloid A(SAA),and the correlation between pro-inflammatory cytokine factor levels and cognitive function was analyzed.Results The HAMD and PSQI scores were significantly higher in ICD and CID groups than in CON[HAMD:19.0(14.0,22.0)vs.10.0(7.5,12.5)vs.2.0(1.0,4.0);PSQI:17(15,19)vs.15(13,16)vs.2(0,3);P<0.01]which was also higher in ICD group than in CID group(P<0.01).The number of errors in spatial reference memory(SRM)and spatial working memory(SWM)were higher in the ICD and CID groups than in CON[SRM:2.5(1.0,4.0),vs.1.0(0,3.0)vs.0(0,1.0);SWM:5.00(4.00,7.75)vs.4.00(2.00,5.00)vs.1.00(1.00,2.50);P<0.01].The number of errors were also higher in SRM and SWM in ICD group than in CID group(P<0.01).The serum levels of TNF-α,TNF-β,IL-1β,IL-6,and SAA were higher in ICD and CID groups than in CON(P<0.01),and the serum levels of TNF-β and IL-6 were also higher in ICD group than in the CID group(P<0.01).In the ICD group,the partial correlation analysis showed that TNF-α(r=0.394,P=0.021)and IL-1β(r=0.398,P=0.020)were positively correlated with the number of SRW errors,while TNF-β(r=0.381,P=0.026)and SAA(r=0.446,P=0.008)were positively correlated with the number of SWM errors.TNF-β were also positively correlated with the number of recognition memory errors(r=0.347,P=0.044).Conclusion ICD patients have memory impairment,which may relate to increased levels of pro-inflammatory cytokine factor in their serum.

Objective To explore the effects of exposure to lipopolysaccharides in late pregnancy on age-related cognitive changes in offspring of mice,and to investigate whether there is a gender specific genetic effect.Methods Institute of cancer research(ICR)CD-1 mice during gestational days 15-17 were injected with lipopolysaccha-ride daily(LPS group,50 μg/kg),or equal volume of normal saline(CON group).At the age of 2 months after their delivery,LPS treated offspring mice(F1-LPS,male and female)were randomly selected and hybridized with age-matched wild-type CD-1 mice.F1-LPS males and females with different littermates,and F1-CON males and fe-males were hybridized to obtain F2 generations of different lineages.Similarly,F2-LPS mice were mated with wild-type mice to conceive the F3 generation.At the age of 3 and 18 months old,F1,F2,and F3 mice(n=8 in each group)were randomly selected to complete the Morris maze experiment in order to test their cognitive abilities.Re-sults Compared with 3-month-old CON mice,18-month-old CON mice showed poorer learning and memory abili-ties,especially in females.For Fl generation,the learning and memory abilities of the 3-month-old and 18-month-old F1-LPS mice were inferior to those of the same aged CON mice.For F2 generation,the 3-month-old F2-LPS-parental mice had poorer learning and memory compared to the same aged CON mice,while the F2-LPS-paternal mice only had poorer memory compared to the same aged CON group.The learning and memory abilities of 18-month-old F2-LPS paternal and F2-LPS-parental mice were inferior to those of the same aged CON mice.The learn-ing and memory abilities of F2-LPS maternal male mice were inferior to those of CON male mice,and the memory abilities of F2-LPS maternal mice were stronger than those of F2-LPS-parental mice.With regards to the F3 genera-tion,the memory of the 3-month-old F3-LPS-parental mice was poorer than that of the same aged CON mice.The learning and memory abilities of F3-LPS paternal and F3-LPS-parental mice at 18 months old were inferior to those of CON mice of the same age.The 18-month-old F3-LPS maternal and paternal male mice had better memory than F3-LPS-parental male mice.Conclusion Exposure to lipopolysaccharides in late pregnancy can accelerate age-re-lated cognitive decline in offspring mice,and it has a cross generational genetic effect and gender differences,mainly in paternal inheritance.

Objective:To investigate the clinical presentations and early recognition features of infant botulism(IB).Methods:Retrospective case analysis.The clinical data of 14 patients with IB admitted to the Department of Emergency of Beijing Children′s Hospital Affiliated to Capital Medical University between January 2019 and June 2023 were retrospectively analyzed.Results:The age of onset was 4.2(1.9-8.6) months.Ten cases(71.4%) were under 6 months, 9 of whom had a toxic trigger.The median time of first visit was 1(0-8) day.Thirteen cases(92.9%) complained of poor feeding/milk refusal, of whom pupillary light reflex was sluggish/absent in 12(85.7%) infants, 11(78.6%) had constipation, 10(71.4%) had weakness and/or lethargy, and 9(64.3%) had myasthenia of limbs and/or reduced movement of the extremities, decreased muscle tone and strength of the extremities occurred in all infants, and bowel sounds were diminished or vanished in 10 infants(71.4%).Only 2 infants were suspected of IB at the first visit.The mouse bioassay showed positive fecal specimens in all 14 infants, with a time of diagnosis of 3(1-10) days.Eleven cases(84.6%) had varying degrees of intestinal stasis, and 1 case had reduced physiologic pneumatosis in the small intestine.Ten infants underwent the neostigmine test: one was positive, and one was suspiciously positive.Ten cases(71.4%) required mechanical ventilation, 7(50.0%) of whom used invasive respiratory support.The median length of hospital stay was 26(11-61) days.All the infants were essentially cured by the time they left the hospital.Conclusions:If infants are previously fit and conscious but have an acute onset of illness with parental complaints of poor appetite, weak reactions, and weakness of the extremities and are found to have cranial nerve palsy, signs of acute flaccid paralysis, abdominal distension, and diminished bowel sounds during the examination, the possibility of IB should be considered, and a fecal specimen should be sent for botulinum toxin assay as soon as possible.

Objective:To summarize the clinical characteristics of children with severe pneumonia requiring mechanical ventilation due to human Boca virus infection.Methods:Clinical data of children with severe human Boca virus pneumonia required mechanical ventilation who were admitted to the emergency intensive care unit at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to June 2023 were retrospectively analyzed.Results:A total of ten children with human Boca virus pneumonia required mechanical ventilation were included,including seven males with a median age of 21.5(10.0-42.0) months and six children less than two years old.Six patients were admitted to hospital in the fall of 2022 and four were in the summer of 2023.All cases had cough,wheezing and fever.The wheezes could be heard in all patients admitted to hospital for physical examination.Respiratory sounds were reduced in six cases,and moist crackles were heard in two cases.Two patients had thrush.One patient with bronchial lavage culture showed streptococcus pneumoniae and staphylococcus aureus.One patient had human herpesvirus type 6 infection on day 5 of the course of disease,and one child had rhinovirus.There was no evidence of co-infection in the remaining five cases.All patients were given mechanical ventilation for respiratory failure,and the median mechanical ventilation time was 85 (46-165) hours.Each patient was examined by bronchoscope for 1-3 times.Bronchoscopy manifested endobronchial inflammation,mucosal swelling,increased secretions (10/10),mucous thrombus formation (8/10) and scattered necrotic epithelium (4/10).All patients were discharged after improvement and the median length of administration was 9 (6-14) days.Conclusion:Human Boca virus is one of the important pathogens of severe pneumonia in children,with severe cough,wheezing and feve,which can lead to endobronchial trachea inflammation,easy to form mucous embolus and mucosal necrosis.In severe cases,mechanical ventilation and bronchoscopy are required,and most of them have good prognosis.

ObjectiveTo investigate the impact of yang deficiency syndrome on the progression to end-point events of diabetic kidney disease （DKD）. MethodsA retrospective study among patients with stage Ⅳ DKD admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine from September 1st， 2016 to September 30th， 2021 was conducted. Data on the patients' general information， clinical indicators including duration of diabetes， duration of proteinuria， history of smoking and drinking， hemoglobin （HGB）， fasting blood glucose （FBG）， albumin （ALB）， serum creatinine （Scr）， urea nitrogen （BUN）， uric acid （UA）， cholesterol （TC） ， triglycerides （TG）， low-density lipoprotein （LDL）， 24-hour urine protein quantification （24h-UTP） and estimated glomerular filtration rate （eGFR）， and TCM syndromes including symptoms， tongue and pulse， and syndrome scores were collected. The patients were divided into exposure group （yang-deficiency group） and non-exposure group （non-yang-deficiency group）. The general information， clinical indicators and incidence rates of end-point events were compared， and the impact of yang deficiency syndrome on the end-point events of stage Ⅳ DKD was analyzed. Survival analysis was performed using Kaplan-Meier method， and multivariate Cox proportional risk models were used to identify independent predictors of end-point events. ResultsA total of 160 patients with stage Ⅳ DKD were included in the study， including 43 cases of yang deficiency syndrome and 117 cases of non-yang deficiency syndrome. Compared to those in the non-yang deficiency group， the waist circumference， BUN and the incidence of end-point events in the yang deficiency group were significantly higher （P＜0.05 or P＜0.01）. Spearman correlation analysis showed that yang deficiency syndrome was positively correlated with incidence of end-point events of stage Ⅳ DKD （r = 0.167， P = 0.035）. Furthermore， 24h-UTP and BUN levels were also positively correlated with end-point events in stage Ⅳ DKD patients （P＜0.01）， while ALB and HGB levels were negatively correlated （P＜0.01）. Kaplan-Meier survival curves showed that yang deficiency syndrome was associated with an increased risk of end-point events （Log Rank P = 0.011）. Moreover， 24h-UTP levels ≥3500 mg， BUN level ≥8 mmol/L， ALB level ＜30 g and HGB level ＜11 g were all associated with the increase of the risk of end-point events （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that yang deficiency syndrome was an independent risk factor for patients with stage Ⅳ DKD to progress into end-point events （HR = 2.36， 1.32 to 4.21； P = 0.004）， as well as 24h-UTP ≥ 3500 mg， BUN ≥ 8 mmol/L， HGB＜11 g and ALB＜30 g （P＜0.05 or P＜0.01）. ConclusionsFor stage Ⅳ DKD， patients with yang deficiency syndrome are more likely to have end-point events， which is an independent risk factor for the progression into end-point events.

Objective:To evaluate the effect of different clear fluid fasting duration on the fluid responsiveness after anesthesia induction in pediatric patients with congenital heart disease.Methods:One hundred pediatric patients with congenital heart disease who underwent elective atrial septal defect or ventricular septal defect correction surgery at Shanghai Children′s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine from December 2023 to February 2024 were selected. They were of either sex, aged 6 months to 3 yr, with a body mass index of 13-19 kg/m 2, and classified as American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ. Patients who adhered to the prescribed preoperative clear fluid fasting regimen, with a fasting duration of 6 h or longer before surgery, were included in the long fasting (LF) group, while those who were prescribed multi-dimensional nutritional solution until 2 h before surgery with a solid fasting duration≥6 h were considered for inclusion in the short fasting (SF) group. The diastolic blood pressure (DBP) was recorded immediately before and after liver compression test at pre-induction of anesthesia and immediately before and after liver compression test at post-induction of anesthesia, and the changes in DBP before and after the liver compression test (ΔDBP) were calculated. Positive fluid responsiveness was defined as an increase in ΔDBP ≥ 6.25%. The positive rate of fluid responsiveness before and after anesthesia induction was calculated. Results:Sixty-four patients were finally included, and both LF and SF groups included 32 cases. Before the induction of anesthesia, the positive rate of fluid responsiveness induced by liver compression was 28.1% in LF group and 18.8% in SF group, and the difference was not statistically significant ( P>0.05). However, after the induction of anesthesia, the positive rate of fluid responsiveness induced by liver compression was 56.3% in LF group and 28.0% in SF group, with a statistically significant difference observed ( P<0.05). Compared with the baseline before anesthesia induction, the positive rate of fluid responsiveness was significantly increased in LF group( P<0.05), and no significant change was found in the positive rate of fluid responsiveness in SF group ( P>0.05). Conclusions:The prolonged clear fluid fasting may lead to an increase in the positive rate of fluid responsiveness following anesthesia induction in pediatric patients with congenital heart disease, presenting as a state of hypovolemia.