BACKGROUND:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells.The Toll-like receptors(TLRs)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway plays an important role in the development of the disease.Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE:To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models,which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway. METHODS:The literature related to the topic from January 2002 to December 2022 was searched in CNKI,WanFang and PubMed databases.A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION:The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response.The TLRs/MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells,destroying the integrity of the blood-brain barrier,and promoting the activation of T cells,B cells and microglia.By targeting TLRs,MyD88 and NF-κB molecules,inhibiting the activation or signal transduction of TLRs,MyD88 and NF-κB,and reducing the secretion of pro-inflammatory factors,multiple sclerosis can be treated.Animal studies have shown that active ingredients of traditional Chinese medicines,such as flavonoids and glycosides,and traditional Chinese medicine compound formulas,such as Buyang Huanwu Tang,can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway,which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis.

OBJECTIVE To analyze the influential factors for rivaroxaban-induced bleeding events in patients with non- valvular atrial fibrillation （NVAF） and coronary heart disease. METHODS A total of 64 hospitalized patients with NVAF complicated with coronary heart disease who were treated with rivaroxaban and admitted to the Fuzhou University Affiliated Provincial Hospital from November 2021 to May 2023 were included in this retrospective study. The demographic data， laboratory test indexes and other general clinical data， and steady-state trough concentration of rivaroxaban were collected， and the dose- adjusted trough concentration was calculated. The occurrence of bleeding events within 6 months after discharge was recorded. The univariate analysis and binary Logistic regression analysis were adopted to determine the independent risk factors of rivaroxaban- related bleeding events. The binary Logistic regression equation was constructed to predict the probability of bleeding events. The area under the receiver operator characteristic （ROC） curve （AUC） was used to analyze the predictive value of the regression equation. RESULTS Among 64 patients， 19 patients had 24 case-times bleeding events， most of which were mild bleeding （19 case-times， 79.2%）， and mainly gastrointestinal bleeding （17 case-times， 70.8%）. After symptomatic treatment and adjustment of the anticoagulant regimen， most of them were improved or cured. In the univariate analysis， the proportion of patients with a history of anemia， platelet count， urea nitrogen content， steady-state trough concentration of rivaroxaban， dose-adjusted trough concentration and coagulation indexes [international normalized ratio， prothrombin time （PT）， activated partial thromboplastin time] in bleeding group were significantly more or higher than those in non-bleeding group， while the albumin level was significantly lower than that in non-bleeding group （P＜0.05）. In binary Logistics regression analysis， high PT level （odds ratio＝1.473， 95% confidence interval＝1.103-1.967， P＝ 0.009） and high rivaroxaban dose-adjusted trough concentration （odds ratio＝1.174， 95% confidence interval＝1.018-1.355， P＝ 0.027） were independent risk factors for rivaroxaban-related bleeding events. The binary Logistic regression equation of bleeding event prediction probability （P） was LogitP＝－6.975+0.387×PT level+0.161×dose-adjusted trough concentration， and the AUC of the ROC curve was 0.825 （95% confidence interval was 0.708-0.909， P＜0.001）. CONCLUSIONS The risk factors of rivaroxaban-related bleeding events in patients with NVAF and coronary heart disease include previous anemia history， high platelet count， high urea nitrogen content， high rivaroxaban steady-state trough concentration， high dose-adjusted trough concentration， high coagulation indexes and low albumin level. High PT level and high dose-adjusted trough concentration are independent risk factors that can be used to predict the risk of rivaroxaban-induced bleeding events. The regression equation has good predictive value.

Objective To analyze the risk factors of venous thromboembolism(VTE)after endoscopic surgery in elderly patients with urinary system calculi,construct a prediction model and validate it.Methods A retrospective analysis was conducted on the clinical data of 402 elderly patients(≥ 60 years)with urinary system calculi who underwent endoscopic surgery in our hospital during Jan.2018 and Jan.2023.The patients were divided into VTE group(n=43)and non-VTE group(n=359)based on whether VTE occurred after surgery.Risk factors of VTE were screened with univariate and multivariate logistic regression analyses.Based on the screening results(P＜0.05 for the factor),a nomogram prediction model was established,the receiver operating characteristic(ROC)curve was drawn,the area under the curve(AUC)was calculated to determine the efficacy of the model,and a calibration chart was drawn to determine the accuracy of the model.Results Univariate analysis showed that age＞70 years,body mass index(BMI)≥30,VTE history,history of malignant tumors,diabetes,operation time＞180 min,diuretic use during operation,and postoperative ambulation time＞24 h were risk factors of VTE(P＜0.05).Logistic regression analysis showed that age＞70 years,BMI ≥ 30,history of VTE,history of malignant tumors,and operation time＞180 min were independent risk factors of VTE(P＜0.05).The AUC in the ROC curve of the validation set data was 0.789(95％CI:0.731-0.848,P＜0.001).The calibration chart showed that the calibration curve was close to the standard curve(Brier=0.13).Conclusion Age＞70 years,BMI ≥30,history of VTE,history of malignant tumors,and surgery time＞180 min are independent risk factors of postoperative VTE in elderly patients with urinary system calculi undergoing endoscopic surgery.The prediction model can effectively predict the risk factors of postoperative VTE.

Objective To explore the efficacy of noninvasive cardiac output monitoring(NICOM)combined with intensive care ultrasound in volume management of patients with hemodynamic disorders after cardiac surgery.Methods Ninety-one patients with hemodynamic disorders after cardiac surgery admitted to Zhejiang Provincial People's Hospital from January to October 2021 were selected as study objects,and were divided into control group(n=46)and observation group(n=45)according to random number method.The control group underwent traditional hemodynamic monitoring to guide fluid management.In observation group,the volume management strategy based on NICOM combined with intensive care ultrasound guided fluid management.The duration of tracheal intubation removal,left ventricular ejection fraction(LVEF),brain natriuretic peptide(BNP),postoperative lactic acid normalcy time,diuretic use rate,postoperative urine volume,incidence of acute heart failure,intra-aortic balloon pump retention rate,mechanical ventilation duration and intensive care unit(ICU)stay were compared between two groups.Results The proportion of patients with successful extubation in observation group was significantly higher than that in control group(χ2=14.773,P=0.001).At discharge,LVEF in both groups was significantly higher than that at admission,BNP was significantly lower than that at admission(P<0.05).LVEF in observation group was significantly higher than that in control group,and BNP was significantly lower than that in control group(P<0.05).The time of lactic acid normalization,mechanical ventilation duration and ICU stay in observation group were significantly shorter than those in control group,diuretic use rate,cumulative fluid balance volume and incidence of acute heart failure were significantly lower than those in control group,and the postoperative urine volume was significantly higher than that in control group(P<0.05).Conclusion The volume management strategy based on NICOM combined with intensive care ultrasound can significantly reduce the amount of fluid replenishing in patients with hemodynamic disorders after cardiac surgery,improve cardiac function and shorten the time of mechanical ventilation,which is worthy of clinical promotion and application.

Objective:To document the impact of information-based, stepwise, intensive rehabilitation therapy on patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:Eighty such patients in an intensive care unit (ICU) were randomly divided into a control group and an observation group, each of 40. The control group received routine ICU rehabilitation, while the observation group underwent information-based, step-wise ICU rehabilitation. Upon admission to and discharge from the ICU, the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, and diaphragm functioning were compared between the two groups. The duration of mechanical ventilation, the incidence of ventilator-associated pneumonia (VAP), length of stay in the ICU, incidence of delirium, and the incidence of deep vein thrombosis (DVT) were also recorded. The number of patients readmitted to the ICU after discharge, and the 28-day hospital mortality rate were recorded as well.Results:Significant improvement was observed in both groups in terms of their lung and diaphragm functioning, as well as in the rehabilitation- and hospital-related indicators. At discharge, significantly greater improvements were observed in the observation group compared with the control group in terms of their average FEV1, FVC, FEV1/FVC, inspiratory and expiratory diaphragm thickness, and diaphragm thickening rate. The average duration of mechanical ventilation and of rehabilitation interruptions was significantly less in the observation group. And incidents of accidental extubation, VAP, delirium and DVT were significantly fewer in the observation group as well. Their ICU stays tended to be significantly shorter without any significant difference between the two groups in the 28-day hospital mortality rate. The control group spent significantly less time in their daily rehabilitation sessions, with the result that significantly fewer of them achieved a grading of 2 or better on the mMRC respiratory questionnaire.Conclusion:Information-based stepwise intensive rehabilitation treatment can effectively improve the pulmonary and diaphragmatic function of AECOPD patients admitted to an ICU, shorten their mechanical ventilation time and the length of their ICU stay, and lower their incidence of VAP and DVT during hospitalization.

Objective To explore the effect of oxycodone hydrochloride on inflammation and neuro-nal apoptosis in epileptic rats through c-Jun amino terminal kinase(JNK)/p38 mitogen activated protein kinase(p38 MAPK)signaling pathway.Methods After epileptic rat model was success-fully constructed,72 epileptic rats were randomly divided into model group,low-,medium-and high-dose oxycodone hydrochloride groups(0.125,0.25 and 0.5 mg/kg),anisomycin(JNK activa-tor 5 mg/kg)and combined group(0.5 mg/kg oxycodone hydrochloride+5 mg/kg anisomycin),with 12 rats in each group.Another 12 healthy rats were selected as control group.In 24 h after the end of administration,the frequency and duration of seizures were recorded for all rats.ELISA was used to detect the serum levels of TNF-α and IL-6,HE staining was employed to observe the his-topathological changes in hippocampal CA1 region,and TUNEL staining was applied to detect the apoptosis of CA1 region neurons.The expression of JNK,p-JNK,p38 MAPK,p-p38 MAPK and Caspase-3 in hippocampal CA1 region was detected by Western blotting.Results Compared with the rats from the control group,those of the model group showed higher frequency and longer du-ration of seizures,higher serum TNF-α and IL-6 levels,increased apoptotic rate of hippocampal CA1 neurons,and elevated p-JNK/JNK ratio,p-p38 MAPK/p38 MAPK ratio and Caspase-3 expression(P＜0.05).While low-,medium-and high-dose oxycodone hydrochloride treatment re-versed above changes in frequency and duration of seizures,serum TNF-α and IL-6 levels,neuro-nal apoptosis,p-JNK/JNK ratio,p-p38 MAPK/p38 MAPK ratio and Caspase-3 expression(P＜0.05).In the anisomycin group,higher frequency and longer duration of seizures,elevated serum TNF-α and IL-6 levels,increased neuronal apoptotic rate in hippocampal CA1 region,and en-hanced p-JNK/JNK ratio,p-p38 MAPK/p38 MAPK ratio and Caspase-3 expression(P＜0.05).Lower frequency and shorter duration of seizures,decreased serum TNF-α and IL-6 levels,and re-duced neuronal apoptotic rate in hippocampal CA1 region were observed in the combined group than the anisomycin group(P＜0.05).The combined group obtained statistically lower p-JNK/JNK ratio,p-p38 MAPK/p38 MAPK ratio and Caspase-3 expression in hippocampal CA1 region than the high-dose group,and opposite results than the anisomycin group(0.89±0.12 vs 0.25± 0.05 vs 1.08±0.16,0.81±0.08 vs 0.21±0.04 vs 0.94±0.12,0.79±0.12 vs 0.26±0.04 vs 0.89± 0.14,P＜0.05).Conclusion Oxycodone hydrochloride can reduce inflammatory response,im-prove epileptic symptoms and pathological damages,and protect neurons in epileptic rats,which is related to the inhibition of JNK/p38 MAPK signaling pathway.

Objective To analyze the prevalence of hypertension in coal mine male workers and its influencing factors. Methods A total of 1 772 coal mine male workers from a coal mining group were selected as research subjects using multi stage complex sampling method. The prevalence of hypertension and its influencing factors were analyzed. Results The prevalence of hypertension was 33.0%（585/1 772）. Logistic regression analysis of complex sampling showed that body mass index， family history of hypertension， alcohol-drinking， tea-drinking， and snoring were independent risk factors for hypertension（all P<0.05），after adjusting for the effects of other inclusion factors on the basis of age. The risk of hypertension in coal mine male workers was higher in those with overweight and obesity than in normal weight（all P<0.01），higher in those with family history of hypertension than in no history of hypertension（P<0.01），and higher in tea drinkers than in no tea drinkers （P<0.05）. The more the alcohol consumption and the higher the frequency of snoring，the higher the risk of hypertension（all P<0.01）. These factors have a dose-response relationship. Conclusion The body mass index，family history of hypertension，alcohol-drinking，tea-drinking and snoring can affect the prevalence of hypertension in coal mine male workers.

ObjectiveTo investigate the preventive effect and mechanism of Aurantii Fructus Immaturus and naringin on postoperative intestinal adhesion in rats. MethodThe preventive effect of Aurantii Fructus Immaturus and naringin on intestinal adhesion was studied by cecal scraping model of rats， the model rats were randomly divided into model group， dexamethasone sodium phosphate group and Aurantii Fructus Immaturus low， medium and high dose groups （1.58， 3.15， 6.30 g·kg^-1·d^-1）， tsham-operated group was treated with an incision in the abdomen. Adhesion was assessed by Nair method after 7 d of administration. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology and inflammatory cell infiltration of cecum， the expression of matrix metalloproteinase-9 （MMP-9） in cecal adhesion was detected by immunohistochemistry. Meanwhile， intestinal adhesion model rats were randomly divided into model group， dexamethasone sodium phosphate group， naringin low， medium， high dose groups （50， 100， 200 mg·kg^-1·d^-1）， and the sham-operated group was treated with an incision in the abdomen. Adhesion was assessed after 7 d of administration， HE staining was used to observe the pathological morphology and inflammatory cell infiltration in the cecum， and the expression of MMP-9 in the cecal adhesion tissue was detected by immunohistochemistry. Expressions of transforming growth factor-β₁ （TGF-β₁） and α-smooth muscle actin （α-SMA） in cecum were analyzed by western blot. ResultAurantii Fructus Immaturus could inhibit the formation of postoperative intestinal adhesions in rats， reduce the inflammatory response of damaged cecum tissue， and up-regulate the expression of MMP-9 in the adherent tissue in a dose-dependent manner. All dose groups of naringin could significantly inhibit the formation of postoperative intestinal adhesions in rats， reduce inflammatory cell infiltration and fibrous proliferation in tissue， up-regulate the expression of MMP-9 in the adherent tissue in a dose-dependent manner， and inhibit the expression of TGF-β₁ and α-SMA in cecal tissue. ConclusionAurantii Fructus Immaturus and naringin can reduce postoperative intestinal adhesion formation in rat model， and their effects may be related to reducing tissue fibrosis and accelerating extracellular matrix degradation.

Objective:To investigate the etiological diagnostic value of metagenomic sequencing in central nervous system (CNS) infectious diseases.Methods:A total of 170 patients with central nervous system infection admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2020 were selected as the study subjects according to inclusion and exclusion criteria. General clinical data and pathogen test results were collected. All included patients underwent routine examination and mNGS test, and were divided into the conventional method test group and mNGS test group according to the test results. The measurement data conforming to normal distribution were represented by ± s; The measurement data that did not conform to normal distribution were represented by median and interquartile range. The classification data were expressed by the number of cases and percentage( n,%), and were compared by χ2 test or Fisher's exact test. Consistency test was represented by Kappa value. The detection of pathogenic microorganisms by the two methods and the rule of pathogen spectrum were compared and analyzed. Results:The overall positive rate of mNGS in CNS infectious diseases was higher than that of conventional methods (58.23% vs. 18.82%), and the difference was statistically significant ( P<0.01). Among the 20 samples which were both positive by the two methods, 10 cases were completely pathogenic, 5 cases were partially consistent and 5 cases were completely inconsistent. In the detection of tuberculous nervous system infection, the positive rates were 66.7%, 53.8%, 44.0%, 40.0%, 4.0% in blood T-SPOT, cerebrospinal fluid mNGS, ADA, Mycobacterium tuberculosis DNA and tuberculous specific antibody, respectively. The positive rate of acid-fast staining was 0. The positive rate of mNGS combined with conventional method was 80.8%. Conclusions:The detection rate of mNGS in CNS infection is better than that of conventional methods. However, it does not show obvious superiority in the detection rate of Mycobacterium tuberculosis associated nervous system infection. In general, mNGS detection of pathogenic bacteria is more extensive, which is conducive to a thorough and comprehensive understanding of the bacterial characteristics of central nervous system infection. The combination of the two methods can make up for the deficiency of clinical routine detection to a certain extent, and can maximize the detection rate.

Objective:To explore the distribution characteristics of respiratory pathogens in patients with community-acquired pneumonia in Lianyungang.Methods:A total of 612 patients admitted to the second people′s Hospital of Lianyungang City because of community-acquired pneumonia (CAP) in 2019 were selected as subjects. Sputum or pharyngeal swabs were collected to extract nucleic acids, and 13-fold nucleic acids of respiratory pathogens were detected by PCR capillary electrophoresis fragment analysis. SPSS statistical software and GraphPad5.0 statistical mapping software were used for statistical analysis.Results:The physical examination rate of respiratory pathogens in the adult group was 82.0% in winter, 48.4% in spring, 28.0% in autumn, 20.0% in summer, χ 2=38.473, P=0.000. The positive rate of nucleic acid detection was significantly different in different seasons, among which the physical examination rate of respiratory pathogens in winter was the highest. The physical examination rate of respiratory pathogens in the juvenile group was 86.0% in spring, 76.2% in winter, 71.3% in summer and 66.7% in autumn, χ 2=7.946, P=0.047 . The positive rate of nucleic acid detection was calculated according to gender grouping. The comparison of nucleic acid positive rate between adult group and juvenile group in different seasons: 86.0% vs 48.4% in spring, χ 2=19.436, P=0.000; 71.3% vs 20.0% in summer, χ 2=22.180, P=0.000; 66.7% vs 28.0% in autumn, χ 2=13.485, P=0.000; 76.2% vs 82.0% in winter, χ 2=0.758, P=0.384. Except in winter, the detection rate of nucleic acid of pathogens in the juvenile group was significantly higher than that in the adult group. Conclusions:The nucleic acid detection rate and etiological distribution characteristics of respiratory pathogens are different in patients with community-acquired pneumonia in different seasons and different age groups. 13 kinds of multiple detection methods of respiratory pathogens can provide favorable laboratory data support for the diagnosis and treatment of clinical CAP patients.