ObjectiveTo screen key genes associated with neuroblastoma （NB） diagnosis and prognosis using the Gene Expression Omnibus （GEO） database， and to investigate the expression and clinical significance of nucleoporin 93 （NUP93） in NB tissues. MethodsNB gene chip data （GSE73517， GSE49710， GSE19274） were retrieved from the GEO database. Differentially expressed genes （DEGs） commonly upregulated in high-risk groups were screened. The R2 database was then used to assess the prognostic value of DEGs that were commonly upregulated in the MYCN amplification group. Finally， NUP93 expression levels in the tissues from 60 NB， 25 ganglioneuroblastoma （GNB）， and 26 ganglioneuroma （GN） cases were measured by immunohistochemistry . ResultsTwenty-five DEGs were identified as commonly upregulated in high-risk groups. Among these， 10 genes （SIVA1， NUP93， STIP1， LSM4， RAI14， MYOZ3， KNTC1， TNFRSF10B， TACC3 and CEP152） showed significantly higher expression in MYCN-amplified subgroups （P＜0.05）. Survival analysis revealed that high NUP93 expression was associated with shorter overall survival （HR = 4.0， 95% CI： 3.0，5.3， P = 1.80 × 10⁻³⁴）. Immunohistochemistry results revealed that NUP93 expression in NB tissues was significantly higher than in GNB and GN tissues （P＜0.001）. NUP93 expression was positively correlated with high mitosis-karyorrhexis index （MKI； P=0.040）， poor differentiation （P＜0.001）， and MYCN expression （r_s = 0.793， P ＜0.001）. ConclusionsHigh expression of NUP93 is associated with high MKI and poor differentiation， and predicts unfavorable prognosis in patients with NB， suggesting it may promote tumor progression by regulating MYCN. NUP93 has the potential to be a novel diagnostic biomarker and therapeutic target for NB.

Objective To establish evaluation of ozagrel sodium by weighted TOPSIS method so as to provide a reference for improving the rational use of ozagrel sodium.Methods Based on the drug instructions,guidelines,relevant literatures and Delphi method,the evaluation criteria for the clinical rationality of ozagrel sodium were formulated.Attribute hierarchical model(AHM)was used to assign weights to the indicators,the weighted TOPSIS method was employed to analyze and evaluate the rationality of 108 patients that discharged from the Third People's Hospital of Henan Province from January 2021 to April 2022.Results The reponse rates of two rounds of expert advice questionnaires were 100％,the authoritative coefficients(Cr)were 0.85,0.83(＞0.70),and the experts fully affirmed the items of the standard.Among the 108 cases evaluated,37 cases(34.26％)were judged to be reasonable,52 cases(48.15％)were judged to be basically reasonable and 19 cases(17.59％)were judged to be unreasonable.The main unreasonable problems were manifested in indications,the timing of administration,drug course and monitoring of efficacy and laboratory parameters.Conclusion The method of DUE of ozagrel sodium based on weighted TOPSIS is more comprehensively and intuitively.The application of ozagrel sodium in the hospital is relatively standardized,but there are problems in the course of medication,indications,and timing of administration.So it is necessary to promote the rational use by strengthening the cooperation between pharmacists and physicians,and improving pharmaceutical intervention.

Objective To establish the drug use evaluation(DUE)criteria of recombinant human prourokinase(rhPro-UK),and to provide reference for the rational clinical application of rhPro-UK.Methods Based on the drug instructions of rhPro-UK,DUE standard rules were established by referring to relevant guidelines,expert consensus,authoritative literature and expert consultation.The medical records of hospitalized patients treated with rhPro-UK from January 2019 to May 2022 in Xilin Gol League Central Hospital were evaluated by retrospective investigation.The effectiveness of rhPro-UK was evaluated based on clinical outcome,and its safety was evaluated based on the incidence and severity of adverse reactions.Results A total of 230 cases were included,and 4 cases fully met the evaluation criteria(medication indication,medication process,medication results),accounting for 1.74％.There were 226 patients(98.26％)with irrational drug use,mainly manifested in two aspects of drug indication and drug process(administration mode and dosage).Treatment was effective in 221 patients,with an overall effective rate of 96.09％;139 patients experienced adverse reactions,with an incidence rate of 60.43％.Conclusion The clinical use of rhPro-UK in our hospital is irrational in the indication of medication and the process of medication,and the establishment of the DUE standard rules of rhPro-UK can provide a reference to standardize the clinical application of rhPro-UK and promote its rational use.

Objective To establish the drug use evaluation(DUE)standard of somatostatin and evaluate the rationality of its clinical use,so as to provide a reference for the rationally clinical application of somatostatin.Methods Based on the specification of somatostatin for injection,related guidelines and literature,DUE standard was established.Evaluate the rationality and standardization of the use of somatostatin for injection at Beihai People's Hospital from January 2021 to December 2021 based on the established DUE standards.Results A total of 407 patients were included,with a medication reasonable rate of 94.84％.The irrational use of drug included unreasonable indications(13 cases,3.19％),unreasonable drug use frequency(7 cases,1.72％),and unreasonable drug interactions(1 case,0.25％).Conclusion The somatostatin for injection DUE standard established is feasible and practical.The clinical application of somatostatin for injection in this hospital is basically reasonable,but there are still some irrational use of somatostatin,which should be strengthened for intervention.

Objective To establish the drug use evaluation(DUE)criteria for bemiparin sodium injection,and evaluate the use of bemiparin sodium injection by weight technique for order prefer by similarity to ideal solution(TOPSIS),and to provide reference for improving the rational use of bemiparin sodium injection.Methods Based on the instructions of bemiparin sodium injection,and referring to relevant guidelines and literatures,the DUE criteria of bemiparin sodium injection was established by expert consultation.The weighted TOPSIS method was used to evaluate the rationality medication in the cases of inpatients who use bemiparin sodium injection from June to July 2021 in the Tongji Hospital of Tongji University.Results In the established DUE criteria of bemiparin sodium injection,the top two relative weight coefficients of ten secondary indicators were contraindications and adverse reaction disposal,and the bottom two were administration methods and indications.A total of 100 medical records were including.There was not a case close to the optimal regimen(Ci≥0.8)(reasonable);Ci was between 0.6 and 0.8(basically reasonable)in 83 cases(83.00％);and Ci＜0.6(unreasonable)in 17 cases(17.00％).The unreasonable uses of bemiparin sodium injection mainly appeared in off-lable uses of indications and the dosing method,a potential drug-drug interaction,inappropriate dosage,and violation of drug contraindications.Conclusion The drug use evaluation method of bemiparin sodium injection based on weighted TOPSIS method can synthesize multiple evaluation indexes,and the evaluation results are objective and reliable.The results showed that most clinical application of bemiparin sodium injection in this hospital was basically reasonable,but to provide basis for rational clinical drug use and to ensure patients'medication safety,it is necessary to accelerate the off-label evidence-based evaluation process and strengthen the management of rational drug use.

Objective To establish a drug use evaluation(DUE)criteria for alteplase in the treatment of acute ischemic stroke(AIS),and to evaluate the use of the drug by weighted TOPSIS method,to provide a reference for rational use of alteplase.Methods Based on the drug package insert,relevant guidelines,the DUE criteria for alteplase in the treatment of AIS were developed combined with expert consultation.The weighted TOPSIS method was used to evaluate the rationality of alteplase use in inpatients with AIS in the People's Hospital of Guangxi Zhuang Autonomous Region from January 2020 to June 2022,based on the attribute hierarchy model.Results A total of 126 medical records were included.Among them,80 cases(63.49％)exhibited a high degree of adherence(C,＞0.8)between the prescribed drug regimens and the optimal recommendations,which was considered reasonable.Additionally,40 cases(31.75％)fell within the range of 0.6 ≤ Ci ≤ 0.8,indicating a basic reasonable adherence,and 6 cases(4.76％)had a C,＜0.6,suggesting an unreasonable level of adherence.The irrational use of the drug mainly involved contraindications(32.54％),dosage(7.14％),and drug conversion(7.14％),among other aspects.Conclusion The weighted TOPSIS method is used to evaluate the rationality of alteplase in the treatment of acute ischemic stroke(AIS),and the results are intuitive and comprehensive.There are still problems in the use of alteplase in this hospital,and it is necessary to strengthen intervention to promote rational clinical use of alteplase in terms of contraindication of medication and dosage,etc.

Gut microbiota is involved in maintaining intestinal homeostasis. The bidirectional communication between intestinal flora and brain can also be conducted through the neuro-immune-endocrine network, namely, the "microbiota-gut-brain axis". A number of studies have shown that the "microbiota-gut-brain axis" disorder plays an important role in the occurrence, development and prognosis of some cerebrovascular diseases, such as cerebral small vessel disease and stroke. This article introduces the latest research progress of the relationship between gut microbiota and cerebrovascular diseases, so as to provide more ideas and options for the treatment of cerebrovascular diseases.

Objective:To observe the effect of early goal directed sedation (EGDS) on cerebral oxygen metabolism in patients with acute brain injury.Methods:A prospective cohort study was conducted. A total of 108 patients with acute brain injury admitted to the intensive care unit (ICU) of the Third Medical Center of the PLA General Hospital from January 2015 to December 2019 were enrolled. According to the patient's condition, dexmedetomidine contraindication and tolerance, and combined with the wishes of patients' families, they were divided into EGDS group and on-demand sedation group. Routine treatments such as surgery, mechanical ventilation, dehydration and reduction of intracranial pressure with mannitol, hemostasis or antiplatelets therapy were given according to the patient's condition. All patients were continuously given sufentanil by intravenous infusion for analgesia. Patients in the EGDS group were sedated by continuously intravenous infusion of dexmedetomidine (0.2-0.7 μg·kg -1·min -1) for 72 consecutive hours. Patients in the on-demand sedation group received intravenous bolus of propofol (0.5-1.0 mg/kg) when treatments were interfered due to agitation. Hemodynamic indexes [heart rate (HR), mean arterial pressure (MAP), cerebral perfusion pressure (CPP), intracranial pressure (ICP)], sedation indexes [bispectral index (BIS)], severity indexes [acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, Glasgow coma score (GCS)] and cerebral oxygen metabolism indexes [jugular venous blood lactate (Lac), jugular venous oxygen saturation (SjvO 2), cerebral arterial oxygen content (CaO 2), cerebral extraction rate of oxygen (CERO 2), cerebral arteriovenous blood oxygen content difference (a-vDO 2)] were compared between the two groups before sedation and at 24, 48 and 72 hours of sedation. Results:① Among the 108 patients, 3 patients with cerebral hemorrhage received secondary surgery or had worsening of cerebral hernia were excluded. 105 patients were enrolled in the study, including 54 patients in the EGDS group and 51 patients in the on-demand sedation group. There were no statistically significant differences in gender, age, type of craniocerebral injury, GCS score, proportion of mechanical ventilation and operation ratio between the two groups. ② Compared with before sedation, Lac, CERO 2 and a-vDO 2 of both groups gradually reduced over time of sedation while SjvO 2 and CaO 2 were gradually higher. Those changes were more quickly in the EGDS group, Lac, SjO 2, CERO 2 and a-vDO 2 significantly improved at 24 hours of sedation compared with those before sedation. Above indexes at 72 hours of sedation in the EGDS group were obviously better than those in the on-demand sedation group [Lac (mmol/L): 1.81±0.31 vs. 2.19±0.12, SjvO 2: 0.714±0.125 vs. 0.683±0.132, CaO 2 (mL/L): 201.21±15.25 vs. 179.65±14.07, CERO 2: (27.87±3.66)% vs. (33.00±2.58)%, a-vDO 2 (mL/L): 44.32±5.68 vs. 48.57±8.22, all P < 0.05]. ③ Compared with before sedation, HR, MAP and ICP decreased in the two groups over time while CPP, BIS and GCS score showed increasing trend, especially more quickly in the EGDS group, HR at 24 hours of sedation, MAP, CPP, BIS and GCS score at 48 hours significantly improved as compared with those before sedation. Hemodynamics and sedation related parameters and GCS score at 72 hours of sedation in the EGDS group were significantly better than those in the on-demand sedation group [HR (bpm): 70.69±7.80 vs. 79.85±9.77, MAP (mmHg, 1 mmHg = 0.133 kPa): 84.23±8.76 vs. 89.97±9.48, ICP (mmHg): 14.23±8.76 vs. 15.97±9.48, BIS: 60.56±24.58 vs. 56.86±33.44, GCS score: 8.06±3.63 vs. 7.86±2.98, all P < 0.05]. The APACHE Ⅱ scores were significantly reduced at 72 hours of sedation in both groups as compared with those before sedation, while there was no statistical difference between the two groups. Conclusion:Compared with the on-demand sedation, EGDS could reduce cerebral oxygen metabolism, improve the coma degree, and reduce the severity of the disease in patients with acute brain injury.

Objective:To evaluate the effect of lower limb neuromuscular electrical stimulation (NMES) on mechanical ventilation patients in intensive care unit (ICU).Methods:Databases including the Cochrane Library, PubMed, Web of Science, Embase, SinoMed, CNKI, VIP and Wanfang database were searched from inception to May 2021. Randomized controlled trails (RCT) about the influence of NMES of lower limbs in patients with mechanical ventilation in ICU were collected. Routine rehabilitation measures were implemented in the control group, while the combination of routine rehabilitation and NMES on the lower limbs was implemented in the observation group. The literature screening, data extracting, and bias risk assessment of included studies were conducted independently by two reviewers. RevMan 5.3 software was used to perform Meta-analysis. Funnel plot was used to test publication bias.Results:A total of 8 RCT were eventually enrolled. The literature quality evaluation results showed that 1 study was grade A and 7 studies were grade B, suggesting that the quality of the included literature was relatively high. The Meta-analysis results showed that NMES in the lower extremities could effectively shorten the duration of mechanical ventilation in ICU patients [standardized mean difference ( SMD) = -0.51, 95% confidence interval (95% CI) was -0.72 to -0.31, P < 0.000 01], increase the maximum inspiratory pressure [MIP; mean difference ( MD) = 14.19, 95% CI was 9.30 to 19.09, P < 0.000 01], and improve the functional status of critically ill patients [functional status score for ICU (FSS-ICU); MD = 10.44, 95% CI was 3.12 to 17.77, P = 0.005] with statistically significances. However, there were no significant advantages in increasing the Medical Research Council (MRC) score ( MD = 2.13, 95% CI was -1.38 to 5.63, P = 0.23), reducing ICU mortality [relative risk ( RR) = 0.80, 95% CI was 0.51 to 1.24, P = 0.31], shortening length of ICU stay ( MD = -0.54, 95% CI was -3.67 to 2.59, P = 0.74), and the combined effect was not statistically significant. Funnel plot based on the duration of mechanical ventilation showed that the distribution of included articles was basically symmetrical, and no publication bias was detected. Conclusions:NMES of the lower limbs can not only shorten the ventilation duration effectively, but also improve the MIP and functional status of mechanically ventilated patients in ICU. However, it has no significant effect on the MRC score, ICU mortality and length of ICU stay of patients with mechanical ventilation. In the future, high-quality, large sample size and multi-center RCT are needed to verify the effects of NMES.

Objective:To explore the clinical significance of biopsy pathological examination of cervical cytology negative, high-risk human papillomavirus (HPV) positive.Methods:The pathological data of cervical biopsy in 220 patients with cytological negative, HPV16/18 positive or interval of 1 year other 12 high-risk HPV (12HR-HPV) lasting positive for more than 1 year from January 2014 to May 2019 were retrospectively analyzed.Results:Of 220 patients, there were 3 cases with adenocarcinoma, 18 cases with CINⅢ, 18 cases with CINⅡ, 69 cases with CINⅠ, 47 cases with condyloma-like lesions, 65 cases of chronic inflammation.Among 36 cases of high-grade squamous intraepithelial lesions, there were 35 cases with HPV16/18 positive, accounting for about 15.91%(35/220), and only 1 case of other 12 high-risk HPV was continuously positive for more than one year, accounting for 0.45%(1/220).Conclusion:Cervical cytological screening may appear false negative, high-risk HPV typing examination may be more able to detect cervical intraepithelial lesions, for cytological negative, high-risk HPV positive, especially HPV16/18 positive, immediate referral colposcopy can reduce the missed diagnosis of cervical high-grade squamous intraepithelial lesions and even cancerous.