To introduce and analyze guideline terminology related to clinical question formulation, evidence retrieval and appraisal, and recommendation development.

Objective:To review the clinical status based on the best evidence of drug administration in patients with dysphagia, systematically analyze the obstacle factors and promoting factors in the process of evidence transformation, and formulate reform strategies.Methods:Based on the evidence-based nursing research method and the guidance of the Ottawa Model of Research Use (OMRU), the review indicators were developed based on the best evidence. The current status of clinical practice behaviors of 223 patients and 75 nurses in the Neurology, Neurosurgery and Geriatric departments of the Affiliated Hospital of Jiangsu University were reviewed from July to December 2021.Based on the results of the review, qualitative interviews were conducted with 32 potential adopters, and content analysis was used to assess the barriers and contributing factors to the clinical translation of evidence in three aspects: evidence-based change, potential adopters and practice environment, so as to develop effective strategies.Results:Based on the 22 best evidence selected, the evidence-based team developed 25 review indicators to carry out clinical review, showing that the compliance rate of 16 indicators were less than 60%. By analyzing and summarizing the interview results of potential adopters, the main obstacles leading to the low compliance rate of nurses were analyzed as follows: evidence-based reform changed the traditional work mode, and the application of evidence was not convenient; at the level of potential adopters, nurses had poor knowledge and practice, heavy work burden, and low awareness of patients and caregivers; at the level of practice environment, there was lack of nursing norms and procedures for clinical transformation of evidence, and the channels of multi-disciplinary collaboration and communication were not smooth. The main promoting factors were the perfect supervision mechanism of evidence-based nursing projects, the evidence-based group had rich experience in evidence transformation, the management was willing to change, and the practitioners were good at innovation.Conclusions:There is still a large gap between the clinical practice and the best evidence of drug administration in patients with dysphagia. The promoting factors should be fully utilized to overcome the obstacles and implement improvements to promote the effective transformation of evidence into clinical practice.

Purpose: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. Materials and Methods: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. Results: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients. Conclusion In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

Phosphatidylinositol-3-kinase (PI3K) inhibitors can increase the sensitivity of tumor cells to Poly ADP-ribose polymerase-1 (PARP-1) inhibitors. Therefore, the simultaneous inhibition of the PARP-1 and PI3K activities are expected to overcome the drug resistance of PARP-1 inhibitors.In our previous work, two compounds XW-1 and WZ-1 with excellent activities against PARP-1 and PI3K were obtained with the limitation to further study due to their poor water solubility.Therefore, XW-1 and WZ-1 were chosen as lead compounds to optimize their solubility by introducing a salt-forming site via a urea group, and 11 novel compounds were designed and synthesized. The structure of all target compounds was confirmed by 1H NMR, 13C NMR, and HRMS.The enzyme activities of the compounds against PARP-1 and PI3K were measured, and the results showed that most of the compounds demonstrated good inhibitory activities against PARP-1 and PI3K.Based on the above result, the inhibitory activities of compounds 8b, 8e, and 8f against MDA-MB-231, MDA-MB-468, HCC1937, HCT116, and olaparib-resistant HCT116R were determined by MTT, respectively.Additionally, the structure-activity relationship was discussed. The results showed that these compounds displayed excellent antiproliferation activity.Among them, compound 8f demonstrated antiproliferation remarkably against all five tumor cells, which was more potent than that of olaparib, and was comparable to that of BKM120.Furthermore, the solubility of hydrochloride salts of compound 8b and 8f was significantly improved compared to the lead compounds.The results of this study will provide a theoretical basis for the further development of PARP-1 and PI3K dual-target inhibitors with good pharmaceutical properties and strong inhibitory activities.

Objective:To investigate the protective effect of human umbilical cord mesenchymal stem cell conditioned medium (HucMSC-cm) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and relevant mechanism of action.Methods:Forty 6-week-old male C57BL/6 mice were selected and randomized (random number) into the sham group, LPS group, LPS + HucMSC-cm (LPS+cm) group, and LPS+HucMSC-cm+Compound C (LPS+cm+cc) group, with 10 mice in each group. Mice were intratracheally injected with LPS (5 mg/kg) to establish ALI model, and intratracheally injected with hucMSC-CM (50 μL) 4 h after LPS treatment. Mice in the LPS+cm+cc group were intraperitoneally treated with Compound C (15 mg/kg) prior to LPS treatment. Neutrophils in peripheral blood were counted with the automated hematology analyzer 72 h after LPS administration. After that, mice were sacrificed, and the lung tissue pathology was observed using hematoxylin eosin (HE) staining. Besides, the expressions of IL-6, ICAM-1, VCAM-1 and P-AMP-activated protein kinase (P-AMPK) in the lung tissues were analyzed by Western blot and immunohistochemical assay. In vitro, human lung microvascular endothelial cells (HuLEC-5a) were cultured and divided into three groups: control group, LPS group (10 μg/ mL), and LPS + HucMSC-cm group. After 24 h of treatment, the expressions of p-AMPK and AMPK were detected by Western blot, and the expressions of IL-6 and IL-8 were detected by real-time fluorescence quantitative PCR. Oneway analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between two groups were performed using the Tukey’s multiple comparison test. Results:Compared with the sham group, the LPS group showed lungs with congestion and swelling, thickened pulmonary septum, and inflammatory cell infiltration. Moreover, in the LPS group, the protein expressions of IL-6 ( P=0.003), ICAM-1 ( P<0.001) and VCAM-1 ( P=0.001) were increased significantly, while the expression of p-AMPK was decreased ( P=0.013), accompanied by an increase in the proportion of neutrophils in peripheral blood ( P<0.001). Compared with the LPS group, the LPS+HucMSC-cm group demonstrated eased congestion, edema and pathological injury of lung tissue, reversed protein expressions of IL-6 ( P=0.003), ICAM-1 ( P=0.002), VCAM-1 ( P=0.006) and P-AMPK ( P=0.002), as well as decreased proportion of neutrophils in peripheral blood ( P<0.005). Compared with the LPS+HucMSC-cm group, the LPS+cm+cc group exhibited more severe lung histopathological injury, significantly increased protein expressions of IL-6, ICAM-1 and VCAM-1 in lung tissues, as well as decreased expression of P-AMPK protein. The results of immunohistochemistry were consistent with those of protein. In vitro experiment, after LPS treatment, the mRNA expressions of IL-6 ( P<0.001) and IL-8 ( P=0.027) were increased and p-AMPK protein expression ( P=0.005) was decreased as compared with the control group. In comparison with the LPS group, the LPS+HucMSC-cm group showed decreased mRNA expression levels of IL-6 ( P=0.003) and IL-8 ( P=0.002), but increased protein level of p-AMPK ( P=0.003). Conclusions:HucMSC-cm has a protective effect against LPS-induced acute lung injury, which is mainly attributed to the inhibited expression of adhesion molecules and inflammatory factors under the activation of AMPK.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To understand the status of sedation and analgesia treatment and management in pediatric intensive care unit(PICU) in Shandong Province, and to provide the basis for the improvement of sedation and analgesia treatment plan.Methods:This study was a multi-center retrospective study.The PICUs of 6 tertiary hospitals in Shandong Province participated in this study.The data of 1 340 children admitted to these 6 PICUs from January 2016 to December 2018 were collected.The age, gender, the pediatric risk of mortality score Ⅲ at 24 hours after admission, whether they received mechanical ventilation, whether they received sedation and(or) analgesia, whether they were monitored sedation and(or) analgesia, and in-hospital mortality were analyzed.The children were divided into the simple sedation group( n=798), the sedation + analgesia group( n=120) and the non-sedation analgesia group( n=422) according to whether they received sedation and(or) analgesia.The diseases, proportion of mechanical ventilation, incidence of hypotension, average length of stay in PICU and in-hospital mortality were compared among the three groups. Results:The median age of the 1 340 children was (13.3±6.4) months, including 786 males(58.7%). Sedation therapy had been carried out in 6 PICUs, of which 5 PICUs had routine sedation assessment; 4 PICUs had carried out analgesic therapy, of which only 2 had routine pain assessment.A total of 918 children(68.5%)received sedation and(or) analgesia, midazolam was the most commonly used sedative drug, followed by dexmedetomidine, and 526 children(57.3%)were monitored for sedation assessment, the most commonly used assessment method was the Richmond agitation sedation score.One hundred and twenty(9.0%)cases received sedation combined with analgesia, fentanyl was the most commonly used analgesic, and 38 children(31.7%) underwent routine pain assessment.There was no significant difference in age and sex among the three groups.The proportion of surgical diseases and patients received mechanical ventilation(100.0%, 120/120) were the highest in the sedation + analgesia group.The proportion of mechanically ventilated patients was the lowest in the non-sedation analgesia group(11.4%, 48/422). The mean duration of mechanical ventilation in the sedation + analgesia group was slightly shorter than that in the simple sedation group( P>0.05). The incidence of hypotension was highest in the sedation + analgesia group, and lowest in the non-sedation analgesia group[21.7%(26/120) vs.2.1%(9/422), P<0.01]. There was no significant difference in in-hospital mortality and mean PICU stay among three groups. Conclusion:Benzodiazepines are still the main sedative drugs used in PICUs in Shandong Province.In recent years, the usage of dexmedetomidine has gradually increased, but the proportion of analgesic use is very low.At present, analgesic and sedative therapy is mainly used for children after surgery and receiving mechanical ventilation.Although analgesic and sedative therapy does not increase the in-hospital mortality and average length of stay in PICU, it increases the incidence of hypotension.The sedative and analgesic treatment and assessment in the PICU of Shandong Province are still not standardized, mainly reflected in infrequently analgesic treatment and the assessment of sedation and pain, which need to be further improved.

Objective: To analyze the epidemiological characteristics of acute paraquat(PQ)poisoning in children in southwest Shandong, and the risk factors for pulmonary interstitial fibrosis. Methods: This retrospective study was performed on the clinical data of children with acute PQ poisoning admitted from January 2013 to December 2017 in 12 hospitals in southwest Shandong.All participants were divided into pulmonary interstitial fibrosis group and no pulmonary interstitial fibrosis group on the basis of the chest CT 14 days after poisoning.The epidemiological characteristics and risk factors of pulmonary interstitial fibrosis were analyzed. Results: During the study period, a total of 307 children with acute PQ poisoning were admitted to 12 hospitals, of which 61 (19.87%) were suffering from acute PQ poisoning.Forty-nine cases with complete clinical data were analyzed, including 26 male and 23 female patients poisoned by oral.The age distribution ranged from 8 months to 14 years.Poisoning mainly occured from July to September of each year.The mortality of acute PQ poisoning was 8.2%(4/49), and the incidence of pulmonary interstitial fibrosis in survival patients was 44.4%(20/45). Statistical differences (P<0.05) were found between the pulmonary interstitial fibrosis and no pulmonary interstitial fibrosis, with regard to the times of blood purification, the time from poison exposure to blood purification, the application rate of glucocorticoids, the concentration of PQ in urine, the pediatric critical illness score, the time from poison exposure to gastric lavage, the white blood count at admission, serum creatinine, arterial blood lactate, PaO₂, PaCO₂, and PaO₂/FiO₂; however, there was no significant difference in the proportion of blood purification treatment, the mode of blood purification treatment, alanine aminotransferase, aspartate aminotransferase, urea nitrogen, creatine kinase and troponin.Stepwise logistic regression analysis showed that the time from exposure to poison to gastric lavage(OR=0.683, 95%CI 0.210-2.222)and to blood purification(OR=0.0133, 95%CI 0.004-0.042), the times of blood purification(OR=2.862, 95%CI 1.450-5.648), concentration of PQ in urine(OR=1.435, 95%CI 1.085-1.898), and the use of glucocorticoids(OR=0.190, 95%CI 0.048-0.757) were the risk factors for pulmonary interstitial fibrosis(P<0.05). Conclusion Early gastric lavage and blood purification, increasing the frequence of adminitrating purification appropriately, using low-dose glucocorticoids can reduce the incidence of pulmonary interstitial fibrosis of children with acute PQ poisoning.

BACKGROUND: Changes in the center of body weight during standing reflects the structure, function and muscles of the lower limbs and even the whole body. The relationship between standing posture control and foot type, balance ability, and muscle activation is rarely reported. OBJECTIVE: To investigate the effects of natural, lean forward and lean backward standing on foot arch, body balance and muscle activation. METHODS: Fifteen subjects without foot lesions and diseases related to foot function were selected. Three-dimensional foot scanner was used to test and analyze the foot arch in three standing postures. BTS FREEMG 300 surface electromyography tester and balance tester were used to test and analyze the maximum root mean square of muscle and two balance ability indexes (envelope area and average velocity of center of gravity) in three standing postures. RESULTS AND CONCLUSION: (1) For height index of foot arch: there was significant difference between natural standing and forward standing (P ＜ 0.05). There was significant difference between natural standing and backward standing (P ＜ 0.05), but there was no significant difference between forward standing and backward standing (P＞ 0.05). (2) The degree of muscle activation was as follows: when standing naturally, the medial peroneal muscles＞ erector muscles＞ rectus abdominis＞ gluteus medius＞ biceps femoris＞ external oblique femoris＞ anterior tibial muscle＞ rectus femoris muscle＞ gluteus maximus muscle. During forward standing: the medial of the peroneal muscle＞ medius gluteus＞ vertical ridge＞ long head of biceps femoris＞ anterior tibial muscle＞ rectus abdominis muscle＞ gluteus maximus. During backward standing: the obliquus externus femur＞ rectus femoris＞ long head of biceps femoris＞ erector spinae＞ musculus rectus abdominis＞ the medial of the peroneal muscle＞ gluteus medius＞ gluteus maximus. (3) Balance: there was no significant difference between natural standing and forward standing (P＞ 0.05); there was significant difference between natural standing and backward standing (P ＜ 0.05), but there was no significant difference between forward standing and backward standing (P＞ 0.05). (4) In summary, it is easy to maintain body stability at low muscle activation intensity when the human body is standing naturally. During the body backward standing, the muscle activation intensity is highest due to instability. When the center of gravity moves forward and backward, the contralateral muscle is mainly activated. The arch of the foot rises when it leans forward and backward. The slight anterior and posterior movements of the center of gravity in the standing posture can lead to changes in muscle activation degree and balance control.

Objective To investigate the diagnostic value of the partial least square discriminant analysis (PLS-DA) model based on seven serum cytokines for children patients with mycoplasma pneumonia,the 7 cytokines includ interleukin-2 (IL-2),IL-4,IL-6,IL-8,IL-10,tumor necrosis factor alpha (TNF-α) and interferonγ(IFN-γ).Methods Serum levels of cytokines were measured by the double antibody sandwich method of ELI-SA in 140 patients with pneumoniae infection and 135 normal healthy controls,and data was analyzed with the receiver operation characteristic (ROC) curve and the PLS-DA.Results The area under the ROC curve (AUC) of serum IL-10 and IFN-γfor the diagnosis of MPP was 0.84 (95％ CL:0.79 ～ 0.89).The sensitivity of IL-10 and IFN-γ for the diagnosis of MPP was 91.4％ and 82.1％,with the specificity was 77.0％ and 82.2％,respectively.The diagnostic accuracy of the PLS-DA model based on seven serum cytokines for children MPP and the controls was 90.0％ and 88.15％,and the prediction accuracy was 86.4％ and 87.4％,respectively.Conclusion Seven serum cytokines based on PLS-DA model was helpful for the diagnosis of children patients with MPP.