Objective:Care bundles for critically ill patients with early enteral nutrition up to goal was constructed. Its purpose was to improve early enteral nutrition, prognosis and provide reference basis for improving the rate of standard of early enteral nutrition in critically ill patients.Methods:By conducting systematic searching of domestic and foreign Chinese and English databases, related guide websites, relevant documents on early enteral nutrition in critically ill patients up to goal, which were obtained, evaluated, extracted, summarized and graded. After discussion by the research group, the first draft was prepared. Delphi method was used to conduct two rounds of expert correspondence, and the final draft of the proposal was established through the reliability analysis of correspondence results.Results:Twenty experts participated finally, and their opinions tended to be consistent after two rounds of expert inquiry. The authority coefficients were 0.92 and 0.91 respectively. The variation coefficients of the importance and operability of the two rounds of correspondence items were 0.05-0.20 and 0.05-0.21, 0.00-0.17 and 0.00-0.20 respectively. The Kendall concordance coefficients for the importance and operability of the two rounds of correspondence items were 0.16 and 0.13, 0.27 and 0.18 respectively. The differences were statistically significant ( χ2 values were 117.01-228.43, all P<0.05). Finally, the final draft of bundle of care for early enteral nutrition up to goal in critically ill patients was established which included three aspects related to evaluation, implementation, and effectiveness monitoring, besides care bundle included 12 intervention perspectives and 29 specific intervention measures. Conclusions:Based on evidence-based and delphi method constructing care bundles for critically ill patients with early enteral nutrition up to goal was scientific, reliable and practical which could provide theoretical and practical guidance for bundled nursing interventions to meet early enteral nutrition standards in critically ill patients.

BACKGROUND:A large number of studies have investigated the effects of whole body vibration training at different frequencies on muscle strength,but less is reported on the differences in the efficacy of vibration training at different frequencies on patellar tendinopathy. OBJECTIVE:To explore the effect of eccentric training of quadriceps combined with different frequency of whole body vibration training on patellar tendinopathy. METHODS:From April to June 2022,48 patients with patellar tendinopathy were recruited from Wuhan Sports University and randomly divided into eccentric training group(n=12),30 Hz group(n=12),40 Hz group(n=12),and 50 Hz group(n=12).The eccentric training group only completed eccentric training of the quadriceps.The 30 Hz,40 Hz and 50 Hz groups performed the whole body vibration training with the amplitude of 2 mm and frequencies of 30 Hz,40 Hz and 50 Hz respectively on the basis of the eccentric training of the quadriceps.The intervention lasted for 8 weeks,three times a week.Before and after the intervention,the patients'surface electromyography signals of the quadriceps,kinematics and dynamics data of knee joint at the time of landing in deep jump and the time of peak vertical ground reaction,Visual Analogue Scale score,Victorian Institute of Sports Assessment-Patellar score were evaluated. RESULTS AND CONCLUSION:After 8 weeks of intervention,compared with the eccentric training group,the median frequency of the lateral and medial femoris muscles were significantly higher in the 40 Hz and 50 Hz groups(P＜0.05).At the time of landing,the knee joint flexion angle and external rotation moment in the 40 Hz and 50 Hz groups were significantly lower than those in the eccentric training group(P＜0.05),while the knee joint flexion angle in the 50 Hz group was significantly lower than that in the 30 Hz group(P＜0.05).At the peak moment of vertical ground reaction,the knee extension torque in the 40 Hz group was significantly lower than that in the eccectric training group(P＜0.05);the knee flexion angle and knee extension torque in the 50 Hz group were significantly lower than those in the eccentric training group(P＜0.05).The Visual Analogue Scale scores in the 50 Hz and 40 Hz groups were significantly lower than those in the eccentric training group(P＜0.05).The Victorian Institute of Sports Assessment-Patellar score in the 50 Hz group was significantly higher than that in the eccentric training group and 30 Hz group(P＜0.05).To conclude,eccentric training of the quadriceps combined with 50 Hz whole body vibration training can significantly improve quadriceps'strength,endurance and activation rate of the vastus lateralis muscle,reduce the pain of knee joint,and improve the function of the knee joint in patients with patellar tendinopathy.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Internal injury of seven emotions is an important proposition in etiology of traditional Chinese medicine.In view of the urgent social problem of brain aging,our research group put forward the hypothesis that"Liver failing to facilitate the coursing of Qi caused by long-term accumulation of negative emotions accelerates the process of brain aging".Firstly,establish the rat model of long-term negative emotional stress by indirect electric shock,and create films that induce anger.Secondly,through the perspective of animal experiments,case-control and normal population,it is revealed that the long-term accumulation of either single negative emotion(anger)or compound negative emotion can accelerate the process of brain aging and its mechanism.It also found the possibility biological basis of excessive and insufficient of liver catharsis in traditional Chinese medicine,and deepened the understanding of the individual differences of liver Zang Xiang syndrome and physiological function.Finally,with the help of event-related potentials(ERPs)and functional magnetic resonance imaging(fMRI),it is found that the potential objective diagnostic indexes of mild cognitive impairment(MCI)patients with long-term liver qi stagnation,and Liver Soothing method can improve their cognitive function,and reveal its therapeutic mechanism.The above research is helpful to make up for the defects of target emotion induction,improve the TCM etiology and pathogenesis theory of brain aging,provide possible biological indexes for early warning of diseases induced by abnormal of liver facilitate the coursing of Qi,and provide reference for early screening,diagnosis and treatment of MCI.

Objective:To investigate the prognosis and influencing factors in critically ill surgical patients of different feeding intolerance trajectories.Methods:The retrospective cohort study was conducted. The clinical data of 354 critically ill surgical patients who were admitted to 69 medical centers in the Chinese Critical Care Nutrition Trials Group -NEED database from March 2018 to July 2019 were selected. There were 247 males and 107 females, aged 58(46,68)years. According to the trajectory model of feeding intolerance change, 354 patients were divided into 3 categories as feeding intolerance, decreased feeding intolerance, continuous feeding intolerance, including 164, 49, 141 cases respectively. Observation indicators: (1) general situations of patients of different feeding intolerance trajectories; (2) treatment of patients of different feeding intolerance trajectories; (3) survival of patients of different feeding intolerance trajectories; (4) analysis of pro-gnostic factors in critically ill surgical patients. Measurement data of normal distribution were expressed as Mean± SD, and one-way analysis of variance was used for comparison between groups. Measurement data of skewed distribution were expressed as M( Q1, Q3), and Kruskal-Wallis rank sum test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and chi-square test was used for comparison between groups. Ordinal data were compared using the Kruskal-Wallis rank sum test. Bonferroni correction was used for pairwise comparison. Group-based trajectory model was constructed according to Traj plug-in in Stata17.0 statistical software, and the optimal trajectory model was evaluated by Bayesian information criterion and average posterior probability parameter. The Kaplan-Meier method was used to draw the survival curve and calculate the survival rate, and Log-Rank test was used for survival analyses. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. Results:(1) General situations of patients of different feeding intolerance trajectories. Of 354 critically ill surgical patients, 257 cases underwent enteral nutrition and 97 cases underwent enteral plus parenteral nutrition. The acute physiological and chronic health score (APACHEII) was 17(13,21), and the sequential organ failure score (SOFA) was 6(5,8). The modified Critical Illness Nutritional risk score (mNUTRIC) was 4 (2,5), the number of complications was 2(1,3). There were 293, 55 and 6 patients with grade Ⅰ, grade Ⅱ and grade Ⅲ acute gastrointestinal injury (AGI), and there were 224, 17 and 61 patients who were treated with mechanical ventilation, continuous renal replacement therapy and vasoactive drugs, respectively. The incidence of feeding intolerance in 354 patients increased first and then decreased, reaching a peak of 25.42%(90/354) on the third day and 53.67%(190/354) within 7 days. Of 354 critically ill surgical patients, cases with no feeding intolerance, decreased feeding intolerance, continuous feeding intolerance had the APACHE Ⅱ as 16(12,20), 17(14,25), 18(13,22), mNUTRIC as 3(2,5), 4(3,6), 4(3,5), the number of complications as 2(1,2), 2(2,3), 2(2,3). There were 152, 27, 114 cases with grade Ⅰ AGI, 12, 22, 27 cases with grade Ⅱ-Ⅲ AGI, 95, 39, 90 cases with mechanical ventilation. There were significant differences in the above indicators among the three groups ( H=6.14, 13.11, 28.05, χ2=37.96, 7.65, P< 0.05). Further analysis showed that compared with patients with no feeding intolerance, patients with decreased feeding intolerance and continuous feeding intolerance had the higher number of complications and grade of AGI ( Z=60.32, 54.69, χ2=39.72, 9.52, P<0.05), patients with decreased feeding intolerance had the higher mNUTRIC scores and ratio of mechanical ventilation ( Z=53.41, χ2=7.59, P<0.05). (2) Treatment of patients of different feeding intolerance trajectories. Cases with prokinetic drugs use and post-pyloric feeding were 36, 13 of patients with no feeding intolerance, 25 and 10 of patients with decreased feeding intolerance, 46 and 19 of patients with continuous feeding intolerance, respectively, showing significant differences in the above indicators among the three groups ( χ2=15.76, 6.20, P<0.05). Further analysis showed that compared with patients with no feeding intolerance, patients with decreased feeding intolerance had higher ratio of prokinetic drugs use and ratio of post-pyloric feeding ( χ2=15.60, 6.10, P<0.05). (3) Survival of patients of different feeding intolerance trajectories. The 28-day overall survival rates of patients with no feeding intolerance, decreased feeding intolerance, and continued feeding intolerance were 96.96%, 95.92%, and 87.94%, respectively, showing a significant difference ( χ2=10.39, P<0.05). Further analysis showed a significant difference between patents with no feeding intolerance and patients with continuous feeding intolerance ( χ2=9.19, P<0.05). (4) Analysis of prognostic factors in critically ill surgical patients. Multivariate analysis showed that continuous feeding intolerance was an independent risk factor for 28-day death in critically ill surgical patients ( hazard ratio=3.92, 95% confidence interval as 1.43-10.79, P<0.05). Conclusion:For surgical critically ill patients, patients with continuous feeding intolerance have a higher 28-day mortality than patients with no feeding intolerance, and the continuous feeding intolerance is an independent risk factor for 28-day death in critically ill surgical patients.

ObjectiveTo explore the possible peripheral analgesic mechanism of electroacupuncture （EA） at promimal and distal acupoints in treatment of myofascial pain syndrome （MPS）. MethodsTwenty-four SD rats were randomly divided into blank group， model group， proximal group， and distal group， with six rats in each group. MPS model was prepared by “strike combined with centrifugal exercise” in all groups except for the blank group. After modeling， the rats in the proximal group received EA at the local myofascial trigger points （MTrPs）， namely the Ashi points， with dilatational waves of frequency of 2/100 HZ and voltage of 2-4 V， current intensity depending on a slight trembling of the left lower limbs， once a day， 15min each time，for 14 days. The rats in the distal group received EA at “Yanglingquan” （GB 34） and “Yinlingquan” （SP 9）， with the same operations as the proximal group. The rats in the blank group and the model group were only grasped and hedged， without other interventions. After intervention， the paw withdrawl mechanical threshold （PWMT） was measured， and variability between the left and right hind paws was calculated. Musculoskeletal ultrasound imaging and electromyography monitoring were performed on the left lower extremity vastus medialis. The morphological changes of vastus medialis muscle of the left lower extremity were observed by HE staining. The positive expression of substance P （SP）， calcitonin gene-related peptide （CGRP）， CD68 and CD206 in muscle tissue was detected by immunohistochemistry. Abdominal aortic serum interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and interleukin-8 （interleukin-8） were detected by ELISA. ResultsCompared to those in the blank group， the fibers of the vastus medial muscle of the rats in the model group were broken and distorted with thickness in variation， and the myofascia was broken， with fibrillation potential， enlarged muscle cells， inward moved nucleus， and widened muscle space； the variability of PWMT between the left and right hind paws significantly increased， as well as the levels of SP， CGRP， CD68， and CD206 in the vastus medialis muscle （P＜0.01）， and the serum IL-8 and TNF-αlevels were significantly elevated （P＜0.05 or P＜0.01）. Compared to those in the model group， the muscle fibers in the proximal and distal group were complete in shape and arranged in an orderly manner， with continued non-broken myofascia， regular shape of muscle cells， and significantly reduced level of IL-8 （P＜0.01）； the amplitude and frequency of spontaneous discharge in the proximal group significantly decreased， as well as the variability of PWMT between the left and right hind paws， and the levels of SP， CGRP， and CD68 in the vastus medialis muscle， while the CD206 level increased significantly （P＜0.05 or P＜0.01 ）； there was complex discharges in the distal group， with significantly decreased level of CD68 in the vastus medialis muscle and increased level of CD206 （P＜0.01）. Compared to the proximal group， the level of IL-8 in the distal group was significantly higher （P＜0.05）. ConclusionsEA at proximal acupoints can significantly improve the pain threshold and local muscle tissue morpho-logy in rats， and its mechanism may be related to reducing the levels of pain-causing substances and related inflammatory factors and promoting the polarization of macrophages. The analgesic effect of EA at distal acupoints is not obvious， and the mechanism is still unclear.

Objective:To explore the construction and effect of biobank in biological research in nursing field.Methods:Through the establishment of a biological research plan for nursing in Affiliated Jinhua Hospital, Zhejiang University School of Medicine, the biobank in biological research for nursing was constructed from aspects of biological samples, instruments and equipment, operating software, biobanking team formation, personnel training and standardized process formulation.Results:In August 2020, the Nursing Department and Central Laboratory of Affiliated Jinhua Hospital, Zhejiang University School of Medicine established a biobank for biological research in the nursing field, formed a biobank team, conducted personnel training and formulated standardized procedures. From December 1, 2020 to June 30, 2021, biological samples were collected from 264 gastric cancer patients and 56 healthy controls, mainly including whole blood, serum and urine.Conclusions:The construction of biobank for biological research in nursing field can collect abundant biological samples, which lays a foundation for subsequent independent biological research in nursing field.

Objective:To investigate the role of cholinergic anti-inflammatory pathway in the regulation of peptide transporter 1 (PepT1) expression in small intestinal epithelium of septic rats by Ghrelin.Methods:One hundred adult male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, sepsis+vagotomy group, sepsis+Ghrelin group, and sepsis+vagotomy+Ghrelin group, with 20 rats in each group. In the sham operation group, the cecum was separated after laparotomy, without ligation and perforation. In the sepsis group, the rats received cecal ligation puncture (CLP). In the sepsis+vagotomy group, the rats received CLP and vagotomy after laparotomy. In the sepsis+Ghrelin group, 100 μmol/L Ghrelin was intravenously injected after CLP immediately. The rats in the sepsis+vagotomy+Ghrelin group received CLP and vagotomy at the same time, then the Ghrelin was intravenously injected immediately with the same dose as the sepsis+Ghrelin group. Ten rats in each group were taken to observe their survival within 7 days. The remaining 10 rats were sacrificed 20 hours after the operation to obtain venous blood and small intestinal tissue. The condition of the abdominal intestine was observed. The injury of intestinal epithelial cells was observed with transmission electron microscopy. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum and small intestinal tissue were detected by enzyme-linked immunosorbent assay (ELISA). The brush border membrane vesicle (BBMV) was prepared, the levels of mRNA and protein expression of PepT1 in the small intestinal epithelium were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:All rats in the sham operation group survived at 7 days after operation. The 7-day cumulative survival rate of rats in the sepsis group was significantly lower than that in the sham operation group (20% vs. 100%, P < 0.05). The cumulative survival rate of rats after Ghrelin intervention was improved (compared with sepsis group: 40% vs. 20%, P < 0.05), but the protective effect of Ghrelin was weakened after vagotomy (compared with sepsis+Ghrelin group: 10% vs. 40%, P < 0.05). Compared with the sham operation group, in the sepsis group, the small intestine and cecum were dull red, the intestinal tubules were swollen and filled with gas, the intestinal epithelial cells were seriously injured under transmission electron microscopy, the levels of TNF-α and IL-1β in serum and small intestinal were significantly increased, and the expression levels of PepT1 mRNA and protein in the small intestinal epithelium were significantly decreased. It indicated that the sepsis rat model was successfully prepared. After vagotomy, the intestinal swelling and gas accumulation became worse in septic rats, leading to the death of all rats. Compared with the sepsis group, the abdominal situation in the sepsis+Ghrelin group was improved, the injury of intestinal epithelial cells was alleviated, the serum and small intestinal TNF-α and IL-1β were significantly decreased [serum TNF-α (ng/L): 253.27±23.32 vs. 287.90±19.48, small intestinal TNF-α (ng/L): 95.27±11.47 vs. 153.89±18.15, serum IL-1β (ng/L): 39.16±4.47 vs. 54.26±7.27, small intestinal IL-1β (ng/L): 28.47±4.13 vs. 42.26±2.59, all P < 0.05], and the expressions of PepT1 mRNA and protein in the small intestinal epithelium were significantly increased [PepT1 mRNA (2 -ΔΔCt): 0.66±0.05 vs. 0.53±0.06, PepT1 protein (PepT1/GAPDH): 0.80±0.04 vs. 0.60±0.05, both P < 0.05]. Compared with the sepsis+Ghrelin group, after vagotomy in the sepsis+vagotomy+Ghrelin group, the effect of Ghrelin on reducing the release of inflammatory factors in sepsis rats was significantly reduced [serum TNF-α (ng/L): 276.58±19.88 vs. 253.27±23.32, small intestinal TNF-α (ng/L): 144.28±12.99 vs. 95.27±11.47, serum IL-1β (ng/L): 48.15±3.21 vs. 39.16±4.47, small intestinal IL-1β (ng/L): 38.75±4.49 vs. 28.47±4.13, all P < 0.05], the up-regulated effect on the expression of PepT1 in small intestinal epithelium was lost [PepT1 mRNA (2 -ΔΔCt): 0.58±0.03 vs. 0.66±0.05, PepT1 protein (PepT1/GAPDH): 0.70±0.02 vs. 0.80±0.04, both P < 0.05], and the injury of small intestinal epithelial cells was worse. Conclusion:Ghrelin plays a protective role in sepsis by promoting cholinergic neurons to inhibit the release of inflammatory factors, thereby promoting the transcription and translation of PepT1.

Objective:To explore the feasibility of predicting TP53 mutation risk by immunohistochemical staining (IHC) pattern of P53 in Chinese diffuse large B-cell lymphoma (DLBCL) and its correlation with a prognostic difference.Methods:Between January 2021 and December 2021, 51 DLBCL cases at Beijing Boren Hospital were gathered. These cases had both IHC and next-generation sequencing (NGS) results. IHC classified the P53 protein expression pattern into a loss (<1% ) , diffuse (>80% ) , and heterogeneous (1% -80% ) . The sensitivity and specificity of the predicting TP53 mutation by IHC were assessed by comparing the results of the NGS, and the TP53 high mutation risk group included both loss and diffuse expression of P53. From June 2016 to September 2019, Peking University Cancer Hospital collected 131 DLBCL cases with thorough clinicopathological and follow-up data. From their tumor blocks, tissue microarray blocks were made for IHC evaluation of P53 expression pattern, and prognosis effect of P53 studies.Results:Among 51 cases with both IHC and NGS results, 23 cases were classified as TP53 high mutation risk (7 cases loss and 16 cases diffuse) , 22/23 cases were proved with mutated TP53 by NGS. Only 1 of the 28 cases classified as TP53 low mutation risk was proved with mutated TP53 by NGS. IHC had a sensitivity and specificity of 95.7% and 96.4% for predicting TP53 mutation. NGS identified a total of 26 TP53 mutations with a mutation frequency of 61.57% (13.41% -86.25% ) . In the diffuse group, 16 missense mutations and 2 splice mutations were detected; 6 truncating mutations and 1 splice mutation were detected in the loss group; 1 truncating mutation was detected in the heterogeneous group. Multivariate analysis demonstrated that TP53 cases with high mutation risk have impartial adverse significance for the 131 patients included in survival analysis ( HR=2.612, 95% CI 1.145-5.956, P=0.022) . Conclusion:IHC of P53 exhibiting loss (<1% ) or diffuse (>80% ) pattern indicated TP53 high mutation risk, IHC can predict TP53 mutation with high specificity and sensitivity. TP53 high mutation risk is an independent predictor for adverse survival.

AIM: To study chronopharmacokinetics of helicid and its metabolites. METHODS: An HPLC-MS method for simultaneous determination of helicid and its three phase I metabolites were established and validated. At 8:00, 14:00 and 0:00, the rats were given helicid 50 mg/kg by gavage, respectively. Blood samples were collected from ophthalmic venous plexus. Then plasma concentration was measured. Pharmacokinetic behaviors of the original drug and its metabolites after administration at different time points were calculated and compared. RESULTS: This established HPLC-MS/MS method was successfully applied to simultaneous determination of helicid and its three metabolites in rat plasma after intragastric administration. Using AUC