Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Background::Renal ischemia-reperfusion (R-I/R) injury is the most prevalent cause of acute kidney injury, with high mortality and poor prognosis. However, the underlying pathological mechanisms are not yet fully understood. Therefore, this study aimed to investigate the role of N-myc downstream-regulated gene 2 ( Ndrg2) in R-I/R injury. Methods::We examined the expression of Ndrg2 in the kidney under normal physiological conditions and after R-I/R injury by immunofluorescence staining, real-time polymerase chain reaction, and western blotting. We then detected R-I/R injury in Ndrg2-deficient ( Ndrg2-/-) mice and wild type ( Ndrg2+/+) littermates in vivo, and detected oxygen and glucose deprivation and reperfusion (OGD-R) injury in HK-2 cells. We further conducted transcriptomic sequencing to investigate the role of Ndrg2 in R-I/R injury and detected levels of oxidative stress and mitochondrial damage by dihydroethidium staining, biochemical assays, and western blot. Finally, we measured the levels of mitophagy in Ndrg2+/+ and Ndrg2-/- mice after R-I/R injury or HK-2 cells in OGD-R injury. Results::Ndrg2 was primarily expressed in renal proximal tubules and its expression was significantly decreased 24 h after R-I/R injury. Ndrg2-/- mice exhibited significantly attenuated R-I/R injury compared to Ndrg2+/+ mice. Transcriptomics profiling showed that Ndrg2 deficiency induced perturbations of multiple signaling pathways, downregulated inflammatory responses and oxidative stress, and increased autophagy following R-I/R injury. Further studies revealed that Ndrg2 deficiency reduced oxidative stress and mitochondrial damage. Notably, Ndrg2 deficiency significantly activated phosphatase and tensin homologue on chromosome ten-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy. The downregulation of NDRG2 expression significantly increased cell viability after OGD-R injury, increased the expression of heme oxygenase-1, decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, and increased the expression of the PINK1/Parkin pathway. Conclusion::Ndrg2 deficiency might become a therapy target for R-I/R injury by decreasing oxidative stress, maintaining mitochondrial homeostasis, and activating PINK1/Parkin-mediated mitophagy.

In order to obtain a cell line which high expressed of rabies virus glycoprotein the produc-tion of rabies subunit vaccine,the RABV glycoprotein gene sequence was amplified by RT-PCR and cloned into the lentiviral expression vector.The recombinant plasmid pLV-RVG,envelope plasmid pMD2.0G and packaging plasmid psPAX2 were co-transfected into HEK-293T cells to harvest lentivirus and infect new HEK-293T cells.The 293T-RVG cell line was obtained by puro-mycin pressure screening.Indirect immunofluorescence assay(IFA)and Western blot showed that the 67 kD RABV-G protein was highly expressed in the cells.The neutralizing antibody titer reached 2.19 IU/mL within 14 days after immunization,which was higher than the internationally recognized protection threshold(0.5 IU/mL).This study showed that the cell line 293T-RVG with stable and high expression of rabies virus glycoprotein was successfully constructed.The cell line could protect mice against rabies virus challenge and could be used as a subunit vaccine with poten-tial for large-scale production and application.

Objective The purpose of writing the"Expert consensus on the prevention and control of intracranial hypertension in adult critical illness"(here in after referred to as the"Consensus")aimed to standardize the nursing work related to the prevention and control of elevated intracranial pressure in adult critical illness,and prevent the occurrence of complications such as cerebral herniation.Methods Guided by evidence-based practice,domestic and foreign databases were searched for guidelines,expert consensuses,systematic evaluation,evidence summaries,and original research related to increased intracranial pressure.The search period is from database establishment to March 2024.The high-quality evidence and suggestions in the field was evaluated,extracted,and summarized to form a preliminary consensus.27 experts were invited to conduct 2 rounds of expert inquiry and 8 experts were invited to conduct 2 expert discussion meetings,to revise and improve the content of the initial draft,and to ultimately form a final consensus.Results The effective response rates for both rounds of inquiry questionnaires were 100％,with expert authority coefficients of 0.884,judgment coefficients of 0.964,and familiarity levels of 0.804.The Kendall harmony coefficients for 2 rounds of inquiry were 0.107 and 0.083(P＜0.01),respectively.The consensus includes 4 aspects,including identification,monitoring,prevention and control strategies,emergency treatment and care for increased intracranial pressure.Conclusion This"Consensus"has strong scientific validity and can provide reference basis for nurses to carry out prevention and control of intracranial pressure increase.

Medication is a potential factor influencing frailty. However, the relationship between pharmaceutical treatments and frailty remains unclear. Therefore, we conducted the present systematic review to summarize the association between drug therapy and the risk of incident frailty in older adults. We systematically searched the MEDLINE electronic database for articles indexed between January 1, 2000, and December 31, 2021, for randomized controlled trials (RCTs) and cohort studies reporting frailty changes associated with drug therapy. A total of six RCTs and 13 cohort studies involving 211,948 participants were identified, and their treatments were categorized into six medication classes: analgesics, cardiometabolic medication, chemotherapy, central nervous system (CNS)-active medication, hormonal therapy, and nutritional supplements. While the analysis revealed that only CNS-active medications were associated with an elevated risk of frailty, other medication classes also affected frailty; however, this is not conclusively attributable to a class-wide effect.

Humans ; Rituximab/therapeutic use* ; Bendamustine Hydrochloride/therapeutic use* ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Lymphoma, B-Cell ; Protein Kinase Inhibitors/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Treatment Outcome

Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.

ObjectiveTo explore the difference of learning and memory function between permanent cerebral ischemia and ischemia-reperfusion rat models by filament-occluded method after three weeks of natural recovery, and to observe the changes of brain structure. MethodsA total of 21 SPF male Sprague-Dawley rats were randomly divided into sham group (n = 7), permanent ischemia group (n = 7) and ischemia-reperfusion group (n = 7). The latter two group underwent left middle cerebral artery occlusion, and the ischemia-reperfusion group was reperfused after 90 minutes of ischemia. All the rats were tested with Morris Water Maze 16 to 22 days after modeling, to record escape latency in the navigation experiment, as well as first latency, platform quadrant swimming time ratio and distance ratio, boundary swimming time ratio and distance ratio, average speed, and the swimming path in the space exploration experiment. On the 22nd day after modeling, four rats with similar Longa scores in each group were scanned by magnetic resonance by diffusion tensor imaging, to measure the fractional anisotropy (FA) of cerebral ischemic cortex, striatum, hippocampus and their corresponding contralateral regions, to calculate ratio of FA (rFA); as well as the volume of infarct (VI) and ratio of VI (rVI). ResultsFor navigation experiment, the escape latency decreased in all the groups with the time (F = 36.202, P < 0.001), but it was not significant for the permanent ischemia group (F = 4.004, P > 0.05). The escape latency was longer in the permanent ischemia group than in the other two groups at each time points (P < 0.05). For space exploration experiment, the boundary time ratio and distance ratio were more in the permanent ischemia group and the ischemia-reperfusion group than in the sham group (P < 0.017), and the first latency was longer in the permanent ischemia group than in the sham group (P < 0.017). The swimming path of ischemia-reperfusion group and sham operation group was better than that of the permanent ischemia group. FA and rFA in left cortex and striatum were less in the permanent ischemia group and the ischemia-reperfusion group than in the sham group (P < 0.05), while FA and rFA of left cortex and FA of left striatum were less in the permanent ischemia group than in the ischemia-reperfusion group (P < 0.05). The VI and rVI were larger in the permanent ischemia group than in the ischemia-reperfusion group (t > 4.185, P < 0.01). FA and rFA of left cortex and striatum correlated with escape latency, boundary time ratio and distance ratio (|r| > 0.498, P < 0.05). The VI and rVI correlated with escape latency and boundary time ratio (|r| > 0.538, P < 0.05). ConclusionCognitive impairment is more severe in the rat model of permanent cerebral ischemia, which may relate to the larger damage of structure of nerve fibers in ischemic cortex and striatum, and larger infarct size.

Objective:To establish a nomograph prediction model of early critical changes in children with febrile convulsion, and to provide guidance for the prevention and nursing of children with febrile convulsion.Methods:Convenient sampling method was adopted to select 384 children with febrile convulsion in Anhui Children ′s Hospital from January 2018 to April 2021 as the research objects. Based on pews, the children with febrile convulsion were divided into 334 cases of non risk group and 50 cases of risk group. Binary Logistic regression analysis were used to determine the independent risk factors affecting the early critical changes of children with febrile convulsion. A nomogram was drawn based on the independent risk factors. The discrimination and consistency of the model were verified by model ROC curve and Hosmer Lemeshow goodness of fit.The external validation of model prediction efficiency were verified by validation data. Results:Binary Logistic regression analysis showed that age, respiratory rhythm disorder, unconsciousness, breath rate, heart rate, neutrophil-to-lymphocyte ratio (NLR), red blood cell distribution width (RDW), duration of first convulsion and mean body temperature after first convulsion were influence factors for early critical changes in children with febrile convulsion ( P<0.05). The C-index of the model was 0.974 (95% CI 0.954-0.993), and the C-index of the external validation of the model was 0.922 (95% CI 0.880-0.966). The results of H-L fitting test showed that the difference was not statistically significant( χ2=0.29, P>0.05). Conclusions:The early critical changes of children with febrile convulsion may be affected by respiratory rhythm disorder, confusion of consciousness, breath rate, heart rate, NLR, RDW, duration of the first convulsion, mean temperature after the first convulsion and other factors. Pediatric emergency department should collect corresponding intervention measures for children with febrile convulsion according to the establishment of prediction model to prevent their early deterioration.

OBJECTIVE: To detect the Epstein-Barr virus (EBV) viral load of children after hematopoietic stem cell transplantation (HSCT) using chip digital PCR (cdPCR). METHODS: The sensitivity of cdPCR was determined using EBV plasmids and the EBV B95-8 strain. The specificity of EBV cdPCR was evaluated using the EBV B95-8 strain and other herpesviruses (herpes simplex virus 1, herpes simplex virus 2, varicella zoster virus, human cytomegalovirus, human herpesvirus 6, and human herpesvirus 7). From May 2019 to September 2020, 64 serum samples of children following HSCT were collected. EBV infection and the viral load of serum samples were detected by cdPCR. The epidemiological characteristics of EBV infections were analyzed in HSCT patients. RESULTS: The limit of detection of EBV cdPCR was 110 copies/mL, and the limit of detection of EBV quantitative PCR was 327 copies/mL for the pUC57-BALF5 plasmid. The result of EBV cdPCR was up to 121 copies/mL in the EBV B95-8 strain, and both were more sensitive than that of quantitative PCR. Using cdPCR, the incidence of EBV infection was 18.75% in 64 children after HSCT. The minimum EBV viral load was 140 copies/mL, and the maximum viral load was 3,209 copies/mL using cdPCR. The average hospital stay of children with EBV infection (184 ± 91 days) was longer than that of children without EBV infection (125 ± 79 days), P = 0.026. CONCLUSION EBV cdPCR had good sensitivity and specificity. The incidence of EBV infection was 18.75% in 64 children after HSCT from May 2019 to September 2020. EBV cdPCR could therefore be a novel method to detect EBV viral load in children after HSCT.
Child ; DNA, Viral/analysis* ; Epstein-Barr Virus Infections/epidemiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Herpesvirus 4, Human/genetics* ; Humans ; Real-Time Polymerase Chain Reaction ; Viral Load