Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

Background::Sepsis is a serious disease caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis.Methods::We conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 h after intensive care unit (ICU) admission in two sites. All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days.Results::From September 27, 2018 to February 12, 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group ( P = 0.032). Cox regression showed that the aminophylline group had a lower hazard of death (hazard ratio = 0.312, 95% confidence interval: 0.129-0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time ( P = 0.039 by the log-rank test). The effects of aminophylline on vasopressor dose, oxygenation index, and sequential organ failure assessment score were time-dependent with treatment. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial. Conclusions::Aminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis.Trial registration::ChiCTR.org.cn, ChiCTR1800019173.

Animals ; Antigens, Surface/genetics* ; Cell Communication/genetics* ; Copulation/physiology* ; Fallopian Tubes/metabolism* ; Female ; Fertilization/genetics* ; GPI-Linked Proteins/genetics* ; Gene Expression Regulation ; Genes, Reporter ; Green Fluorescent Proteins/metabolism* ; Litter Size ; Luminescent Proteins/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism* ; Reproduction/genetics* ; Signal Transduction ; Sperm Count ; Sperm Motility/genetics* ; Spermatozoa/metabolism* ; Uterus/metabolism*

Objective To evaluate the efficacy and safety of terlipressin for septic shock.Methods A randomized double-blind placebo-controlled pilot study was carried out in the general ICU of the First Affiliated Hospital of Zhengzhou University from June 1st 2015 to May 31st 2016.The septic shock patients with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation were enrolled.Patients were randomized (random number) to give continuous infusions of either terlipressin[0.6-2.6 μg/(kg·h)] or norepinephrine(7-30 μg/min).Open label norepinephrine or other catecholamines were additionally infused if the mean arterial pressure failed to reach 65 mmHg.Treatment was continued until shock corrected,death or withdrawn from this study.Correcting rate of shock was the primary end point,the secondary end points included open labeled norepinephrine requirements,the 28 d survival rate and adverse events.The quantitative data of the two groups were compared by t test or Wilcoxon rank sum test.The enumeration data were compared by chi square test or Fisher exact probability method,and the survival data were analyzed by Kaplan-Meier method.Results A total of 28 patients were enrolled.The full analysis set was 28,the per-protocol set was 25,and the safety set was 28.The key demographics and baseline characteristics were similar between the two groups(P＞0.05).The results for the per-protocol set were followed up.The correcting rate of shock between the two groups were similar at the end of treatment[81.82％(9/11)vs.57.14％(8/14),P=0.190].The open label norepinephrine requirements of the trial group and control group for the 0,6,12,24,48 h time point were 0.661,0.921,1.583,1.241,2.143,1.371,1.071,1.261,0.370,1.001 μg/(kg·min),respectively with no significant difference(P＞0.05).The 28 d survival rate of the trial group and control group were 63.64％(7/11)and 50.00％(7/14) respectively with no statistical significance(P＞0.05).There was no significant difference in 28 d survival analyzed using Kaplan-Meier plot between two groups(P=0.470).There were two patients with ischemia of fingers,one patient with hyponatraemia and one patient with ischemia of intestine accompanied by hyponatraemia occurred after treatment with terlipressin,and one patient with isehemia of fingers occurred after treatment with norepinephrine.The incidence of adverse event for the trial group and control group were 30.77％(4/13) and 6.67％(1/15) with no significant difference(P=0.122).Conclusions Terlipressin is an effective agent for treating septic shock.The total adverse event rate of terlipressin was similar to that ofnorepinephrine.

Objective To analyze the efficacy and safety of nalbuphine in patients with sedative analgesia in intensive care unit (ICU). Methods A prospective observation was conducted. The adult patients with mild and moderate analgesia in general ICU of the First Affiliated Hospital of Zhengzhou University from January to November in 2017 were enrolled, and they were divided into nalbuphine group and sufentanil group in proper order. The nabobrown group was given 40 mg nabobrown, the sufentanil group was given 0.1 mg sufentanil, both of which were injected with 50 mL normal saline for continuous intravenous infusion in micro-pump. Infusion speed was checked according to pain level. The analgesic target was critical-care pain observation tool (CPOT) score < 2. The change in hemodynamics of patients in both groups were observed, and CPOT score and Richmond agitation-sedation scale (RASS) score were recorded before and l, 3, 5, 12, 24 hours after administration. The analgesic and sedative effects of two drugs were evaluated. Results A total of 141 patients were enrolled, including 71 patients in nalbuphine group and 70 in sufentanil group. There was no significant difference in general data including gender, age, body weight, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) or pain source, as well as baseline hemodynamics parameter between the two groups. At 1 hour and 3 hours after administration, nalbuphine had no effect on blood pressure, but the heart rate was decreased slightly, while the heart rate and blood pressure of the sufentanil group were decreased obviously. The two drugs could make the heart rate and blood pressure fluctuate obviously with the time of medication, but there was no statistical difference between the two drugs. The two drugs had no significant effect on pulse oxygen saturation (SpO2) during analgesia. The average dosage of nalbuphine was 0.03 (0.02, 0.05) mg·kg-1·h-1in the nalbuphine group, and the patient was satisfied with the analgesic effect until 3 hours after the use of the drug, and CPOT score was significantly decreased as compared with that before administration [1.0 (1.0, 2.0) vs. 3.0 (2.0, 4.0), P < 0.01], and the sedative effect was increased, RASS score was significantly lower than that before administration [0 (0, 1.0) vs. 1.0 (1.0, 2.0), P < 0.01]. No patients in naporphine group were treated with sufentanil due to unsatisfactory analgesia. The average dosage was 0.11 (0.06, 0.14) μg·kg-1·h-1in the sufentanil group, the patient was satisfied with the analgesic effect until 5 hours after administration, and the CPOT score was significantly lower than that before administration [1.0 (1.0, 2.0) vs. 4.0 (3.0, 6.0), P < 0.01], and the sedative effect was significantly increased, RASS score was significantly lower than that before administration [0 (-1.0, 0) vs. 2.0 (1.0, 2.0), P < 0.01]. The scores of CPOT and RASS in the sufentanil group were significantly higher than those of the naporphine group before use, so the decrease in the CPOT and RASS scores of the two drugs was further analyzed, which indicated the decrease in CPOT score of naporphine group was significantly lower than that in sufentanil group from 3 hours on [1.0 (0, 2.0) vs. 2.0 (1.0, 3.0), P < 0.05], and the decrease in RASS score of naporphine group was significantly lower than that in sufentanil group from 1 hour on [0 (0, 1.0) vs. 1.0 (0, 2.0), P < 0.01]. It suggested that naporphine could achieve sustained and stable analgesic effect and avoid excessive sedation caused by sufentanil. Conclusions Naporphine had a sustained and stable analgesic effect on patients with mild and moderate ICU analgesia. The onset time of naporphine was equivalent to sufentanil, and it had a certain sedative effect and less influence on hemodynamics.

BACKGROUND:Rehabilitation outcomes of patients with spinal cord injury are associated with degree of injury, therapeutic method, recovery time and subsequent treatment. Multidisciplinary, comprehensive, specialized rehabilitation unit can provide a better recovery after spinal cord injury. OBJECTIVE:To review the effect or combined effect of rehabilitation units after spinal cord injury. METHODS:A computer-based search of Springer and PubMed databases was done using the keywords of“spinal cord injury, rehabilitation practice, outcomes”, which appeared in the title and abstract. Final y, 44 English papers were included in result analysis. RESULTS AND CONCLUSION:Based on practical evidence, various rehabilitation practices are recognized, and then, the relevant information is connected with the outcomes to evaluate the efficacy of rehabilitation interventions. Studies have shown that age had no influence on rehabilitation outcomes in traumatic and non-traumatic mixed samples, and there is also little difference in the rehabilitation outcomes between male and female. Incidence of complications is lowest in the vast majority of patients with spinal cord injury who are initial y admitted to a specialist center of spinal cord injury. The hospital stay can be shorten in patients who can be admitted to a multidisciplinary, comprehensive, specialized division of spinal cord injury as early as possible. Patients who can receive regular, comprehensive outpatient fol ow-up show no significant differences in health perception, independence and depression, but the frequency and degree of certain secondary situations can be significantly reduced.

BACKGROUND:Ti6Al4V is a titanium aloy that is widely used in human joint replacement, but its modulus of elasticity is greater than human bone, resulting in the bad stability of the prosthesis. Ti35Nb3Zr2Ta, a new βtitanium aloy, has a lower modulus of elasticity, and maybe becomes a new-generation human joint prosthesis material that has a better biocompatibility. OBJECTIVE:To study the biocompatibility of Ti35Nb3Zr2Ta in prosthesis. METHODS:Wanfang, CNKI and PubMed databases were retrieved using a computer with “new β titanium;prosthesis; biocompatible” as keywords, and the retrieval time ranged from 2010 to 2015. Articles focusing on current application status for medical prosthesis materials and the biocompatibility of Ti35Nb3Zr2Ta in prosthesis were selected. RESULTS AND CONCLUSION:Compared with Ti6Al4V, Ti35Nb3Zr2Ta has higher surface roughness and smaler surface contact angle; the alkaline phosphatase activity and amount of calcium deposits in osteoblasts cultured at Ti35Nb3Zr2Ta is significantly higher than that at Ti6Al4V. Ti35Nb3Zr2Ta has good biocompatibility, and can be considered to be widely used as joint prosthesis material further.

AIM:To investigate the effect of Notch-1 knockdown on the growth of dihydroartemisinin-inhibited human osteosarcoma cell line U-2OS.METHODS:U-2OS cells treated with different concentrations of dihydroartemisinin (5, 10, 15 and 20μmol/L) were collected.The expression of Notch-1, MMP-2, MMP-9 and Hes-1 at mRNA and protein levels was measured by real-time PCR and Western blotting, respectively.U-2OS cells were transfected with Notch-1 siRNA for 24 h and incubated with dihydroartemisinin for another 24 h.The cell apoptotic rate , protein expression of MMP-2, MMP-9 and Hes-1, and the migration ability were measured by MTT assay , Western blotting and Transwell experiment , respectively.RESULTS:Dihydroartemisinin (5, 10, 15 and 20 μmol/L) decreased the expression of Notch-1, MMP-2, MMP-9 and Hes-1 at mRNA and protein levels in a dose-dependent manner .Down-regulation of Notch-1 significantly en-hanced the effect of dihydroartemisinin on the cell apoptosis , the protein expression of MMP-2, MMP-9 and Hes-1, and mi-gration ability ( P<0.05 ) .CONCLUSION: Notch-1 pathway is involved in the process of dihydroartemisinin-inhibited U-2OS cell growth.Knockdown of Notch-1 augments the inhibitory effect of dihydroartemisinin on U-2OS cell viability.

BACKGROUND:Previous experiments have prepared shape memory polymer based on D,L-poly(lactic acid). According to domestic technical requirements for biological y evaluating biomaterials and medical equipments, tissue-engineered grafts must be subjected to preclinical experiment for biosecurity and cytocompatibility evaluation.
OBJECTIVE:To observe the biosecurity of the shape memory polymer based on D,L-poly(lactic acid).
METHODS:(1) Bacterial endotoxin test:polymer extract, endotoxin working standard solution and checking
standard water were added into limulus reagent, respectively. (2) Sensitization test:Polymer extract+Freund’s complete adjuvant+physiological saline and Freund’s complete adjuvant+physiological saline were injected into the scapula of Kunming mice. After induction by intradermal injection, local induction and excitation, stimulate skin erythema and edema degree were observed in animals. (3) Acute toxicity test:Kunming mice received intraperitoneal injection of 100%, 50%, 25%polymer leaching solution and physiological saline, respectively. (4) 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay for cel proliferation:The direct method was that human umbilical cord vascular endothelial cel s were inoculated onto the polymer film, lactic acid and glass, respectively;the indirect method was that human umbilical cord vascular endothelial cel s were inoculated into the polymer leaching solution, acrylamide solution and 1640 culture solution.
RESULTS AND CONCLUSION:This shape memory polymer based on D,L-poly(lactic acid) is free of bacterial contamination in compliance with the biosecurity standards, and it has no al ergenic and toxicity but has good cytocompatibility.

UNLABELLEDA new kind of Interbody Cage made of multi-amino acid copolymer/tri-calcium phosphate (MAACP/TCP) composite was designed, and the purpose of this study was to evaluate immediate stability of MAACP/TCP Cage in a goat cervical spine model (C3-4). After the motion segment C3-4 was tested intact, 27 goat cervical spines were divided into three groups randomly. There were four groups group A. MAACP/TCP Cage group (n = 9), group B2 titanium Cage group (n = 9), group C2 autologous tricortical iliac crest bone group (n = 9) and group D: intact group (n = 27). Different Cage groups were implanted after complete discectomy (C3-4) was performed. Then they were tested in flexion, extension, axial rotation, and lateral bending with a nondestructive stiffness method. The range of motion (ROM) and relative stiffness were calculated and compared between groups. In comparison to the intact motion segment, MAACP/TCP Cage showed a significantly (P < 0.05) lower ROM and a significantly (P < 0.05) higher relative stiffness in flexion and lateral bending. In comparison to the tricortical iliac crest bone graft, MAACP/TCP Cage showed a significantly (P < 0.05) lower ROM and a significantly (P < 0.05) higher relative stiffness in extension, flexion and lateral bending. There was no significant (P > 0.05) difference in the ROM and relative stiffness between MAACP/TCP Cage and titanium Cage in extension, flexion and lateral bending. In comparison to titanium Cage, MAACP/TCP Cage showed a significantly (P < 0.05) higher ROM and a significantly (P < 0.05) lower relative stiffness in rotation.

CONCLUSIONMAACP/TCP Cage can provide enough immediate stability for cervical interbody fusion in a goat cervical spine model.

Absorbable Implants ; Amino Acids ; chemistry ; Animals ; Biomechanical Phenomena ; Calcium Phosphates ; chemistry ; Cervical Vertebrae ; surgery ; Evaluation Studies as Topic ; Female ; Goats ; Implants, Experimental ; Polymers ; chemistry ; Spinal Fusion ; instrumentation