Objective To investigate the protective effect of herba artemisiae scopariae extract on multidrug resistance protein 3(MDR3)gene mutation-induced neonatal parenteral nutrition-associated cholestasis(PNAC)and its possible mechanism.Methods ①Human primary hepatocytes were treated with cell culture in vitro,CRISPR/Cas9 lentivirus infection and MDR3 mutant gene lead-in.The levels of hepatic and biliary biochemical indexes[alanine transaminase(ALT),aspartate transaminase(AST),total bilirubin(TBil),direct bilirubin(DBil),indirect bilirubin(IBil),total bile acid(TBA)]in the supernatant of hepatocytes before and after 16,32,48 hours were compared to determine the time required for fatty acid induction of PNAC hepatocyte model with MDR3 gene mutation.② Human primary hepatocytes were divided into blank control group,MDR3 gene wild type group,MDR3 gene mutation group,and herba artemisiae scopariae extract intervention group according to random number table method.The blank control group was treated with culture medium only,the MDR3 gene wild type group was infected with lentivirus and mixed with wild type MDR3 gene and culture medium,the MDR3 gene mutation group was infected with lentivirus and cultured in culture medium with the mutant genes lead-in of LV-MDR3KI(c.485T>A,c.2793insA,c.1031G>A,c.3347G>A)mutation,while the MDR3 mutant gene was lead-in by lentivirus infection and cultured in culture medium,and then pretreated with 100 g/L herba artemisiae scopariae extract in the herba artemisiae scopariae extract intervention group,then the four groups of hepatocytes were induced with 1%fat emulsion,and the treatment time was the time needed to construct the PNAC hepatocytes model with MDR3 gene mutation.The levels of ALT,AST,TBil,DBil,IBil and TBA in the supernatant of hepatocytes were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA expression abundance of adenosine triphosphate binding cassette proteins(ABCB4,ABCB11,ABCC2,ABCC3,ABCC4)encoding MDR3,bile salt export pump(BSEP),multidrug resistance associated protein(MRP)2-4,and tumor necrosis factor-α(TNF-α)genes were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results Compared to the blank control group and MDR3 gene wild type group,there was no significant difference in the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 gene mutant group before and 16 hours after induction with 1%fat emulsion,however after treated with 1%fat emulsion for 32 hours and 48 hours,the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 mutant hepatocytes were significantly increased(P<0.05),consequently the time required for fatty acid induction of PNAC hepatocyte model was 32 hours.At 32 hours after treatment with fat emulsion,the levels of ALT,AST,TBil,DBil,TBA in the supernatant of hepatocytes in the herba artemisiae scopariae extract intervention group were significantly decreased[ALT(ng/L):148.3±2.3 vs.164.9±7.0,AST(ng/L):2767.4±78.8 vs.3239.4±107.1,TBil(μmol/L):7.6±0.2 vs.13.6±0.3,DBil(μmol/L):1.8±0.1 vs.5.7±0.2,TBA(μmol/L):3.4±0.2 vs.6.7±0.1,all P<0.05].The ABCB4,ABCC2,ABCC3,ABCC4 mRNA expression of MDR3,MRP2,MRP3,MRP4 in the blank control group,MDR3 wild type group,MDR3 gene mutation group and the herba artemisiae scopariae extract intervention group had no significant difference.The expression of TNF gene mRNA was highly expressed in MDR3 gene mutation group(2-??Ct:1.258±0.200 vs.1.001±0.052),and was low expressed in the herba artemisiae scopariae extract intervention group(2-??Ct:0.387±0.247 vs.1.258±0.200),and there was a significant difference between the two groups(both P<0.05).Compared to the MDR3 gene mutation group,the ABCB11 gene encoding BSEP mRNA expression in the herba artemisiae scopariae extract intervention group was significantly increased(2-??Ct:2.955±0.479 vs.1.333±0.529,P<0.05).Conclusion The herba artemisiae scopariae extract has a protective effect on PNAC induced by MDR3 gene mutation,which may be related to antagonizing inflammatory reaction,decreasing the expression of TNF mRNA and improving the expression of ABCB11 gene encoding BSEP.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective Based on the comparison and analysis of Raman spectra of liver meridian(including other meridian)and non-liver meridian(other meridian excluding liver meridian)traditional Chinese medicine,the accurate quantitative characterization data of liver meridian was obtained,and the liver meridian identification model was established and analyzed.Methods Taking 120 non-liver meridian(other meridian excluding liver meridian)traditional Chinese medicines(TCMs)as blank control and 120 liver-meridian(including other meridian)TCMs as experimental medicines,Raman spectra of 240 TCMs were obtained after sample pretreatment and Raman spectroscopy detection,and then quantified in units of 1 cm-1.Then combined with Random Forest(Random Forest,RF),Artificial Neural Network(Artificial Neural Network,ANN)and other algorithms,we constructed the identification models of quantized characterization of liver meridian.Results Compared with non-liver meridian(other meridian excluding liver meridian)TCMs,the Raman spectra of the liver meridian TCM were generally lower in the whole detection range,especially in the range of 200-1100 cm-1.The quantized Raman spectrogram data combined with ANN presented the best discrimination results with accuracy,precision>0.871,the receiver operating characteristic curve(ROC)was drawn and the area under ROC curve(AUC)was obtained,with AUC>0.921.Conclusion The Raman spectrogram of TCMs has significant correlation with liver meridian,which can be used as a whole quantized characterization of liver meridian.Combined with ANN,Raman spectrogram can carry out identification analysis efficiently and accurately,which is conducive to solving the bottleneck problem of lacking accurate data on medicinal properties and enriching the scientific connotation of attributing meridians.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients. METHODS: A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality. RESULTS: The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1. CONCLUSIONS Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Humans ; Middle Aged ; Young Adult ; Genotype ; Neutrophils ; Plasminogen Activator Inhibitor 1/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Retrospective Studies ; Sepsis/genetics*

Background: The incidence of inflammatory bowel disease (IBD) is increasing yearly, some of the IBD patients have extraintestinal manifestations (EIM), and EIM has impact on the treatment of IBD. Aims: To summarize the clinical characteristics of IBD patients associated with EIM, and evaluate the therapeutic effect of infliximab (IFX). Methods: The clinical data of IBD patients associated with EIM from January 2010 to December 2020 at the First Affiliated Hospital of Dalian Medical University were retrospectively analyzed, and the therapeutic effect of IFX was investigated. Results: In 811 patients with IBD, 50 (6.17%) patients had EIM. The commonly seen EIM was arthritis (78.00%) and erythema nodosum (26.00%); 52.00% had one EIM; 68.42% of UC patients with EIM involved E3, and 50.00% of CD patients with EIM involved L3. A total of 21 patients received IFX treatment, 2 weeks after medication, HB and ALB significantly increased, while ESR, CRP and PLT significantly decreased. Twenty⁃two weeks after medication, 83.33% of UC patients turned mild, and 70.00% of CD patients entered the remission phase. After the use of IFX, the first disappearance time of arthritis was significantly decreased when compared with those without using IFX (2.50 days vs. 10.50 days, P<0.05). The median time for the first disappearance of arthritis in patients with elevated CRP was significantly decreased than in patients with normal CRP (3.00 days vs. 9.00 days, P<0.05). Conclusions: Arthritis and erythema nodosum are common EMI in patients with IBD, and the treatment with IFX can significantly shorten the time of the first disappearance of some EIM.

In this study, the effects of two plant growth-promoting bacteria Klebsiella michiganensis TS8 and Lelliottia Jeotgali MR2 on the growth and cadmium (Cd) uptake of Arabidopsis thaliana under Cd stress were explored. A wild-type Arabidopsis thaliana was selected as the experimental plant and was planted at different Cd concentrations. MR2 and TS8 bacterial suspensions were sprayed onto the rhizospheric soil during the planting process. The initial Cd concentration of the bought soil was 14.17 mg/kg, which was used as the pot soil of the low-concentration Cd treatment group (LC). The concentration of soil Cd at high-concentration Cd treatment group (HC) were 200 mg/kg higher than that at LC group. Compared with the control group, MR2 suspension significantly promoted the growth of A. thaliana at both low and high concentrations, while TS8 strain and MR2_TS8 mixture only exhibited growth-promoting effect at high concentration. However, it was noteworthy that, TS8 suspension significantly reduced the Cd content in the underground parts of A. thaliana (60% and 59%), and significantly improved the Cd content in the aboveground parts of A. thaliana (234% and 35%) at both low and high concentrations. In addition, at low concentration, both single strain and mixed strains significantly improved the transformation from reducible Cd to acid-extractable Cd in soil, promoted Cd intake, and thereby reduced the total Cd content in soil. Therefore, the rational application of plant growth-promoting bacteria may improve crop yield and remediate Cd contamination in soil.
Arabidopsis ; Bacteria ; Biodegradation, Environmental ; Cadmium/pharmacology* ; Enterobacteriaceae ; Klebsiella ; Plant Roots/chemistry* ; Soil ; Soil Pollutants

Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.

Objective To explore efficacy and safety of simulated artificial pancreas in modulating stress hyperglycemia in critically ill patients. Methods A prospective randomized controlled study was performed. Seventy-two critically ill patients with stress hyperglycemia, aged 18-85 years, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score over 15, two consecutive random blood glucose 11.1 mmol/L or higher, glycated hemoglobin (HbA1C) below 0.065, unable to eat food for 3 days after inclusion, or only accepting parenteral nutrition, admitted to intensive care unit (ICU) in Shanghai Punan Hospital of Pudong New District from January 1st, 2015 to June 30th, 2017 were enrolled. The patients were divided into three groups according to the random number table method, high-intensity group and low-intensity group were injected Novolin R (high-intensity group 2/3 dosage, low-intensity group 1/3 dosage) to modulate stress hyperglycemia by simulated artificial pancreas. Simulated artificial pancreas consisted of Guardian real time glucose monitoring system (GRT system), close-circle control algorithm and micro-pump;subcutaneous injection of Humulin 70/30 was applied to modulate stress hyperglycemia in humulin group. Real-time glucose levels of interstitial fluid in abdominal wall, equivalent to blood glucose levels, 10 minutes each time, were monitored by using of GRT system for all patients in three groups. Fasting serum levels of stress hormones including epinephrine and cortisol and insulin resistance index (IRI) were recorded within 24 hours after inclusion. Mean blood glucose, blood glucose variation coefficient, blood glucose target-reaching rate, blood glucose target-reaching time, hypoglycemia rate and 6-month mortality were measured. Twenty healthy adults from health administration department of the hospital were recruited as healthy control group. Results A total of 60 eligible critically ill patients were included in this study, each group with 20 patients. There was no significant difference in gender, age, APACHE Ⅱ scores among three groups. The levels of serum epinephrine, cortisol and IRI within 24 hours after inclusion in the three groups were significantly higher than those in healthy control group. The mean blood glucose levels of humulin group, low-intensity group, high-intensity group were decreased (mmol/L: 10.2±3.2, 8.4±2.6, 8.1±2.2), the blood glucose target-reaching rate were increased [40.2% (3 295/8 196), 71.1% (5 393/7 585), 80.4% (6 286/7 818)], the blood glucose target-reaching time were shortened (hours: 49.1±5.8, 24.6±4.6, 17.5±4.2), the hypoglycemia rates were increased respectively [1.3% (108/8 196), 2.8% (211/7 585), 4.0% (313/7 818)], with statistically significant differences (all 1 = 0.000). There was no significant difference in blood glucose variation coefficient and 6-month mortality among three groups [blood glucose variation coefficient: (29.4±3.7)%, (28.5±5.3)%, (26.1±4.6)%, 6-month mortality: 55.0%, 45.0%, 40.0%, all 1 > 0.05]. Conclusions Simulated artificial pancreas could effectively and safely modulate stress hyperglycemia in critically ill patients, high-intensity modulation could bring about better efficacy in the regulation of hyperglycemia. High-frequency blood glucose monitoring by using GRT system could promptly identify hypoglycemia and help it to be corrected.

Objective To explore the effect of modified Seldinger technology in PICC intubation for chemotherapy . Methods Forty patients with chemotherapy during January to December 2014 were assigned as the control group, where the traditional PICC intubation was used, and another forty patients during January to December 2014 as the observation group, where modified Seldinger technology was used. The two groups were compared in terms of post-intubation comfort, puncture success rate, bleeding rate and complications. Results The post-intubation comfort degree of the observational group was significantly higher than that of the control group (P<0.05). The total puncture success rate and one-time success rate were both statistically significantly higher than those of the control group, and the rates of obstruction and infection were significantly lower than those of the control one (P<0.05). Conclusion Modified Seldinger technology used for intubation for chemotherapy can help improve comfort degree and safety and reduce the rate of complications.

Objective To evaluate the feasibility of T2 *mapping T2 *value combined with DWI ADC value in quantitative assessment of the activity of sacroiliitis.Methods 30 patients diagnosed with ankylosing spondylitis (AS)were divided into 2 groups as acute group (n=17)and chronic group (n=13)according to the BASDAI scores of the clinical severity of disease.And 20 healthy adults were recruited as control group.All groups were examined by MR with traditional sequence,T2 *mapping and DWI in the sacroiliac joint.The T2 *value and ADC value of the bone marrow edema region and normal region were measured.Furthermore,the imaging data and the clinical scores were statistical analysis and compared among three groups.Results T2 *values and ADC values in acute group of AS patients were higher than chronic group (P<0.05),as well as compared with healthy volunteers (P<0.05).There was no statistically significant difference between the chronic group of AS patients and control group (P>0.05).Positive correlation between ADC value and BASDAI was observed in patients group.Conclusion T2 *mapping combined with DWI imaging in AS is beneficial for early diagnosis and quantitative analysis of the activity of sacroiliitis.