Safety and efficacy of linaclotide combined with polyethylene glycol for bowel preparation / 基础医学与临床

Objective To evaluate safety and efficacy of linaclotide combined with polyethylene glycol(PEG)for bowel preparation.Methods A total of 612 patients from Department of Gastroenterology at the Affiliated Hospital of Qingdao University for colonoscopy examination from January to June 2023 were selected.They were divided into group 1(1 L PEG+2 L PEG),group 2(linaclotide+2 L PEG)and group 3(1 L PEG+linaclotide+1 L PEG)by random number table method,with 204 cases in each group.The Ottawa Bowel Preparation Quality Scale(OBPS),the insertion time of colonoscopy,the time of the first defecation,the frequency of defecations,the occurrence of adverse effects and patients'tolerability were compared among the three groups.Results A total of 601 patients completed bowel preparation and accepted colonoscopy.Group 1 exhibited no statistically significant differences to group 2 with regards to OBPS and insertion time.However,Group 2 demonstrated a shorter duration for the time of the first defecation in comparison to both group 1 and group 3(P＜0.05).Group 1 displayed a higher frequency of defecations as compared to Group 2 and Group 3(P＜0.05).The incidence of adverse reactions was significantly lower in group 2 and group 3 than in group 1(P＜0.05).The overall tolerance score of patients in group 1 was low-er than that in group 2 and group 3(P＜0.05).Conclusions The effect of combining 2 L PEG with 290 μg of lina-clotide for bowel preparation before colonoscopy is similar to that of 3 L PEG.It can reduce the incidence of adverse reactions and patients exhibit good tolerance.For patients who are intolerant to a single high-dose administration of PEG,they need divided-dose regimen of 2 L PEG in combination with linaclotide.

Visualization analysis on implementation science in translation of clinical practice guidelines based on knowledge graph / 中国实用护理杂志

Objective:To investigate the hot topics and trends of implementation science in the transformation of clinical practice guidelines, in order to provide ideas and references for clinical managers to reasonably apply and implement scientific promotion guidelines.Methods:CiteSpace6.2.R3 software was used to visualize the literature, which retrieved from the core database of Web of Science, including the number of articles, countries and high-frequency keywords and keyword clustering and emergence for visual analysis, etc.Results:A total of 4 593 articles were included in the final analysis. Since 1993, the number of published papers had increased year by year. The hot topics focused on primary care, attitudes, knowledge translation, clinical trials, risk factors and machine learning. The research trends included older adults and artificial intelligence.Conclusions:The rapid development of implementation science in guideline translation research suggests that scholars from various countries, especially hospital administrators should reasonably apply implementation science framework to integrate evidence into clinical practice, and promote the implementation of clinical practice guidelines.

Development and progress in the application of smart health technologies for older adults with mild cognitive impairment / 中华老年医学杂志

Under the backdrop of smart health management technology development, this article reviews research advances in smart monitoring, assessment and intervention technologies for older people with mild cognitive impairment, including the types, typical applications and results of monitoring, assessment and intervention technologies.In addition, from the perspective of community-dwelling older adults' cognitive health management, a model for innovative management of community-dwelling older adults' cognitive function taking advantage of smart health management technologies is proposed, aiming to enhance the acceptance of smart health technologies among older people with cognitive impairment and to provide policy advice on developing friendly communities for older people with cognitive impairment.

Clinical analysis of 11 cases multisystem inflammatory syndrome associated with SARS-CoV-2 Omicron variant infection in children / 中华儿科杂志

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Propofol alleviates the disruption of blood-brain barrier caused by cerebral ischemia / 局解手术学杂志

Objective To investigate the protective effect and mechanism of propofol on the blood-brain barrier in rats with cerebral ischemia.Methods A total of 48 10-week-old male SD rats were randomly divided into the sham group,the cerebral ischemia group,the propofol group and the propofol+LY294002 group.Twenty-four hours before the induction of the model,the rats in the propofol+LY294002 group were intracerebroventricularly injected with PI3K inhibitor LY294002(0.3 mg·kg-1),and the rats in the other groups were administrated with saline(10 μL).Rats in the cerebral ischemia group,the propofol group and the propofol+LY294002 group established cerebral ischemia models by carotid artery occlusion.Rats in the sham group only isolated the common carotid artery and ligated the external carotid artery without other treatment.During the modeling period,the rats in the propofol group and the propofol+LY294002 group were given propofol(10 mg·kg-1)via the tail vein,and the sham group and the propofol group were treated with saline.After 24 hours,the neurological function of rats was evaluated by Zea Longa method;the area of cerebral infarction was detected by TTC staining;the degree of cerebral edema was detected by the dry-wet weight method.EB tracer method was used to evaluate the integrity of the blood-brain barrier;ELISA was used to detect inflammatory cytokines in cerebrospinal fluid;Western blot was used to detect the expression of PI3K/AKT signaling pathway proteins and blood-brain barrier tight junction proteins Claudin-5 and Occludin.Results Cerebral ischemia led to the increase of neurological function scores and local infarction of brain tissues in rats.Compared with the sham group,the EB content in the brain tissue of rats in the cerebral ischemia group increased,the degree of brain edema increased,and the content of inflammatory cytokines in the cerebrospinal fluid increased.And the use of propofol could significantly decrease the neurological function scores,reduce the area of cerebral infarction,inhibit EB penetrating blood-brain barrier,reduce the degree of brain edema,reduce the release of inflammatory cytokines,and up-regulate the expression of PI3K/AKT signaling pathway proteins and tight junction proteins Claudin-5 and Occludin.LY294002 significantly reversed the above effects of propofol.Conclusion Propofol can maintain the expression of tight junction proteins Claudin-5 and Occludin through the PI3K/AKT signaling pathway,protect the structural and functional integrity of blood-brain barrier,reduce the degree of brain edema,prevent other inflammatory cytokines into the brain tissue,reduce cerebral infarction,and alleviate the neurological functional damage caused by cerebral ischemia.

Study on cognitive load level and influencing factors of emergency nurses / 中国现代医生

Objective To explore the cognitive load level and influencing factors of emergency nurses.Methods Using convenience sampling method,48 nurses in emergency department of China-Japan Friendship Hospital from April to May 2022 were selected as research objects.General data were collected and total cognitive load and three different types of cognitive load were measured.Results Regression analysis showed that nurse-patient relationship was influencing factor of total cognitive load of nurses in emergency department(β=6.202,P=0.007),the noisy working environment was the influencing factor of the internal cognitive load(β=1.042,P<0.001),and the living situation(sharing with others)was the influencing factor of the external cognitive load(β=-3.917,P=0.006).The factors of associated with cognitive load were not found.Conclusion The total cognitive load and the three types of cognitive load of nurses in emergency department are high.Nursing managers can reduce the cognitive load of nurses in emergency department by adjusting related influencing factors,so as to improve nursing work efficiency.

Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-angiogenic activity of Kunxian Capsule (KX) extract and explore the underlying molecular mechanism using zebrafish.@*METHODS@#The KX extract was prepared with 5.0 g in 100 mL of 40% methanol followed by ultrasonication and freeze drying. Freeze dried KX extract of 10.00 mg was used as test stock solution. Triptolide and icariin, the key bioactive compounds of KX were analyzed using ultra-high performance liquid chromatography. The transgenic zebrafish Tg(flk1:GFP) embryos were dechorionated at 20-h post fertilization (hpf) and treated with PTK 787, and 3.5, 7, 14 and 21 µg/mL of KX extract, respectively. After 24-h post exposure (hpe), mortality and malformation (%), intersegmental vessels (ISV) formation, and mRNA expression level of angiogenic pathway genes including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinases (ERKs), mitogen-activated protein kinase (MAPK), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) were determined. Further, the embryos at 72 hpf were treated with KX extract to observe the development of sub-intestinal vein (SIV) after 24 hpe.@*RESULTS@#The chromatographic analysis of test stock solution of KX extract showed that triptolide and icariin was found as 0.089 mg/g and 48.74 mg/g, respectively, which met the requirements of the national drug standards. In zebrafish larvae experiment, KX extract significantly inhibited the ISV (P<0.01) and SIV formation (P<0.05). Besides, the mRNA expression analysis showed that KX extract could significantly suppress the expressions of PI3K and AKT, thereby inhibiting the mRNA levels of ERKs and MAPK. Moreover, the downstream signaling cascade affected the expression of VEGF and its receptors (VEGFR and VEGFR-2). FGF-2, a strong angiogenic factor, was also down-regulated by KX treatment in zebrafish larvae.@*CONCLUSION@#KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VEGF pathway and showed promising potential for RA treatment.

Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor / 中西医结合学报

OBJECTIVE@#This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR).@*METHODS@#Sprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway.@*RESULTS@#Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon.@*CONCLUSION@#Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation. Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194-204.

Influencing factors of corneal epithelial punctate staining in patients wearing orthokeratology / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the influencing factors of punctate staining of corneal epithelium in patients wearing orthokeratology.METHOD: Data of 280 cases wearing orthokeratology were collected, including 185 cases in the group without corneal staining and 95 cases in the group with corneal staining. All patients were examined for general distant vision, intraocular pressure, slit lamp, fundus examination after mydriasis, comprehensive optometry, corneal topography, corneal thickness, corneal endothelium, axial length, Schirmer Ⅰtest(SⅠt)before wearing lenses, meibomian gland loss score before wearing lenses, eccentric distance, interleukin-2(IL-2)in tear, tumor necrosis factor-α(TNF-α)content analysis and so on. The influencing factors of corneal epithelium punctate staining were analyzed by univariate and multivariate Logistic regression.RESULTS: There were significant differences in preoperative diopter, preoperative meibomian gland deletion score, IL-2, TNF-α and lens sediment between the two groups(all P&#x003C;0.05). Logistic regression analysis showed that diopter before wearing lenses was a protective factor for corneal epithelium punctate staining. Before wearing lenses, the loss of meibomian gland score, IL-2, TNF-α and lens deposits were the risk factors of corneal epithelium punctate staining. In the detection of corneal epithelium punctate staining, the comprehensive advantage of lens deposits was obvious, the specificity of lens deposits was higher, and the sensitivity of IL-2 was the highest. CONCLUSIONS: Before wearing lenses, diopter is the protective factor of corneal epithelium punctate staining, and the loss of meibomian gland score, IL-2, TNF-α and lens deposits are the risk factors of corneal epithelium punctate staining.

Genetic analysis of a child with Kartagener syndrome due to novel compound heterozygous variants of DNAH5 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic basis of a child with Kartagener syndrome (KTS).@*METHODS@#Trio-whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. Changes in protein structure due to missense variants were simulated and analyzed, and the Human Splicing Finder 3.0 (HSF 3.0) online platform was used to predict the effect of the variant of the non-coding region.@*RESULTS@#The child had featured bronchiectasis, sinusitis and visceral inversion. Genetic testing revealed that he has harbored compound heterozygous variants of the DNAH5 gene, namely c.5174T>C and c.7610-3T>G. Sanger sequencing confirmed the existence of the variants. The variants were not found in the dbSNP, 1000 Genomes, ExAC, ClinVar and HGMD databases. Protein structural analysis suggested that the c.5174T>C (p.Leu1725Pro) variant may affect the stability of local structure and its biological activity. The results of HSF 3.0 analysis suggested that the c.7610-3T>G variant has probably destroyed a splicing receptor to affect the transcription process.@*CONCLUSION@#The compound heterozygous variants of the DNAH5 gene probably underlay the pathogenesis in the child. Above finding may facilitate the understanding of the clinical characteristics and genetic basis of KTS, and further expand the spectrum of DNAH5 gene variants.

Anti-osteoporosis mechanism of Panax quiquefolium L. based on zebrafish model and metabonomics / 药学学报

In this study, we investigated the anti-osteoporotic activity and mechanism of action of extract of Panax quiquefolium L. based on zebrafish model combined with metabolomics technology. A zebrafish model of prednisolone-induced osteoporosis was used to compare the anti-osteoporotic activity of Panax quiquefolium L., and the expression of osteoblast-associated genes and osteoclast-associated genes in zebrafish was detected by quantitative real-time PCR (qRT-PCR), using bone fluorescence area and fluorescence density as evaluation indexes. Metabolomics based on ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to explore the change patterns of biomarkers and the metabolic pathways affected. The results showed that the 50% ethanol extracts of Panax quiquefolium L. from Jilin, Canada, Wenden and the United States can significantly improve the bone fluorescence area of zebrafish compared with model group. Furthermore, four sources 50% ethanol extracts of Panax quiquefolium L. except United States also can significantly improve the bone fluorescence density of zebrafish. In addition, PCR showed that extract of Panax quiquefolium L. can significantly up-regulated the expression of vitamin D receptor b (vdrb), collagen type I α2 (col1a2) and cysteine-rich acidic secreted protein (sparc) genes, and down-regulated the expression of matrix metalloproteinase 9 (mmp9), anti-tartrase acid phosphatase (trap) and cathepsin K (ctsk) genes. Metabolomic analysis identified 24 key differential metabolites. Furthermore, pathway analysis showed that Panax quiquefolium L. could regulate the levels of 10 key biomarkers by participating in purine metabolism, tricarboxylic acid cycle and pentose phosphate metabolism and improve the osteoporosis status of zebrafish. This study preliminically revealed the anti-osteoporosis mechanism of 50% ethanol extract from Panax quiquefolium L. through multi-component, multi-target and multi-pathway and also provides theoretical basis for clinical development and utilization of anti-osteoporosis products of Panax quiquefolium L. This experiment was approved by the Experimental Animal Welfare Ethics Committee of the Institute of Biology, Shandong Academy of Sciences (approval number: SWS20181002).

Current Status and Prospect of Orphan Drugs for Rare Skin Diseases in China / 罕见病研究

Rare diseases are characterized by extremely low incidence rate and small number of patients in total. The drugs used to treat rare diseases are called orphan drugs. Currently, 450 kinds of rare skin diseases have been identified, most of which lack in effective treatments. Supported by the policy-making from the country and pushed by all sectors of the society, drugs for rare skin diseases have been emerging continuously recently in China. This paper reviews the current accessibility of the orphan drugs for skin rare diseases that have been approved in China and in other countries and regions for a better understanding of rare dermatosis and orphan drugs for the diseases.

Effect evaluation of narrative medicine teaching in general practice residency training based on Mini-CEX / 中华全科医师杂志

Objective:To evaluate the effect of narrative medicine teaching in general practice residency training.Methods:Thirty-eight resident physicians who received standardized training in the Department of General Medicine in Shanghai Fifth People′s Hospital from November 2021 to November 2022 were randomly divided into trial group and control group with 19 individuals in each group. All residents received general medicine training according to the national standard curriculum, while narrative medicine was added to the teaching for the trial group. The teaching results were evaluated after 8 months of training. The indicators included mini-clinical evaluation exercise (Mini-CEX) assessment scores, academic assessment, narrative ability and empathy ability scores, self-assessment scores of learning effectiveness, and teaching satisfaction.Results:Among 38 residents, 15 were males and 23 were females with a mean age of (25.9±2.1) years. There were no significant differences in gender composition, age and education level of the two groups (all P>0.05). Mini-CEX results showed that the evaluation skills, physical examination, professionalism, clinical diagnosis, communication skills, organization and efficiency, and overall ability scores in the trial group were all significantly higher than those in the control group (all P<0.001). Examination results showed that there were no significant differences in knowledge test scores between the two groups ( P=0.208), however the skill manipulation performance in the trial group was significantly higher than that in the control group ( P=0.023). The narrative ability scores and empathy ability scores of the trial group were significantly higher than those in the control group (both P<0.001). In terms of learning effectiveness, the scores of stimulating interest in learning, scores of improving language expression ability, scores of learning good doctor-patient relationship, improving doctor-patient communication ability, and improving problem analysis ability in the trial group were significantly higher than those in the control group (all P<0.001). The teaching satisfaction rate of the trial group was 78.9% (15/19), which was higher than that of the control group (52.6%(10/19)). Conclusion:Adding narrative medicine teaching to the residency training can enhance the teaching effect of general practice residency training, especially in clinical practice ability, narrative ability and empathy ability.

Study of the effect of mid-ventricular obstruction on left ventricular systolic function in patients with hypertrophic cardiomyopathy by four-dimensional automatic left ventricular quantitation technology / 中华超声影像学杂志

Objective:To investigate the effect of mid-ventricular obstruction (MVO) on left ventricular systolic function in patients with hypertrophic cardiomyopathy(HCM) by four-dimensional automatic left ventricular quantitation technology(4D Auto LVQ).Methods:Fifty-seven hypertrophic obstructive cardiomyopathy patients were selected from December 2020 to October 2022 in the First Affiliated Hospital of Zhengzhou University. According to the presence of MVO, HCM patients were divided into two groups: HCM 1 group, HCM without MVO ( n=34); HCM 2 group, HCM with MVO ( n=23). In addition, 25 healthy subjects in the same period were selected as the control group. Conventional ultrasound parameters were collected, and 4D Auto LVQ technology was used to obtain the mechanical parameters of left ventricular myocardium, including left ventricular longitudinal strain (GLS), circumferential strain (GCS), area strain (GAS), radial strain (GRS), segmental longitudinal strain (SLS) and area strain (SAS). The differences of these parameters among the three groups were compared. Results:①Compared with the control group, the thickness of the maximum basal segment of interventricular septum, the thickness of the middle segment of the maximum interventricular septum, the thickness of the apical segment of the interventricular septum, the thickness of the left ventricular posterior wall and left atrium diameter were significantly increased. Six-minute walk distance and the left ventricular end-diastolic diameter was decreased in the two groups of HCM(all P<0.05). Left ventricular outflow tract gradients in HCM 1 group was higher than HCM 2 group( P<0.05), but there was no significant difference in left ventricular ejection fraction among the three groups( P>0.05). There was significant difference in the incidence of left ventricular apical aneurysm among the three groups( P<0.05). ②Compared with the control group, the GLS in both HCM groups was lower, and it was lower in the HCM 2 group than in the HCM 1 group(all P<0.05) the GRS and GAS in both HCM groups were lower than in the control group ( P<0.05), and there was no significant difference between the two groups of HCM, and there was no significant difference in GCS among the three groups(all P>0.05). ③Compared with the control group, the SLS of basal segment, middle segment, apical cap, posterior septum, inferior wall and lateral wall in HCM group were significantly lower than those in control group. The SLS of apical segment of posterior septum, anterior septum, anterior wall, posterior wall, inferior wall and apical segment of posterior septum, lateral wall and inferior wall in HCM 2 group were significantly lower than HCM 1 group(all P<0.05), but there was no significant difference in SLS of posterior septum, anterior septum, anterior wall, lateral wall and inferior wall between the two groups(all P>0.05). ④Compared with the control group, the SAS of posterior septal basal segment, middle segment, anterior septal middle segment, anterior wall basal segment, middle segment, apical segment, lateral wall basal segment, middle segment, apical segment, posterior wall basal segment, middle segment, inferior wall basal segment, middle segment and apical cap in HCM groups were significantly lower than the control group(all P<0.05), but there was no significant difference in SAS between the two groups of HCM( P>0.05). Conclusions:4D Auto LVQ can quantitatively evaluate the damage of MVO on the left ventricular systolic function in patients with HCM, especially for the evaluation of local myocardial function damage in the medial segment and apical segment.

Associations between serum GDF15 and glycolipid metabolism disorder in metabolic associated fatty liver patients / 中华内科杂志

Objective:To investigate relationships between serum growth differentiation factor 15 (GDF15) and glycolipid metabolism in patients with metabolic associated fatty liver disease (MAFLD).Methods:The current investigation was a cross-sectional study. A total of 333 patients from the Fengxian District Central Hospital were recruited into the study after physical examination from February 2020 to February 2021. There were 107 patients with MAFLD and type 2 diabetes mellitus (T2DM), including 54 males and 53 females with a mean age of (57±11) years. There were 65 patients with simple MAFLD only, including 32 men and 33 women with a mean age of (49±5) years. There were 105 patients with T2DM only, including 53 men and 52 women, with a mean age of (56±10) years. A control group of 56 people without MAFLD or diabetes,28 male, 28 female, mean age (48±6) years, was also included in the study. Serum GDF15 was measured via enzyme-linked immunosorbent assays. IBM SPSS 26.0 was used for statistical analysis. Logistic regression was used to evaluate relationships between GDF15 and metabolic abnormalities in MAFLD patients.Results:GDF15 progressively increased in the control [385 (296, 484) ng/L], nonobese MAFLD [388 (319, 435) ng/L], obese MAFLD [426 (354, 527) ng/L], T2DM [664 (483, 900) ng/L], and MAFLD+T2DM groups [770 (560, 1 074) ng/L]( H=113.82, P=0.001). There was no significant difference in serum GDF15 between the simple MAFLD [406 (339, 524) ng/L] and control group ( U=1 505.50, P=0.132). GDF15 was significantly higher in the MAFLD+T2DM group than in the T2DM-only group ( U=4 573.50, P=0.019). In logistic regression analysis increased GDF15 was associated with increased risks of simple MAFLD [odds ratio ( OR)=2.202], T2DM ( OR=29.656), and MAFLD+T2DM( OR=58.197). In patients with MAFLD, serum GDF15 was higher in the FIB4 index>1.45 group [773 (534, 1 162) ng/L] than in the FIB4 index<1.45 group [527 (389, 787) ng/L] ( U=1 709.50, P<0.001). Increased GDF15 was associated with an increased risk of advanced liver fibrosis ( OR=2.388). Conclusion:In patients with simple MAFLD, GDF15 level was not significantly higher than in the control group. In the T2DM-only group and the MAFLD+T2DM group GDF15 was significantly higher than in the control group. Increased serum GDF15 was associated with increased risk and severity of MAFLD complicated with abnormal glucose and lipid metabolism. High GDF15 increased the risk of advanced fibrosis in MAFLD patients.

Impact of VA-ECMO combined with IABP and timing on outcome of patients with acute myocardial infarction complicated with cardiogenic shock / 中华心血管病杂志

Objective: To investigate the impact of combined use and timing of arterial-venous extracorporeal membrane oxygenation (VA-ECMO) with intra-aortic balloon pump (IABP) on the prognosis of patients with acute myocardial infarction complicated with cardiogenic shock (AMICS). Methods: This was a prospective cohort study, patients with acute myocardial infarction and cardiogenic shock who received VA-ECMO support from the Heart Center of Lanzhou University First Hospital from March 2019 to March 2022 in the registration database of the Chinese Society for Extracorporeal Life Support were enrolled. According to combination with IABP and time point, patients were divided into VA-ECMO alone group, VA-ECMO+IABP concurrent group and VA-ECMO+IABP non-concurrent group. Data from 3 groups of patients were collected, including the demographic characteristics, risk factors, ECG and echocardiographic examination results, critical illness characteristics, coronary intervention results, VA-ECMO related parameters and complications were compared among the three groups. The primary clinical endpoint was all-cause death, and the safety indicators of mechanical circulatory support included a decrease in hemoglobin greater than 50 g/L, gastrointestinal bleeding, bacteremia, lower extremity ischemia, lower extremity thrombosis, acute kidney injury, pulmonary edema and stroke. Kaplan-Meier survival curves were used to analyze the survival outcomes of patients within 30 days of follow-up. Using VA-ECMO+IABP concurrent group as reference, multivariate Cox regression model was used to evaluate the effect of the combination of VA-ECMO+IABP at different time points on the prognosis of AMICS patients within 30 days. Results: The study included 68 AMICS patients who were supported by VA-ECMO, average age was (59.8±10.8) years, there were 12 female patients (17.6%), 19 cases were in VA-ECMO alone group, 34 cases in VA-ECMO+IABP concurrent group and 15 cases in VA-ECMO+IABP non-concurrent group. The success rate of ECMO weaning in the VA-ECMO+IABP concurrent group was significantly higher than that in the VA-ECMO alone group and the VA-ECMO+IABP non-concurrent group (all P<0.05). Compared with the ECMO+IABP non-concurrent group, the other two groups had shorter ECMO support time, lower rates of acute kidney injury complications (all P<0.05), and lower rates of pulmonary edema complications in the ECMO alone group (P<0.05). In-hospital survival rate was significantly higher in the VA-ECMO+IABP concurrent group (28 patients (82.4%)) than in the VA-ECMO alone group (9 patients) and VA-ECMO+IABP non-concurrent group (7 patients) (all P<0.05). The survival rate up to 30 days of follow-up was also significantly higher surviving patients within were in the ECMO+IABP concurrent group (26 cases) than in VA-ECMO alone group (9 patients) and VA-ECMO+IABP non-concurrent group (4 patients) (all P<0.05). Multivariate Cox regression analysis showed that compared with the concurrent use of VA-ECMO+IABP, the use of VA-ECMO alone and non-concurrent use of VA-ECMO+IABP were associated with increased 30-day mortality in AMICS patients (HR=2.801, P=0.036; HR=2.985, P=0.033, respectively). Conclusions: When VA-ECMO is indicated for AMICS patients, combined use with IABP at the same time can improve the ECMO weaning rate, in-hospital survival and survival at 30 days post discharge, and which does not increase additional complications.

Impact of VA-ECMO combined with IABP and timing on outcome of patients with acute myocardial infarction complicated with cardiogenic shock / 中华心血管病杂志

Objective: To investigate the impact of combined use and timing of arterial-venous extracorporeal membrane oxygenation (VA-ECMO) with intra-aortic balloon pump (IABP) on the prognosis of patients with acute myocardial infarction complicated with cardiogenic shock (AMICS). Methods: This was a prospective cohort study, patients with acute myocardial infarction and cardiogenic shock who received VA-ECMO support from the Heart Center of Lanzhou University First Hospital from March 2019 to March 2022 in the registration database of the Chinese Society for Extracorporeal Life Support were enrolled. According to combination with IABP and time point, patients were divided into VA-ECMO alone group, VA-ECMO+IABP concurrent group and VA-ECMO+IABP non-concurrent group. Data from 3 groups of patients were collected, including the demographic characteristics, risk factors, ECG and echocardiographic examination results, critical illness characteristics, coronary intervention results, VA-ECMO related parameters and complications were compared among the three groups. The primary clinical endpoint was all-cause death, and the safety indicators of mechanical circulatory support included a decrease in hemoglobin greater than 50 g/L, gastrointestinal bleeding, bacteremia, lower extremity ischemia, lower extremity thrombosis, acute kidney injury, pulmonary edema and stroke. Kaplan-Meier survival curves were used to analyze the survival outcomes of patients within 30 days of follow-up. Using VA-ECMO+IABP concurrent group as reference, multivariate Cox regression model was used to evaluate the effect of the combination of VA-ECMO+IABP at different time points on the prognosis of AMICS patients within 30 days. Results: The study included 68 AMICS patients who were supported by VA-ECMO, average age was (59.8±10.8) years, there were 12 female patients (17.6%), 19 cases were in VA-ECMO alone group, 34 cases in VA-ECMO+IABP concurrent group and 15 cases in VA-ECMO+IABP non-concurrent group. The success rate of ECMO weaning in the VA-ECMO+IABP concurrent group was significantly higher than that in the VA-ECMO alone group and the VA-ECMO+IABP non-concurrent group (all P<0.05). Compared with the ECMO+IABP non-concurrent group, the other two groups had shorter ECMO support time, lower rates of acute kidney injury complications (all P<0.05), and lower rates of pulmonary edema complications in the ECMO alone group (P<0.05). In-hospital survival rate was significantly higher in the VA-ECMO+IABP concurrent group (28 patients (82.4%)) than in the VA-ECMO alone group (9 patients) and VA-ECMO+IABP non-concurrent group (7 patients) (all P<0.05). The survival rate up to 30 days of follow-up was also significantly higher surviving patients within were in the ECMO+IABP concurrent group (26 cases) than in VA-ECMO alone group (9 patients) and VA-ECMO+IABP non-concurrent group (4 patients) (all P<0.05). Multivariate Cox regression analysis showed that compared with the concurrent use of VA-ECMO+IABP, the use of VA-ECMO alone and non-concurrent use of VA-ECMO+IABP were associated with increased 30-day mortality in AMICS patients (HR=2.801, P=0.036; HR=2.985, P=0.033, respectively). Conclusions: When VA-ECMO is indicated for AMICS patients, combined use with IABP at the same time can improve the ECMO weaning rate, in-hospital survival and survival at 30 days post discharge, and which does not increase additional complications.

A Family with Congenital Dysfibrinogenemia and Blood Transfusion / 中国实验血液学杂志

OBJECTIVE@#To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies.@*METHODS@#Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations.@*RESULTS@#The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery.@*CONCLUSION@#Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.

Aurora A Kinase Plays a Key Role in Mitosis Skip during Senescence Induced by Ionizing Radiation / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation (IR).@*METHODS@#Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237 (MLN) and/or p21 depletion by small interfering RNA (siRNA). Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator (FUCCI) system combined with histone H3 phosphorylation at Ser10 (pS10 H3) detection. Senescence was assessed using senescence-associated-β-galactosidase (SA-β-Gal), Ki67, and γH2AX staining. Protein expression levels were determined using western blotting.@*RESULTS@#Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment. The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells, ultimately leading to senescence in G1. During this process, the p53/p21 pathway is hyperactivated. Accompanying p21 accumulation, Aurora A kinase levels declined sharply. MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.@*CONCLUSION@#Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation, leading to senescence via mitotic skipping.

Selection and validation of reference genes for quantitative real-time PCR analysis in Paeonia veitchii / 中国中药杂志

Paeonia veitchii and P. lactiflora are both original plants of the famous Chinese medicinal drug Paeoniae Radix Rubra in the Chinese Pharmacopoeia. They have important medicinal value and great potential in the flower market. The selection of stable and reliable reference genes is a necessary prerequisite for molecular research on P. veitchii. In this study, two reference genes, Actin and GAPDH, were selected as candidate genes from the transcriptome data of P. veitchii. The expression levels of the two candidate genes in different tissues(phloem, xylem, stem, leaf, petiole, and ovary) and different growth stages(bud stage, flowering stage, and dormant stage) of P. veitchii were detected using real-time fluorescence quantitative technology(qRT-PCR). Then, the stability of the expression of the two reference genes was comprehensively analyzed using geNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that the expression patterns of Actin and GAPDH were stable in different tissues and growth stages of P. veitchii. Furthermore, the expression levels of eight genes(Pv-TPS01, Pv-TPS02, Pv-CYP01, Pv-CYP02, Pv-CYP03, Pv-BAHD01, Pv-UGT01, and Pv-UGT02) in different tissues were further detected based on the transcriptome data of P. veitchii. The results showed that when Actin and GAPDH were used as reference genes, the expression trends of the eight genes in different tissues of P. veitchii were consistent, validating the reliability of Actin and GAPDH as reference genes for P. veitchii. In conclusion, this study finds that Actin and GAPDH can be used as reference genes for studying gene expression levels in different tissues and growth stages of P. veitchii.