ICU-acquired weakness (ICU-AW) is a common complication in the intensive care unit (ICU). The occurrence of ICU-AW directly leads to prolonged ICU stays for critically ill patients, and in severe cases, it continues to affect their quality of life even after discharge. This article provides a comprehensive review of the research progress on ICU-AW based on domestic and foreign studies, aiming to provide a scientific overview of ICU-AW, including its definition, pathophysiology, diagnosis, screening tools, influencing factors, and potential intervention strategies, so as to promote timely planning and implementation of relevant screening and intervention measures.

Objective To investigate the effects of allergens on the expressions of IL-18,IL-18BPa and IL-18Rα protein in peripheral blood CD4+Th1 cells of healthy control subjects(HC)and patients with allergic rhi-nitis(AR),and on the expressions of IL-18,IL-18BPa and IL-18Rα mRNA in the peripheral blood CD4+T cells.Methods Blood samples were collected from patients with rhinitis for negative skin prick test(AR-),rhinitis for positive skin prick test(AR+)and HC.Flow cytometry was used to evaluate the effects of allergens on the expres-sions of IL-18,IL-18BPa and IL-18Rα protein in CD4+Th1 cells.The expressions of IL-18,IL-18BPa and IL-18Rα mRNA in CD4+T cells were determined by qPCR.Results Compared with HC,increased IL-18 while de-creased IL-18BPa expressions in Th1 cells of AR-and AR+patients were observed,increased IL-18Rα expression in Th1 cells of AR+patients was also found.Additionally,allergens induced elevated expression of IL-18Rα pro-tein in Th1 cells of HC,and induced elevated mRNA expressions of IL-18,IL-18BPa and IL-18Rα in isolated blood CD4+T cells of AR+patients and HC.Conclusion Allergens may be involved in the pathogenesis of AR by inducing the expressions of IL-18 and IL-18Rα in blood CD4+Th1 cells.

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 To explore the role of sulodexide(SDX)in neointimal hyperplasia of arteriovenous fistulas(AVFs)in chronic kidney disease(CKD)rats and its possible mechanism.Methods A total of 18 male rats(weighing 300±50 g)were randomly and equally divided into AVF group,CKD+AVF group(CKD induction followed by AVF surgery and then gavaged with normal saline for 2 months),and CKD+AVF+SDX group[treated as in the CKD+AVF group but with 8 mg/(kg·d)SDX gavage].HE staining was used to observe the degree of neointimal hyperplasia.The expression of Hippo pathway related molecules,Yes-associated protein(YAP),pYAP and connective tissue growth factor(CTGF,YAP downstream target protein,one of mesenchymal marker)was detected by immunofluorescence assay.After human umbilical vein cell fusion EAHy926 cells were treated with 0,2.5,5,10,20 or 40 μg/mL SDX for 24 h,and with 2.5 μg/mL SDXfor24,48 or 72 h,respectively,CCK-8 assay was used to measure cell survival rate.Moreover,the serum sample from CKD rat was used to treat EAHy926 cells,and then the cells were treated with SDX or YAP inhibitor verteporfin.The expression levels of YAP,pYAP,CTGF and endothelial cell marker CD31 were detected by Western blotting.Results HE staining and immunofluorescence assay showed that CKD rats had serious neointimal hyperplasia in AVFs(P＜0.05),and slightly lower expression of pYAP and enhanced expression of CTGF(P＜0.05)when compared with the rats of the AVF group.While,SDX treatment alleviated the neointimal hyperplasia of AVFs,enhanced the expression of pYAP and reduced the expression of CTGF(P＜0.05).CCK-8 assay showed that cell survival rate was decreased significantly in a dose-and time-dependent manner after SDX treatment(P＜0.05).Western blotting revealed that SDX increased the expression of pYAP and CD31 while inhibited the expression of CTGF in EAHy926 cells(P＜0.05),which was consistent with the effect of verteporfin treatment.Conclusion SDX can block YAP activation caused by CKD and attenuate neointimal hyperplasia in AVFs.

OBJECTIVE: To explore the genetic etiology for a child with profound intellectual disabilities and obvious behavioral abnormalities. METHODS: A male child who had presented at the Zhongnan Hospital of Wuhan University on December 2, 2020 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Short tandem repeat (STR) analysis was carried out to determine its parental origin. The splicing variant was also validated in vitro with a minigene assay. RESULTS: WES results revealed that the child had harbored a novel splicing variant of c.176-2A>G in the PAK3 gene, which was inherited from his mother. The results of minigene assay have confirmed aberrant splicing of exon 2. According to the guidelines from the American College of Medical Genetics and Genomics, it was classified as a pathogenic variant (PVS1+PM2_Supporting+PP3). CONCLUSION The novel splicing variant c.176-2A>G of the PAK3 gene probably underlay the disorder in this child. Above finding has expanded the variation spectrum of the PAK3 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.
Child ; Female ; Humans ; Male ; Pregnancy ; Exons ; Intellectual Disability/genetics* ; Mothers ; Mutation ; p21-Activated Kinases/genetics* ; Parents ; RNA Splicing

Objective:To evaluate the role of G-rich RNA sequence binding factor 1 (GRSF1) in cerebral ischemia-reperfusion (I/R) injury in mice and the relationship with ferroptosis.Methods:Twenty-four clean-grade male C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (Sham group), cerebral I/R group (IR group), cerebral I/R+ GRSF1 overexpression group (IR+ LV-GRSF1 group), and cerebral I/R+ GRSF1 overexpression+ glutathione peroxidase 4 (GPX4) inhibitor group (IR+ LV-GRSF1+ RSL3 group). The model of middle cerebral artery occlusion was developed by thread-occlusion method in anesthetized animals. In IR+ LV-GRSF1 group, GRSF1-overexpressed lentivirus 2 μl was injected into the lateral ventricle at 7 days before the development of the model. GPX4 inhibitor RSL3 5 mg/kg was intraperitoneally injected for 2 consecutive days before the development of the model in IR+ LV-GRSF1+ RSL3 group. After 24 h of reperfusion, the percentage of cerebral infarction volume was determined by TTC assay, the survival neurons in ischemic area were detected by Nissl staining, and brain tissues in ischemic area were obtained for determination of the expression of p16, p21(markers of senescence) and tumor necrosis factor-alpha (TNF-α, senescence-associated secretory phenotype) mRNA (by quantitative real-time polymerase chain reaction), contents of malondialdehyde (MDA), superoxide dismutase(SOD) and glutathione (GSH) (by enzyme-linked immunosorbent assay) and expression of GRSF1, GPX4, Acyl-CoA synthetase long-chain family member 4 (ACSL4) and ferritin (by Western blot). Results:Compared with Sham group, the percentage of cerebral infarction volume was significantly increased, the count of viable neurons was decreased, the expression of p16, p21 and TNF-α mRNA in ischemic brain tissues was up-regulated, SOD and GSH contents were decreased, the MDA content was increased, the expression of GRSF1 and GPX4 was down-regulated, and the expression of ACSL4 and ferritin was up-regulated in IR group ( P<0.05). Compared with IR group, the percentage of cerebral infarction volume was significantly decreased, the count of viable neurons was increased, the expression of p16, p21 and TNF-α mRNA in ischemic brain tissues was down-regulated, SOD and GSH contents were increased, the MDA content was decreased, the expression of GRSF1 and GPX4 was up-regulated, and the expression of ACSL4 and ferritin was down-regulated in IR+ LV-GRSF1 group ( P<0.05). Compared with IR+ LV-GRSF1 group, the percentage of cerebral infarction volume was significantly increased, the count of viable neurons was decreased, the expression of p16, p21 and TNF-α mRNA in ischemic brain tissues was up-regulated, SOD and GSH contents were decreased, the MDA content was increased, the expression of GRSF1 and GPX4 was down-regulated, and the expression of ACSL4 and ferritin was up-regulated in IR+ LV-GRSF1+ RSL3 group ( P<0.05). Conclusions:GRSF1 is involved in the endogenous protective mechanism against cerebral I/R injury by up-regulating GPX4 expression, attenuating oxidative stress, and thus inhibiting ferroptosis in mice.

Objective:To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate.Methods:Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups.Results:A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. ① There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE Ⅱ: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [μmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. ② Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). ③ Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. ④ Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. Conclusions:CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

Objective:To study the intervention effect of ganoderma triterpenoids combined with exogenous monosialotetrahexosyl ganglioside(GM1) on cognitive dysfunction and synaptic ultrastructure of hippocampal neurons in rats with epilepsy caused by pentylenetetrazol(PTZ).Methods:A total of 40 Sprague-Dawley rats were divided into blank control group, epileptic model group, ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group according to the random number table method( n=8 in each group). The rats were intraperitoneally injected with PTZ subconvulsant dose (35 mg·kg -1·d -1) once a day for 28 days to replicate the models of chronic epilepsy. And the rats in different medication groups were given corresponding administration based on daily intraperitoneal injection of PTZ(GM1: intraperitoneal injection of 30 mg·kg -1·d -1, ganoderma triterpenoids: gavage 1 000 mg·kg -1·d -1). Morris water maze was used to test the spatial exploration and learning and memory ability of epileptic rats.Transmission electron microscopy was used to observe the ultrastructure of hippocampal neurons in epileptic rats.Immunofluorescence staining was used to observe expression levels of cofilin and SYN protein in hippocampus CA1 of rats. In addition, Western blot was used to detect the expression levels of cofilin, p-cofilin and synaptophysin(SYN) protein in hippocampus of rats. SPSS 17.0 software was used for statistical analysis. Repeated one-way ANOVA was used for comparing among groups, LSD test was used for pairwise comparisons. Results:Morris water maze results showed that there were statistically significant differences in escape latency, times of crossing the platform and time spent in the target quadrant among the groups( F=5.259, 8.240, 5.961, all P<0.05). Compared with the epilepsy model group, the escape latencies((20.31±7.39) s, (21.81±6.05) s, (17.66±4.76) s) of the ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group were shorter (all P<0.05), the numbers of crossing the platform ((4.63±1.41) times, (4.50±1.93) times, (5.50±1.77) times) were more (all P<0.05), the residence time in target quadrant ((31.91±5.00) s, (30.49±5.72) s, (35.70±5.34) s) were longer (all P<0.05). And the most obvious change was found in the GM1 combined with ganoderma triterpenoids group ( P<0.01). The results of transmission electron microscope showed that there were significant differences in the numbers of hippocampal neurons synapses, the synaptic gap, the density of postsynaptic membrane and length of active area of postsynaptic membrane among the groups( F=3.693, 7.201, 5.012, 4.033, all P<0.05). Compared with the epilepsy model group, the numbers of synapses ((8.00±1.79), (7.83±1.84), (8.50±1.87)) in the ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group were all more (all P<0.05), synaptic gap ((33.83±3.81)nm, (32.43±4.14)nm, (30.23±3.08)nm)were narrower, and the postsynaptic dense substances ((57.50±6.03)nm, (58.10±2.40)nm, (60.73±3.81)nm) were all thicker (all P<0.05). The length of active region of postsynaptic membrane ((271.66±11.80) nm, (279.06±13.58) nm) in ganoderma triterpenoid group and GM1 combined with ganoderma triterpenoids group were longer than that in epilepsy model group (both P<0.05). Immunofluorescence results showed that the average fluorescence intensity of cofilin in the epilepsy model group was higher than that in the blank control group, and the average fluorescence intensity of SYN was lower than that in the blank control group (both P<0.05). The average fluorescence intensity of cofilin in GM1 group and GM1 combined with ganoderma triterpenoids group were lower than that in epilepsy model group (both P<0.05), and the average fluorescence intensity of SYN in ganoderma lucidum triterpenoids combined with GM1 group was higher than that in epilepsy model group ( P<0.05). Western blot showed that the expression levels of cofilin protein in the epilepsy model group was higher than that in the blank control group ((1.454±0.080), (1.092±0.099), P<0.05), and the expression of p-cofilin and SYN were lower than those in the blank control group ((1.103±0.120) vs (1.420±0.934), (1.650±0.062) vs (1.958±0.062), both P<0.05). The expression of cofilin protein ((1.227±0.071), (1.262±0.078), (1.162±0.129), P<0.05) in ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group were lower than that in epilepsy model group, and the expression levels of p-cofilin(1.357±0.199) and SYN protein(1.873±0.010) in ganoderma triterpenoids combined with GM1 group were higher than that in epilepsy model group (both P<0.05). Compared with ganoderma lucidum triterpenoids group and GM1 group, there was no significant difference in each index of GM1 combined with ganoderma triterpenoids group (all P>0.05). Conclusion:GM1 combined with ganoderma triterpenoids may promote the synaptic plasticity of neurons, improve the learning and memory ability of epileptic rats.Combination medication is better than single medication in some observed indicators.

Objective:To explore the diagnostic accuracy of muscle ultrasound and plasma monocyte chemoattractant protein-1 (MCP-1) for ICU-acquired weakness (ICU-AW) in patients with sepsis.Methods:A prospective observational study was conducted. Patients with sepsis admitted to the intensive care unit (ICU) of Henan Provincial People's Hospital from April 2021 to October 2021 were enrolled. The demographic data were collected. The enrolled patients were evaluated with Medical Research Council (MRC) score every day until discharged from ICU. During this period, patients with total MRC score < 48 (for two consecutive times and a time interval of 24 hours) were divided into ICU-AW group, those with total MRC score ≥ 48 were served as non-ICU-AW group. On the 1st, 4th and 7th day following admission into ICU, ultrasound was used to measure the muscle linear thickness of the rectus femoris (RF-MLT), the cross sectional area of the rectus femoris (RF-CSA) and the muscle linear thickness of the vastus intermedius muscle (VI-MLT). And meanwhile, the plasmas samples of patients were collected to measure MCP-1 concentration by enzyme-linked immunosorbent assay (ELISA). The difference of each index was compared between the ICU-AW group and the non-ICU-AW group. The risk factors of ICU-AW in patients with sepsis were analyzed by binary Logistic regression. Besides, receiver operator characteristic curve (ROC curve) was plotted, the diagnostic value of ultrasound parameters and plasma MCP-1 level for ICU-AW in patients with sepsis was analyzed.Results:A total of 99 septic patients were enrolled, with 68 patients in the ICU-AW group and 31 patients in the non-ICU-AW group. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group tended to be older, and had higher sequential organ failure assessment (SOFA) score, higher acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, higher rates of septic shock, higher blood lactic acid and lower Glasgow coma score (GCS). Binary Logistic regression analysis showed that APACHEⅡ score and septic shock were the risk factors of ICU-AW for septic patients [odds ratio ( OR) and 95% confidence interval (95% CI) were 1.310 (1.138-1.509) and 0.232 (0.072-0.746), respectively, both P < 0.05]. The RF-MLT, RF-CSA and VI-MLT on the 1st, 4th and 7th ICU day was falling over time. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group had smaller RF-MLT on the 7th day [cm: 0.32 (0.22, 0.47) vs. 0.45 (0.34, 0.63), P < 0.05] and higher 7-day RF-CSA atrophy rate [25.85% (10.37%, 34.28%) vs. 11.65% (2.28%, 22.41%), P < 0.05]. According to ROC curve analysis, 7-day RF-MLT had diagnostic value for ICU-AW of septic patients. Area under ROC curve (AUC) was 0.688 (95% CI was 0.526-0.849); when the cut-off value was 0.41 cm, the sensitivity and the specificity were 66.7% and 68.4%. The levels of plasma MCP-1 in the ICU-AW group were significantly higher than those in the non-ICU-AW group on the 1st, 4th and 7th day. ROC curve analysis showed that the plasma MCP-1 levels on the 1st, 4th and 7th day played a significant role to diagnose ICU-AW for septic patients, the AUC and 95% CI were 0.732 (0.629-0.836), 0.865 (0.777-0.953), 0.891 (0.795-0.986), respectively. When the cut-off values were 206.3, 410.9, 239.5 ng/L, the sensitivity was 87.1%, 64.0%, 82.4%, and the specificity was 54.4%, 96.1%, 86.2%, respectively. Conclusion:The muscle mass parameters on the 7th day of bedside ultrasound and plasma MCP-1 levels had certain diagnostic values for ICU-AW in patients with sepsis.

Objective : To investigate the effect and mechanism of prenatal hypoxia on pulmonary artery vascular function in adult male offspring. Methods : Sprague⁃Dawley pregnant rats were randomly divided into hypoxia group and control group. Pregnant rats in the hypoxia group were housed in the hypoxia chamber ( a mixture of 89. 5% nitrogen gas and 10. 5% oxygen) from gestational day 10th to 20th. Pregnant rats in the control group were fed under normal oxygen. All animals were fed with standard rat food and tap water, and allowed to give birth naturally. After weaning , the male offspring were raised to 4 months old. Male offspring rats were anesthetized with chloral hydrate , and pulmonary artery was isolated for vascular function and molecular experiments. Results : Compared with the control group , phenylephrine ( PE) Ⅳ induced contraction response in prenatal hypoxic pulmonary artery was decreased (P < 0. 001) . There was no difference in acetyl choline (ACH) Ⅳand sodium nitrate (SNP) Ⅳinduced diastolic responses between the two groups. Compared with control group , Cav1 . 2 protein (P < 0. 01) and mRNA levels (P < 0. 001) in hypoxia group were reduced. Conclusion Prenatal hypoxia can lead to a decreased PE⁃induced vasoconstriction response in adult male offspring , which is related to the down⁃regulation of Cav1. 2 expression in pulmonary artery.