Objective The risk evaluation indicators for the occurrence of diaphragm dysfunction in ICU patients was constructed to provide a reference for the establishment of the disease risk evaluation tools for diaphragm dysfunction.Methods The literature related to diaphragm dysfunction from CNKI,Wanfang Data,PubMed,Embase and Web of Science from the establishment of databases to November 11 th,2022 was systematically searched.After the first draft was determined through the literature review method,the first draft of the indicators was revised by brainstorming,with the opinions of 10 medical and nursing experts from May to June 2023.From June to July 2023,the content and weight of risk evaluation indicators of diaphragmatic dysfunction in ICU patients were determined through expert letter inquiry and hierarchical analysis.Results 35 experts completed the first round of letter inquiry,and 34 experts completed the second round of letter inquiry.The recovery rates of the valid questionnaires in the 2 rounds of expert correspondence were 92.1％and 97.1％,respectively,and the expert authority coefficients were 0.884 and 0.904,respectively,and the Kendall harmony coefficients of all indicators were 0.356～0.570 and 0.369～0.604,respectively(all P＜0.001).The final constructed risk evaluation indicators of diaphragm dysfunction in ICU patients includes 7 first-level indicators,34 secondary indicators and 34 tertiary indicators.Conclusion The risk evaluation index of diaphragm dysfunction in ICU patients constructed in this study is comprehensive,specific,scientific and applicable,which can guide medical staff to conduct early risk evaluation of diaphragm function in ICU patients,and provide references for the establishment of disease risk assessment tools for diaphragm function.

Objective To assess the correlation between wall shear stress(WSS)in the internal carotid artery and neovascularization of carotid plaque using color ultrasound imaging.Methods A total of 99 patients diag-nosed with carotid atherosclerotic plaque(CAP)were prospectively selected between July 2021 and September 2023.All patients underwent comprehensive carotid imaging including color ultrasound,conventional ultrasound,and carotid contrast-enhanced ultrasound(CEUS).Based on the presence or absence of intraplaque neovasculariza-tion(IPN)in patients with ischemic cerebrovascular disease,they were categorized into the forming group and non-forming group.Comparative analysis was performed on wall shear stress(WSS)values and clinical data between these two groups to identify factors influencing IPN formation in the carotid artery among patients with ischemic cere-brovascular disease,while also assessing the predictive value of average WSS for IPN formation.Results Among 99 patients with ischemic cerebrovascular disease,carotid artery IPN was observed in 23 cases,while the remaining 76 cases did not exhibit carotid artery IPN.The formation group demonstrated significantly higher levels of white blood cell count,plaque thickness,plaque length,stenosis≥70%ratio,C-reactive protein,and matrix metallopro-teinase-9 to tissue inhibitor of matrix metalloproteinase-1(MMP-9/TIMP-1)ratio compared to the non-formation group(P<0.05).Logistic regression analysis revealed that mean wall shear stress(OR=4.545;95%CI:1.998～10.339),stenosis severity(OR=2.765;95%CI:1.215～6.290),C-reactive protein levels(OR=3.047;95%CI:1.339～6.930),and MMP-9/TIMP-1 ratio(OR=3.543;95%CI:1.558～8.060)were significant influencing factors for carotid artery IPN formation in patients with ischemic cerebrovascular disease(P<0.05).The receiver operating characteristic curve(ROC)analysis revealed that the area under the curve(AUC)for average WSS in predicting carotid artery intraplaque neovascularization formation in patients with ischemic cerebrovascular disease was 0.797(P<0.05).At an average WSS of 10.23 dyne/cm2,the maximum specificity and sensitivity were deter-mined to be 85.53%and 78.26%,respectively.Conclusion The mean WSS of internal carotid artery has a good value in predicting the formation of carotid IPN in patients with ischemic cerebrovascular disease.

Evoked Potentials ; Social Isolation ; Attention ; Humans

Objective:To explore the genetic basis for a fetus with Cardiac valvular dysplasia type 1 (CVDP1).Methods:A CVDP1 fetus identified at the Ningbo Women and Children′s Hospital on July 7, 2022 was selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were subjected to trio-whole exome sequencing (trio-WES), and candidate variants were verified by Sanger sequencing.Results:The fetus had exhibited generalized edema, complex cardiac malformation, abdominal effusion, and enhanced intestinal and renal parenchymal echoes. Trio-WES revealed that it has harbored compound heterozygous variants of the PLD1 gene, namely c. 2977C>T (p.R993*) and c. 1460G>A (p.W487*), which were respectively inherited from its father and mother. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 2977C>T (p.R993*) variant was evaluated to be likely pathogenic (PVS1_Moderate+ PM2_Supporting+ PM3+ PP4), whilst the c. 1460G>A (p.W487*) variant was evaluated to be pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The c. 2977C>T (p.R993*) and c. 1460G>A (p.W487*) compound heterozygous variants of the PLD1 gene probably underlay the CVDP1 in the fetus. Above discovery has enriched the mutational spectrum of the PLD1 gene and provided a guidance for genetic counseling and prenatal diagnosis in this family.

OBJECTIVE To explore the mechanism by which casticin （CAS） promotes wound healing in superficial second- degree burned rats through phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT）/mammalian target of rapamycin （mTOR） signaling pathway. METHODS Rats were randomly assigned to a control group （physiological saline）， a model group （5% sodium carboxymethyl cellulose blank matrix）， low- and high-dose CAS groups （15 mL of CAS solution at concentrations of 30 and 60 mmol/L， respectively）， a high dose CAS plus LY294002 group [a mixture of 15 mL CAS solution （60 mmol/L） and PI3K inhibitor LY294002 solution （20 μmmol/L）]， and a positive control group （thick application of Jingwanhong ointment 0.5-1.0 cm）， with 15 rats in each group. Except for the control group， the other groups were subjected to a superficial second-degree burn rat model by igniting a mixture of burn fuel on the skin surface， and the administration was applied topically within two hours after the burn. After 28 days of administration， the wound healing rate of the burned rats was calculated， the histopathological changes in the central tissue of the rat’s burned wound were observed， and the levels of tumor necrosis factor α （TNF-α）， interleukin-1β （IL- 1β）， IL-6， matrix metalloproteinase-2 （MMP-2）， MMP-9 and vascular endothelial growth factor （VEGF） in the serum of rat were detected. The phosphorylation levels of related proteins in the PI3K/AKT/mTOR signaling pathway in the burned tissue of the rats were also detected. RESULTS Compared with the control group， the rats in the model group showed epidermal and superficial dermal damage in skin tissue， poor healing status， inflammatory cell infiltration， and incomplete tissue structure. The levels of IL-6， IL-1β， TNF-α， MMP-2 and MMP-9 in the serum were significantly increased （P＜0.05）， and the levels of VEGF in the serum and the phosphorylation levels of E-mail：caodongsheng@ahmu.edu.cn PI3K， AKT， mTOR proteins in the central tissue of the burned wound were significantly decreased （P＜0.05）. Compared with the model group， the pathological changes and the levels of the above indicators in the serum and central tissue of the burned wound in the CAS low- and high-dose groups were significantly reversed （P＜0.05）， and the changes in the CAS high-dose group were significantly more pronounced than those in the CAS low- dose group （P＜0.05）. The addition of the PI3K inhibitor LY294002 could reverse the promoting effect of CAS on the wound healing of superficial second-degree burned rats （P＜0.05）. CONCLUSIONS CAS can promote the healing of superficial second- degree burned wounds in rats， and its mechanism of action may be related to the activation of the PI3K/AKT/mTOR signaling pathway.

Objective To discuss the clinical application of intravoxel incoherent motion-diffusion weighted imaging(IVIM-DWI)in evaluating the efficacy and prognosis of transcatheter arterial chemoembolization(TACE)using different embolization materials for the treatment of hepatocellular carcinoma(HCC).Methods The clinical data of a total of 84 patients with inoperable HCC,who received TACE treatment at the Second Affiliated Hospital of Shandong First Medical University of China and the First Affiliated Hospital of Xinjiang Medical University of China between June 30,2019 and December 30,2022,were collected.According to the patient's condition,different embolization materials were used during TACE.IVIM-DWI check-up was performed before treatment as well as at one,6,12 months after treatment.Based on the fixed b-value set by IVIM-DWI sequence,the ADC value of the order index model for different embolization materials and the pure diffusion coefficient of double exponential model(D value),the pseudo-diffusion coefficient(D*value)and perfusion fraction(f value)were analyzed.According to modified Response Evaluation Criteria in Solid Tumors(mRECIST)and the embolization material used,the patients were divided into the stable group and progression group,and the changes in the ADC value,D value,D*value and f value were compared between the two groups.Multivariate Cox regression analysis was used to analyze the four clinical parameters(including age,Child-Pugh grade,AFP level and tumor size)and the eight functional quantitative indexes(including preoperative and postoperative ADC value,D value,D* value and f value)so as to determine the IVIM parameters with prognostic predictive value.Receiver operating characteristic(ROC)was adopted to analyze the diagnostic value and cut-off value of IVIM parameters with predictive value.Results After treatment,the ADC value of drug-loaded microspheres group(n=36)was significantly higher than that of iodized oil group(n=27),the D*value of drug-loaded microspheres group and iodized oil group was remarkably lower than that of PVA particle group(n=21),and the f value of drug-loaded microspheres group was strikingly lower than that of iodized oil group,the differences were statistically significant(all P＜0.01).In the stable group,the efficacy of drug loaded microspheres group was obviously better than that of the iodized oil group and the PVA particle group.In the progression group,the iodized oil group was more likely to develop disease progression than the drug-loaded microspheres group and the PVA particle group.The preoperative f value in the stable group was prominently higher than that in the progression group(P=0.005),and the postoperative ADC value in the stable group was obviously higher than that in the progression group(P=0.029).ROC analysis showed that the median follow-up time in the drug-loaded microspheres group,iodized oil group,and PVA particle group was 30,19,and 26 months respectively,the overall average survival time was 25 months,and the difference was statistically significant(P＜0.01).Multivariate Cox regression analysis showed that the preoperative D value(AUC=0.878),D*value(AUC=0.554)and postoperative D value(AUC=0.791),D*value(AUC=0.552),f value(AUC=0.467)were the independent factors affecting the short-term efficacy of TACE(all P＜0.05).The preoperative and postoperative D value had higher diagnostic efficacy,while a preoperative D value of＜0.505×10-3 mm2/s and a postoperative D value of＜0.785×10-3 mm2/s predicted a poor prognosis.Conclusion The preoperative and postoperative D value is the optimal parameter for predicting the curative efficacy of TACE using different embolization materials for the treatment of HCC.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

As a commonly used traditional Chinese medicine,Alpinia oxyphylla is widely used as both medicine and edible resources.A.oxyphylla has the effects of warming the kidney,consolidating essence,contracting urine,warming the spleen,stopping diarrhea and absorbing saliva,which mainly treated diseases caused by kidney deficiency and spleen cold.A.oxyphylla is rich in chemical components,mainly including 194 volatile oil,121 terpenoids(including 111 sesquiterpenoids),19 diphenylheptanes,ten flavonoids,ten bases and nucleosides,four steroids,eight glycosides and 13 organic acids.It has a wide range of pharmacological effects such as anti-AD/PD,anti-tumor,anti-inflammatory,antioxidant,etc.This article reviews the chemical components and pharmacological effects of A.oxyphylla,in order to provide reference for its further development and rational application.

Objective To investigate the protective effect of Toll-like receptor (TLR)2/TLR9 agonists,Pam2 CSK4(Pam)and CpG ODN (CpG)on mice infected with Acinetobacter baumannii (Ab)in the lungs.Methods Female C57 mice (6～8 weeks old)were randomly divided into PBS,Pam,CpG and Pam+CpG groups.In 24 h after intranasal immunization with different doses of the corresponding agonists,the mice were given a lethal dose of Ab infection in the lungs,and the survival rates of the mice were observed.A sublethal dose lung infection model of Ab was then established,and the bacterial colonization in the blood,lungs,liver,kidneys and spleen was measured respectively in the mice after infection.HE staining was used to observe the pathological damages in the lungs and kidneys.The protective effect of the agonists in the immunized mice against Ab was examined at 1,3 and 7 d after immunization to explore the protective time window.Pam+CpG was used to stimulate A549 cells and RAW264.7 cells to investigate the killing or phagocytic effects on Ab.Results Compared to PBS,Pam+CpG treatment significantly improved the survival rate of the mice after a lethal dose of Ab lung infection (P<0.05,P<0.01 ),reduced bacterial colonization in the blood (P<0.01 ),lungs (P<0.01 ),liver (P<0.01 ),kidneys (P<0.01 )and spleen (P<0.01 )in the mice after sublethal challenge,and alleviated pathological damage caused by infection. Immunization at 1 or 3 d before infection significantly improved the survival rate (P<0.05 ),and the protective effect was the best in 3 d after immunization.Furthermore,compared to single PBS,Pam and CpG immunization,Pam+CpG significantly promoted the killing and phagocytic effects of A549 epithelial cells and RAW264.7 cells,respectively,against Ab (P<0.01 ).Conclusion Combined application of TLR2/TLR9 agonists exerts a significant protective effect on both lethal and sublethal infections of Ab,which might be by its promoting the killing or phagocytic effect of lung epithelial cells and macrophages against Ab.

Objective To construct lipid nanoparticles(lipopeptide-lipid nanoparticle,LP-LNP)with novel lipopeptides as adjuvants,and initially explore their synergistic effect on mRNA vaccines.Methods Two novel lipopeptides,SS-10 and SQ18,were designed and synthesized.Microfluidic technology was used to encapsulate lipopeptides in different proportions,as well as mRNAs encoding enhanced green fluorescent protein(eGFP),firefly luciferase(F-luc),and ovalbumin(OVA)into lipid nanoparticles to construct an mRNA delivery system with novel lipopeptides as adjuvants(LP-LNP).The particle size and polydispersity coefficient of LP-LNP were measured using dynamic light scattering.The activation effect on Toll-like receptors 2(TLR2)was detected using HEK-BlueTM mTLR2 reporter cells to screen the optimal lipopeptide ratio.The preferred LP-LNP-eGFP-mRNA was transfected into HEK293T cells,and the expression of eGFP was observed under a fluorescence microscope.In vivo imaging was used to investigate the expression level of LP-LNP-F-luc-mRNA in mice.Flow cytometry was used to evaluate the ability of LP-LNP-OVA-mRNA to induce the maturation of dendritic cells(DCs)in draining lymph nodes and cross-presentation of antigens after immunization.Results Lipopeptides SQ18 and SS-10 were incorporated into LNP at 0.50％and 0.75％molar ratios,respectively,to obtain LP-LNP with uniform particle size,high encapsulation efficiency,and good in vitro safety.The ability of this formulation to activate TLR2 was significantly stronger than the positive control Pam2CSK4(P＜0.01).The preferred LP-LNP obtained effective in vitro transfection,and LP-LNP prepared with SQ18 at 0.50％molar ratio had significantly better in vivo transfection efficiency than traditional LNP(P＜0.01),and significantly promoted the maturation of DCs in draining lymph nodes and cross-presentation of antigens(P＜0.05).Conclusion LP-LNP with novel lipopeptides as adjuvants can enhance the delivery capacity of mRNA and further improve the immune effect of mRNA vaccines.