Objective To investigate alterations in serum NOV/CCN3 levels among women during mid-to-late pregnancy and elucidate its association with gestational diabetes mellitus(GDM)and pregnancy outcomes.Methods Based on the results of an oral glucose tolerance test(OGTT),we categorized 252 pregnant women into two groups:the GDM group and the control group.Within the GDM group,participants were further stratified based on pre-pregnancy body mass index levels and pregnancy outcomes.We collected clinical data for all study subjects and compared differences in general information,biochemical indicators,as well as NOV/CCN3 levels between these groups.Results The serum levels of NOV/CCN3 in the GDM group were significantly higher compared to those in the control group(P<0.001).Spearman correlation analysis revealed a positive association between serum NOV/CCN3 and pre-pregnancy body weight,pre-pregnancy body mass index,insulin resistance index,and total cholesterol;while a negative correlation was observed with insulin sensitivity index(P<0.05).Logistic regression analysis demonstrated that NOV/CCN3 is an independent risk factor for the development of GDM[OR=1.097,95%CI(1.020～1.179),P=0.013],as well as adverse pregnancy outcomes in GDM patients[OR=1.032,95%CI(1.020～1.045),P<0.001].ROC analysis indicated AUCs of 0.840 and 0.784 for these associations respectively(P<0.05).Conclusions Serum levels of NOV/CCN3 in pregnant women at mid-to late-stage are associated with obesity,insulin resistance,and glucose-lipid metabolism,suggesting a potential role of NOV/CCN3 in glycolipid metabolism during gestational diabetes mellitus(GDM).These findings provide novel insights for assessing the occurrence of GDM and predicting pregnancy outcomes in mid-to late-stage pregnancies.

Objective By using ultrasonography to calculate the ratio of optic nerve sheath diameter(ONSD)at 3 mm behind eyeball to the eyeball transverse diameter(ETD),based on which to evaluate the effect of dexmedetomidine on intracranial pressure(ICP)in patients with intracranial aneurysm after receiving interventional embolization under general anesthesia.Methods A total of 40 patients with intracranial aneurysm,who were scheduled to receive interventional embolization under general anesthesia at the Affiliated Lihuili Hospital of Ningbo University of China from May 2023 to November 2023,were selected for this study.By using random number table method,the patients were divided into control group(group C)and dexmedetomidine group(group D)with 20 patients in each group.Standardized anesthesia strategy was adopted in both groups.For patients of group D,a loading dose of dexmedetomidine was pumped at a velocity of 1 μg/(kg·h)for 10 min before the surgery,the pumping was continued at 0.5 μg/(kg·h)velocity during the operation,and the pumping stopped half an hour before the end of the operation.For patients of group C,the same anesthesia strategy was used,while no any special treatment was given.At the different time points,including before awakening(T0),immediately after extubation(T1),and 5 min(T2),10 min(T3),15 min(T4)after extubation,ONSD at 3 mm behind eyeball and ETD were measured by transorbital ultrasonography,and ONSD/ETD ratio was calculated to evaluate ICP.The mean arterial pressure(MAP),heart rate(HR),blood oxygen saturation(SPO2),severity of cough,and extubation time were recorded at the time to remove the catheter.Results Compared with the data obtained at T0,the ONSD/ETD ratios obtained at T1 and T2 were increased in both groups(P＜0.05),while the ONSD/ETD ratios obtained at other time points were not significantly different from the ONSD/ETD ratio obtained at T0(P＞0.05).Compared with Group C,in Group D the ONSD/ETD ratios obtained at T1 and T2 were smaller,the differences were statistically significant(P＜0.05).The incidence of moderate to severe cough in Group D was lower than that in Group C(P＜0.05).Compared with Group C,in Group D the HR and MAP determined at the time of removing catheter were lower(P＜0.05).The extubation time in Group D was longer than that in group C,the difference was statistically significant(P＜0.05).Conclusion ONSD/ETD ratio calculated by ultrasono-graphy can objectively reflect the changes of ICP during the extubation period.Dexmedetomidine can reduce the elevation degree of ICP through effectively inhibiting cough reflex and circulatory fluctuation during tracheal extubation.However,dexmedetomidine may increase the incidence of adverse events such as bradycardia,delayed extubation,etc.

Objective To investigate alterations in serum NOV/CCN3 levels among women during mid-to-late pregnancy and elucidate its association with gestational diabetes mellitus(GDM)and pregnancy outcomes.Methods Based on the results of an oral glucose tolerance test(OGTT),we categorized 252 pregnant women into two groups:the GDM group and the control group.Within the GDM group,participants were further stratified based on pre-pregnancy body mass index levels and pregnancy outcomes.We collected clinical data for all study subjects and compared differences in general information,biochemical indicators,as well as NOV/CCN3 levels between these groups.Results The serum levels of NOV/CCN3 in the GDM group were significantly higher compared to those in the control group(P<0.001).Spearman correlation analysis revealed a positive association between serum NOV/CCN3 and pre-pregnancy body weight,pre-pregnancy body mass index,insulin resistance index,and total cholesterol;while a negative correlation was observed with insulin sensitivity index(P<0.05).Logistic regression analysis demonstrated that NOV/CCN3 is an independent risk factor for the development of GDM[OR=1.097,95%CI(1.020～1.179),P=0.013],as well as adverse pregnancy outcomes in GDM patients[OR=1.032,95%CI(1.020～1.045),P<0.001].ROC analysis indicated AUCs of 0.840 and 0.784 for these associations respectively(P<0.05).Conclusions Serum levels of NOV/CCN3 in pregnant women at mid-to late-stage are associated with obesity,insulin resistance,and glucose-lipid metabolism,suggesting a potential role of NOV/CCN3 in glycolipid metabolism during gestational diabetes mellitus(GDM).These findings provide novel insights for assessing the occurrence of GDM and predicting pregnancy outcomes in mid-to late-stage pregnancies.

Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

Objective To discuss the application of the"rotating guidewire and correcting the filter recovery hook direction technique"("rotation-correction loop technique"for short),a technique invented by the authors in clinical practice,in the retrieval of complex inferior vena cava filter(IVCF),and to discuss its technical skills and advantages.Methods The clinical data of 417 patients carrying an IVCF,who were admitted to the Department of Vascular Surgery of Second Hospital of Shanxi Medical University of China to retrieve IVCF between January 2022 and December 2022,were retrospectively analyzed.Taking the time spent on the retrieval of IVCF and the intraoperative radiation dose as the evaluation indicators,the advantages and disadvantages of the standard filter retrieval technique,the"rotation-correction loop technique"and the other loop-assisted techniques were compared.Results Both the intraoperative radiation dose and the time spent on the retrieval of IVCF using"rotation-correction loop technique"were remarkably lower than those of other loop-assisted techniques(P＜0.000 1).Conclusion For the retrieval of complex IVCF,especially for the IVCF which is heavily tilted and/or its recovered hook is attached to the vascular wall,the use of"rotation-correction loop technique"can shorten the time spent on the the retrieval of IVCF and reduce the intraoperative radiation dose.This technique carries high safety and practicability,the device is simple and it can be manipulated by single physician,which is conducive to clinical application and promotion.(J Intervent Radiol,2024,33:289-294)

[This corrects the article DOI: 10.1016/j.apsb.2024.04.021.].

Objective To clarify the effect and mechanism of tumor antigen-loaded dendritic cells (Ag-DCs) combined with cytokine-induced killers (CIKs) on the killing of esophageal cancer tumor cells. Methods Peripheral blood DCs and CIKs were induced and cultured, and the DCs were loaded with tumor antigen to obtain Ag-DCs, and Ag-DCs were co-cultured with CIKs. The experiment was divided into CIK group, DC combined with CIK group, Ag-DC combined with CIK group. Flow cytometry was used to detect the phenotype of cells. MTT assay was employed to determine the killing activity against EC9706 cells. Annexin V-FITC/PI double staining was used to detect the apoptosis rate of cells, immunofluorescence staining to detect the expression of phosphorylated apoptotic signal-regulated kinase 1 (p-ASK1) and Western blot analysis to detect the expression of ASK1 pathway related proteins. A nude mouse model of esophageal cancer transplantation tumor was constructed and divided into control group, DC combined with CIK group and Ag-DC combined with CIK group. The corresponding immune cells were injected into the tail vein for treatment and the tumor volume was measured every 2 days. After 21 days, all nude mice were sacrificed with the tumors taken out. HE staining was used to observe the tumor pathological changes and immunohistochemical staining was performed to detect the expression of ki67 and ASK1 in the tumor tissue. Results Comparedwith the CIK group alone and the DC combined with CIK group, the ratio of CD3⁺ CD8⁺ and CD3⁺ CD56⁺ in the cells significantly increased after Ag-DCs and CIKs co-culture, along with the increased killing rate of EC9706 cells, increased apoptosis rate of EC9706 cells, and the improved activation level of ASK1. Compared with the CIK group and the DC combined with CIK group, the growth of the transplanted tumor in nude mice treated with Ag-DCs combined with CIKs was significantly inhibited, and after 21 days, it was observed that the tumor tissue mass in this group was relatively smaller, with sparsely arranged cells in the tumor tissue and a decline in the positive rate of ki67 in tumor tissue, while the positive rate of ASK1 was significantly increased. Conclusion Co-cultivation of tumor antigen-loaded DCs with CIKs can significantly increase the killing activity of esophageal cancer tumor cells. The mechanism of action may be related to the activation of the ASK1 pathway.
Animals ; Humans ; Mice ; Antigens, Neoplasm ; Cytokine-Induced Killer Cells ; Cytokines/metabolism* ; Cytotoxicity, Immunologic ; Dendritic Cells ; Esophageal Neoplasms/therapy* ; Ki-67 Antigen ; Mice, Nude

Osteoporosis is a common extrahepatic complication of liver cirrhosis, and it not only increases the economic burden of patients, but also brings adverse effects on their quality of life and prognosis. Recent studies have shown that sarcopenia, adiponectin, leptin, irisin, and inflammatory factors are involved in the development of osteoporosis in patients with liver cirrhosis, and commonly used anti-osteoporosis drugs include calcium supplement, vitamin D, and bisphosphonates. This article reviews the advances in the risk factors, pathogenesis, and treatment of liver cirrhosis with osteoporosis and points out that there are still controversies over the influence of some factors on osteoporosis, and further studies are needed to explore related pathogeneses and safe and effective treatment regimens.

As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.
Humans ; Lung Neoplasms/therapy* ; Tumor Microenvironment ; Neoplasms/drug therapy* ; Immunotherapy/methods*

Objective:To compare the clinical efficacy of unilateral biportal endoscopy (UBE) and uniportal endoscopy (UE) for unilateral laminotomy for bilateral decompression (ULBD) in the treatment of lumbar spinal stenosis.Methods:Data of 82 patients with lumbar spinal stenosis treated by ULBD under UBE or UE from January 2020 to June 2021 in Dalian Central Hospital affiliated to Dalian Medical University and the First Hospital affiliated to Wenzhou Medical University were retrospectively analyzed, including 36 males and 46 females, aged 63.3±7.5 years (range, 47-81 years). According to the surgical procedure, they were divided into UBE group (42 cases), including 20 males and 22 females; aged 63.2±7.6 years (range, 47-81 years) and UE group (40 cases), including 16 males and 24 females; aged 63.5±7.5 years (range, 48-80 years). Operation time, hospital stay and surgical complications were compared between the two groups. Visual analogue scale (VAS) of low back and leg pain before surgery, 1 day, 7 d, 1 month and 6 months after surgery, and Oswestry disability index (ODI) before surgery, 1 month and 6 months after surgery were compared. Dural sac area before and after surgery, resection angle of ipsilateral facet joint, decompression rate of disc space and bone lateral recess were calculated.Results:All patients were operated successfully. In the UBE group, the operation time was 63.1±7.0 min, and the hospital stay was 3.9±0.9 d. The UE group was 61.2±6.2 min and 3.7±0.9 d, respectively ( t=1.31, P=0.195; t=1.24, P=0.217). The VAS of back and legs pain in UBE group decreased from 7.19±0.97 before operation to 3.43±0.63 points at postoperative 1 day, 1.71±0.60 at postoperative 7 d, 1.33±0.48 at postoperative 1 month and 1.36±0.48 points at postoperative 6 months ( F=352.29, P<0.001). The VAS score of the UE group decreased from 6.85±0.89 points before operation to 2.45±0.75 points at postoperative 1 day, 1.75±0.59 points at postoperative 7 d, 1.33±0.47 points at postoperative 1 month and 1.28±0.45 points at postoperative 6 months ( F=291.44, P<0.001). The VAS of low back and leg pain was higher in the UBE group than in the UE group at 1 day postoperatively ( t=6.41, P<0.001), and the difference was not statistically significant at 7 d postoperatively ( t=-0.27, P=0.786). The ODI of UBE group decreased from 66.62%±4.98% before operation to 21.81%±2.61% at postoperative 1 month and 11.62%±2.31% at postoperative 6 months ( F=1991.35, P<0.001). The ODI score of UE group decreased from 64.35%±5.16% before operation to 22.85%±3.26% at postoperative 1 month and 11.15%±2.86% at postoperative 6 months ( F=1931.18, P<0.001). The postoperative dural sac area of the UBE and UE groups was 135.1±10.0 mm 2 and 120.9±10.4 mm 2 ( t=6.30, P<0.001). The resection angle of ipsilateral facet joint was 69.3°±4.9° and 94.3°±4.1° in the two groups, respectively, with a statistically significant difference ( t=-25.00, P<0.001). The decompression rate of ipsilateral disk-flavum space was 39.0%±3.0% and 38.7%±3.3% in the two groups ( t=1.52, P=0.314). On the contralateral side was 41.6%±3.3% and 22.8%±3.2% ( t=26.32, P<0.001), respectively. The ipsilateral osseous side fossa decompression rate in the two groups were 70.0%±4.8% and 59.3%±3.9% ( t=15.64, P<0.001), the contralateral were 73.0%±3.4% and 48.4%±4.3% ( t=28.86, P<0.001). There was no significant difference in the decompression rate of ipsilateral disco-flavum space or bony lateral recess between the UBE group and the contralateral group ( t=-1.40, P=0.174; t=-1.72, P=0.096), while the decompression rate of discoflavum space and bony side recess on the ipsilateral side of UE group were higher than those on the contralateral side ( t=28.51, P<0.001; t=13.95, P<0.001). Conclusion:Both UE-ULBD and UBE-ULBD have good short-term clinical efficacy in patients with lumbar spinal stenosis. UB is better than UBE in early postoperative pain relief. However, UBE shows better imaging performance in decompression effect and better retention of facet joints.