Air embolism after CT-guided localization of pulmonary ground-glass nodules.

OBJECTIVE: To investigate the incidence of air embolism (AE) related to CT-guided localization of pulmonary ground-glass nodules (GGNs) prior to video-assisted thoracoscopic surgery (VATS). METHODS: The data of all patients who received CT-guided localization of GGNs before VATS from May 2020 to October 2021 were retrospectively analyzed. RESULTS: A total of 1395 consecutive patients with 1553 GGNs were enrolled. AEs occurred in seven patients (0.5%). In four of the seven patients with AE, the embolism was detected before the patients left the CT table and emergency treatments were carried out. Among them, one patient had chest tightness and unilateral limb dyskinesia, one patient had convulsions and transient loss of consciousness, and two patients had no definite clinical symptoms. After a short-term high-flow oxygen inhalation, the clinical symptoms of two patients with symptomatic AE disappeared and two patients with asymptomatic AE did not show any symptoms. In the remaining three patients with AE, the embolism were detected retrospectively when evaluating the images in the PACS for this study. Fortunately, these three patients never developed clinical symptoms related to AE. All seven patients with AE underwent VATS on the day of localization and all GGNs were successfully removed under the guidance of markers. CONCLUSION: The incidence of AE related to CT-guided localization of GGNs was 0.5%, which was significantly higher than expected. Post-localization whole thoracic CT should be performed and observed carefully so as to avoid missed AE and delayed treatment. ADVANCES IN KNOWLEDGE: The incidence of AE related to CT-guided localization of GGNs was 0.5%. In order to timely detect AE, whole thoracic CT scan rather than local CT in the lesion area should be performed after localization. A small amount of AE may be missed if the post- localization CT images are not carefully observed.

Dysregulation of EZH2/miR-138-5p Axis Contributes to Radiosensitivity in Hepatocellular Carcinoma Cell by Downregulating Hypoxia-Inducible Factor 1 Alpha (HIF-1α).

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase involved in cell proliferation, invasion, angiogenesis, and metastasis in various cancers, including hepatocellular carcinoma (HCC). However, the role and molecular mechanisms of EZH2 in HCC radiosensitivity remain unclear. Here, we show that EZH2 is upregulated in HCC cells and the aberrantly overexpressed EZH2 is associated with the poor prognosis of HCC patients. Using miRNA databases, we identified miR-138-5p as a regulator of EZH2. We also found that miR-138-5p was suppressed by EZH2-induced H3K27me3 in HCC cell lines. MiR-138-5p overexpression and EZH2 knockdown enhanced cellular radiosensitivity while inhibiting cell migration, invasion, and epithelial-mesenchymal transition (EMT). Analysis of RNA-seq datasets revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was the main enrichment pathway for differential genes after miR-138-5p overexpression or EZH2 knockdown. Expression level of HIF-1α was significantly suppressed after miR-138-5p overexpression or silencing of EZH2. HIF-1α silencing mitigated resistance of HCC cells and inhibited EMT. This study establishes the EZH2/miR-138-5p/HIF-1α as a potential therapeutic target for sensitizing HCC to radiotherapy.

Bioelectrical impedance analysis-guided fluid management promotes primary fascial closure after open abdomen: a randomized controlled trial.

BACKGROUND: Fluid overload (FO) after resuscitation is frequent and contributes to adverse outcomes among postinjury open abdomen (OA) patients. Bioelectrical impedance analysis (BIA) is a promising tool for monitoring fluid status and FO. Therefore, we sought to investigate the efficacy of BIA-directed fluid resuscitation among OA patients. METHODS: A pragmatic, prospective, randomized, observer-blind, single-center trial was performed for all trauma patients requiring OA between January 2013 and December 2017 to a national referral center. A total of 140 postinjury OA patients were randomly assigned in a 1:1 ratio to receive either a BIA-directed fluid resuscitation (BIA) protocol that included fluid administration with monitoring of hemodynamic parameters and different degrees of interventions to achieve a negative fluid balance targeting the hydration level (HL) measured by BIA or a traditional fluid resuscitation (TRD) in which clinicians determined the fluid resuscitation regimen according to traditional parameters during 30 days of ICU management. The primary outcome was the 30-day primary fascial closure (PFC) rate. The secondary outcomes included the time to PFC, postoperative 7-day cumulative fluid balance (CFB) and adverse events within 30 days after OA. The Kaplan-Meier method and the log-rank test were utilized for PFC after OA. A generalized linear regression model for the time to PFC and CFB was built. RESULTS: A total of 134 patients completed the trial (BIA, n = 66; TRD, n = 68). The BIA patients were significantly more likely to achieve PFC than the TRD patients (83.33% vs. 55.88%, P < 0.001). In the BIA group, the time to PFC occurred earlier than that of the TRD group by an average of 3.66 days (P < 0.001). Additionally, the BIA group showed a lower postoperative 7-day CFB by an average of 6632.80 ml (P < 0.001) and fewer complications. CONCLUSION: Among postinjury OA patients in the ICU, the use of BIA-guided fluid resuscitation resulted in a higher PFC rate and fewer severe complications than the traditional fluid resuscitation strategy.

Predictors of irreversible intestinal resection in patients with acute mesenteric venous thrombosis.

BACKGROUND: Acute mesenteric venous thrombosis (AMVT) can cause a poor prognosis. Prompt transcatheter thrombolysis (TT) can achieve early mesenteric revascularization. However, irreversible intestinal ischemia still occurs and the mechanism is still unclear. AIM: To evaluate the clinical outcomes of and to identify predictive factors for irreversible intestinal ischemia requiring surgical resection in AMVT patients treated by TT. METHODS: The records of consecutive patients with AMVT treated by TT from January 2010 to October 2017 were retrospectively analyzed. We compared patients who required resection of irreversible intestinal ischemia to patients who did not require. RESULTS: Among 58 patients, prompt TT was carried out 28.5 h after admission. A total of 42 (72.4%) patients underwent arteriovenous combined thrombolysis, and 16 (27.6%) underwent arterial thrombolysis alone. The overall 30-d mortality rate was 8.6%. Irreversible intestinal ischemia was indicated in 32 (55.2%) patients, who had a higher 30-d mortality and a longer in-hospital stay than patients without resection. The significant independent predictors of irreversible intestinal ischemia were Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio = 2.368, 95% confidence interval: 1.047-5.357, P = 0.038) and leukocytosis (odds ratio = 2.058, 95% confidence interval: 1.085-3.903, P = 0.027). Using the receiver operating characteristic curve, the cutoff values of the APACHE II score and leukocytosis for predicting the onset of irreversible intestinal ischemia were calculated to be 8.5 and 12 × 109/L, respectively. CONCLUSION: Prompt TT could achieve a favorable outcome in AMVT patients. High APACHE II score and leukocytosis can significantly predict the occurrence of irreversible intestinal ischemia. Therefore, close monitoring of these factors may help with the early identification of patients with irreversible intestinal ischemia, in whom ultimately surgical resection is required, before the initiation of TT.

Downregulation of GEP100 Improved the Growth Inhibition Effect of Erlotinib Through Modulating Mesenchymal Epithelial Transition Process in Pancreatic Cancer.

OBJECTIVE: The epidermal growth factor receptor is overexpressed in the majority of pancreatic cancer. Epidermal growth factor receptor tyrosine kinase inhibitor erlotinib was approved to treat patients combining with gemcitabine. However, the sensitivity is low. Here, we try to reveal the regulatory role of guanine nucleotide exchange protein 100 (GEP100) in erlotinib sensitivity. METHODS: We investigated the correlation between GEP100 expression and sensitivity to erlotinib in different pancreatic cancer cell lines, followed by examination of the effect of GEP100 on erlotinib sensitivity by establishing the stable knocked-down cell line. The expression level of epithelial mesenchymal transition-related protein was examined by Western blot, and the regulatory mechanism was investigated by short hairpin RNA. Xenograft experiment was also performed in nude mice. RESULTS: We identified a significant correlation between sensitivity to erlotinib and expression of GEP100. GEP100 downregulation increased its sensitivity to erlotinib. E-cadherin short hairpin RNA treatment inhibited this sensitivity. Immunohistochemical staining showed a mutual exclusive expression pattern of GEP100 and E-cadherin in human pancreatic cancer tissues. Xenograft showed that downregulation of GEP100 enhanced the growth inhibition of erlotinib in nude mice. CONCLUSIONS: Our results suggested that GEP100 and E-cadherin have the predictive value for responsiveness to erlotinib in pancreatic cancer.

Minimally Invasive Cochlear Implantation Assisted by Bi-planar Device: An Exploratory Feasibility Study in vitro.

BACKGROUND: A single drilled tunnel from the lateral mastoid cortex to the cochlea via the facial recess is essential for minimally invasive cochlear implant surgery. This study aimed to explore the safety profile of this kind of new image-guided and bi-planar device-assisted surgery procedure in vitro. METHODS: Image-guided minimally invasive cochlear implantations were performed on eight cadaveric temporal bone specimens. The main procedures were: (1) temporal bone specimens were prepared for surgery and fiducial markers were registered. (2) computed tomography (CT) scans were performed for future reference. (3) CT scan images were processed and drill path was planned to minimize cochlear damage. (4) bi-planar device-assisted drilling was performed on the specimens using the registration. (5) surgical safety was evaluated by calculating the deviation between the drill and the planned paths, and by measuring the closest distance between the drilled path and critical anatomic structures. RESULTS: Eight cases were operated successfully to the basal turn of the cochlear with intact facial nerves (FNs). The deviations from target points and entrance points were 0.86 mm (0.68-1.00 mm) and 0.44 mm (0.30-0.96 mm), respectively. The angular error between the planned and the drilled trajectory was 1.74° (1.26-2.41°). The mean distance from the edge of the drilled path to the FN and to the external canal was 0.60 mm (0.35-0.83 mm) and 1.60 mm (1.30-2.05 mm), respectively. In five specimens, the chorda tympani nerves were well preserved. In all cases, no injury happened to auditory ossicles. CONCLUSIONS: This exploratory study demonstrated the safety of the newly developed image-guided minimally invasive cochlear implantation assisted by the bi-planar device and established the operational procedures. Further, more in vitro experiments are needed to improve the system operation and its safety.

Genetic alteration and misexpression of Polycomb group genes in hepatocellular carcinoma.

Although the abnormal expression of Polycomb-group (PcG) proteins is closely associated with carcinogenesis and the clinicopathological features of hepatocellular carcinoma (HCC), the genetic mutation profile of PcG genes has not been well established. In this study of human HCC specimens, we firstly discovered a highly conserved mutation site, G553C, in the Polycomb Repressive Complex 2 (PRC2) gene enhancer of zeste homolog 2 (EZH2). This site also harbors a single nucleotide polymorphism (SNP), rs2302427, which plays an important antagonistic role in HCC. Kaplan-Meier survival curves showed that the tumor-free and overall survival of patients with EZH2 G553C were superior to those without the mutation. The G allele frequencies in patients and healthy subjects were 0.2% and 0.122%, respectively, with significant differences in distribution. The individuals carrying the GG and the GC genotypes at rs2302427 showed 3.083-fold and 1.827-fold higher risks of HCC, respectively, compared with individuals carrying the wild-type allele. Furthermore, Immunohistochemical staining revealed that the expression levels of CBX8 (in 53/123 samples) and BMI1 (in 60/130 samples) were markedly increased in human HCC specimens. Importantly, the overall and tumor-free survival rates were significantly reduced in the group of patients who simultaneously expressed PRC1 and PRC2. These results argue that a combination of PRC1 and PRC2 expression has a significant predictive/prognostic value for HCC patients. Taken together, our results indicate the abnormal expression and genetic mutation of PcG members are two independent events; cumulative genetic and epigenetic alterations act synergistically in liver carcinogenesis.

Neuropilin 1 expression correlates with the Radio-resistance of human non-small-cell lung cancer cells.

The purpose of this study was to determine the correlation between over-expression of the neuropilin 1 (NRP1) gene and growth, survival, and radio-sensitivity of non-small cell lung carcinoma (NSCLC) cells. 3-[4,5-dimethylthylthiazol-2-yl]-2,5 diphenyltetrazolium broide (MTT) and colony assays were then performed to determine the effect of NRP1 inhibition on the in vitro growth of NSCLC cells. The Annexin V-Fluorescein Isothiocyanate (FITC) apoptosis detection assay was performed to analyse the effect of NRP1 enhancement on apoptosis of NSCLC cells. Transwell invasion and migration assays were employed to examine the metastatic ability of A549 cells post X-ray irradiation. In addition, Western blot assays were carried out to detect the protein level of VEGFR2, PI3K and NF-κB. Finally, to examine the effect of shNRP1 on proliferation and radio-sensitivity in vivo, a subcutaneous tumour formation assay in nude mice was performed. Microvessel density in tumour tissues was assessed by immunohistochemistry. The stable transfected cell line (shNRP1-A549) showed a significant reduction in colony-forming ability and proliferation not only in vitro, but also in vivo. Moreover, shRNA-mediated NRP1 inhibition also significantly enhanced the radio-sensitivity of NSCLC cells both in vitro and in vivo. The over-expression of NRP1 was correlated with growth, survival and radio-resistance of NSCLC cells via the VEGF-PI3K- NF-κB pathway, and NRP1 may be a molecular therapeutic target for gene therapy or radio-sensitization of NSCLC.

The type 2 diabetes mellitus susceptibility gene IGF2BP2 is associated with schizophrenia in a Han Chinese population.

BACKGROUND: Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus, and type 2 diabetes mellitus has shown an association with the rs4402960 gene polymorphism in the insulin-like growth factor II messenger RNA (mRNA)-binding protein 2 gene (IGF2BP2). We tested this polymorphism and mRNA expression levels of IGF2BP2 for an association in Han Chinese patients with schizophrenia compared to healthy controls. METHOD: The rs4402960 polymorphism was genotyped in 790 chronic schizophrenic patients (diagnosed according to DSM-IV) and 1,083 unrelated healthy controls in a case-control design. The IGF2BP2 gene expression levels were assayed in 34 patients with chronic schizophrenia and 30 healthy controls by using real-time polymerase chain reaction (PCR). The study was conducted between 2005 and 2007. RESULTS: We found significant differences in the rs4402960 genotype (χ(2)2 = 7.316, P = .026) and allele (χ(2)1 = 7.056, P = .008) distributions between the patient and control groups. The rs4402960 T allelic frequency was significantly higher in male schizophrenic patients than male controls (28.9% vs 23.5%; P = .004) but not in female patients compared to female controls (27.1% vs 25.5%; P = .498). When real-time PCR was used, the IGF2BP2 gene's isoform B expression levels were significantly greater in schizophrenia than controls (P = .0008). CONCLUSIONS: These results suggest that the IGF2BP2 gene may play a role in susceptibility to schizophrenia, supporting the hypothesis that the co-occurrence of type 2 diabetes mellitus and schizophrenia may be explained by shared genetic risk variants. However, this finding remains preliminary since this association has yet to be replicated.

No association between the type 2 diabetes mellitus susceptibility gene, SLC30A8 and schizophrenia in a Chinese population.

BACKGROUND: The co-occurrence of schizophrenia and type 2 diabetes mellitus (T2DM) has been well documented. Recent genome-wide association studies and meta-analyses have shown robust associations of the solute carrier family 30 member 8 (SLC30A8) gene variants with T2DM in various populations. We examined the involvement of the SLC30A8 in the susceptibility to schizophrenia in a Han Chinese population. METHODS: The SLC30A8 rs13266634 gene polymorphism was genotyped in 837 chronic schizophrenic and 1109 unrelated healthy controls by using a case control design. We also assessed clinical symptoms. RESULTS: There were no significant differences in the rs13266634 genotype (χ(2) = 1.95, df = 2, p = 0.38) and allele (χ(2) = 0.47, df = 1, p = 0.50) distributions between the patient and control groups. There was no association between rs13266634 and clinical symptoms. CONCLUSION: The SLC30A8 gene variation does not appear to contribute a genetic basis for the co-occurrence of schizophrenia and T2DM.

Effect of X-rays on expression of caspase-3 and p53 in EL-4 cells and its biological implications.

OBJECTIVE: To investigate the effect of X-rays on expression of caspase-3 and p53 protein in EL-4 cells and its implications in induction of apoptosis and polyploid cells. METHODS: Mouse lymphoma cell line (EL-4 cells) was used. Fluorescent staining and flow cytometry analysis were employed for measurement of protein expression, apoptosis, cell cycle, and polyploid cells. RESULTS: The expression of caspase-3 protein increased significantly at 8 h and 12 h, compared with that of sham-irradiated control (P<0.05, respectively) and the expression of p53 protein increased significantly at 2, 4, 8, 12, and 24 h, compared with that of sham-irradiated control (P<0.05-P<0.01) in EL-4 cells after 4.0 Gy X-irradiation. Apoptosis of EL-4 cells was increased significantly at 2, 4, 8, 12, 24, 48, and 72 h after 4.0 Gy exposure, compared with that of sham-irradiated control (P<0.05-P<0.001). G2 phase cells were increased significantly at 4, 8, 12, 24, 48, and 72 h (P<0.05-P<0.001). However, no marked change in the number of 8 C polyploid cells was found from 2 to 48 h after 4.0 Gy exposure. CONCLUSION: The expressions of caspase-3 and p53 protein in EL-4 cells are induced by X-rays, which might play an important role in the induction of apoptosis, and the molecular pathway for polyploid formation might be p53-independent.