The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of the TSPO-targeting radioligand [¹⁸F]F-TFQC, an m-trifluoromethyl ER176 analog, in the PET neuroimaging of epileptic rats. Initially, [¹⁸F]F-TFQC was synthesized with a radiochemical yield of 8%-10% (EOS), a radiochemical purity of over 99%, and a specific activity of 38.21 ± 1.73 MBq/nmol (EOS). After determining that [¹⁸F]F-TFQC exhibited good biochemical properties, [¹⁸F]F-TFQC PET neuroimaging was performed in epileptic rats at multiple time points in various stages of disease progression. PET imaging showed specific [¹⁸F]F-TFQC uptake in the right hippocampus (KA-injected site, i.e., epileptogenic zone), which was most pronounced at 1 week (T/NT 1.63 ± 0.21) and 1 month (T/NT 1.66 ± 0.20). The PET results were further validated using autoradiography and pathological analysis. Thus, [¹⁸F]F-TFQC can reflect the TSPO levels and localize the epileptogenic zone, thereby offering the potential for monitoring neuroinflammation and guiding anti-inflammatory treatment in patients with epilepsy.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carrier Proteins/metabolism* ; Cell Line ; Cell Proliferation ; Exosomes/metabolism* ; Lung Neoplasms/genetics* ; Membrane Proteins/metabolism* ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism*

Objective:To investigate the value of three-dimensional (3D) CT in diagnosing cricoarytenoid dislocation.Methods:From January 2021 to December 2021, 31 patients with unilateral cricoarytenoid dislocation who had been treated by reduction forceps at the Affiliated BenQ Hospital of Nanjing Medical University were collected retrospectively, and their voice recovered or improved significantly after therapy. The preoperative CT images were reconstructed by volume rendering (VR). The dislocated side (left and right), type of dislocation (total dislocation and subluxation), and dislocation direction (anterior, posterior, internal and external dislocation) of cricoarytenoid dislocation were observed. According to arytenoid articular surface of cricoid cartilage exposed completely or not (caused by arytenoid displacement), they were divided into complete dislocation and subluxation. According to the direction of arytenoid displacement and the part of arytenoid articular surface of cricoid cartilage exposed, they were divided into anterior, posterior, internal and external dislocation. According to the shape of the vocal cords on laryngoscope, anterior and posterior dislocation of each case was judged, and then compared with that of CT.Results:On VR images, there were 28 cases of cricoarytenoid subluxation (90.3%, 28/31) and 3 cases of complete dislocation (9.7%, 3/31). Left cricoarytenoid dislocation was 26 cases (83.9%, 26/31) and right cricoarytenoid dislocation was 5 cases (16.1%, 5/31). Posterior dislocation was 28 cases (90.3%, 28/31) and anterior dislocation was 3 cases (9.7%, 3/31). There were 23 cases of internal dislocation (74.2%, 23/31), 2 cases of external dislocation (6.4%, 2/31), and 6 cases without obvious internal and external dislocation (19.4%, 6/31). Three cases of complete dislocation were left posterior internal dislocation.There were 24 cases of left posterior dislocation (77.4%, 24/31), 4 cases of right posterior dislocation (12.9%, 4/31), 2 cases of left anterior dislocation (6.4%, 2/31) and 1 case of right anterior dislocation (3.2%, 1/31). On laryngoscope, there were 19 cases of posterior dislocation (61.3%, 19/31), 9 cases of anterior dislocation (29.0%, 9/31), 3 cases were difficult to assess (9.7%, 3/31) because of aryepiglottic fold covering. Sixteen cases (55.2%, 16/28) were consistent with 3D CT, and 12 cases (42.8%, 12/28) were inconsistent.Conclusion:The 3D CT is a reliable method to evaluate cricoarytenoid dislocation, which can show dislocated side, type and direction of cricoarytenoid dislocation clearly.

Objective:To explore whether the specific synaptic vesicle glycoprotein 2A (SV2A) targeted imaging agent ( R)-4-(3-fluoro-5-(fluoro- 18F)phenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidin-2-one ( 18F-SDM-8) can be used to detect epileptic foci. Methods:Twenty male Sprague-Dawley (SD) rats (8-9 weeks) were injected with 1.2 μl of kainic acid (16 rats in the epilepsy group) or saline (4 rats in the control group) into the right hippocampus. 18F-SDM-8 and 18F-FDG mircoPET/CT imaging were respectively performed at 1-2 d (acute phase), 6-7 d (incubation period) and 45-60 d (chronic phase) after the seizure. Asymmetric index (AI) was used to evaluate the epileptic foci identify ability of 18F-SDM-8. Paired t test, Mann-Whitney U test and Pearson correlation analysis were used to analyze data. Results:In the three periods of 18F-SDM-8 imaging, the differences of AI of hippocampus between the epilepsy group and control group were statistically significant ( z values: from -2.64 to 2.67, all P<0.05). Both imaging agents had asymmetric uptake in the epilepsy group (right was lower than left), and the decrease in the medial right temporal lobe was the most significant. The pathological staining results were consistent with the imaging results. In the chronic phase of the epilepsy group, the differences of 18F-SDM-8 SUV mean (right versus left) in each brain area of interest were statistically significant ( t value: from -33.40 to -5.60, all P<0.05). The asymmetric uptake of the two imaging agents in the hippocampus had a better correlation ( r=0.97, P=0.001), and the AI of 18F-SDM-8 ((34.2±8.4)%) in this area was 1.4 times higher than that of 18F-FDG ((24.6±4.7)%). Conclusions:18F-SDM-8 PET is a promising method to test the level of SV2A. It can reflect the changes of SV2A in the rat epilepsy model induced by intrahippocampal injection of kainic acid, and improve the sensitivity of molecular imaging for epileptic foci.

ObjectiveTo explore the brain mechanism of repetitive transcranial magnetic stimulation (rTMS) on dysfunction after stroke using functional magnetic resonance imaging (fMRI). MethodsLiteratures about the functional magnetic resonance imaging study about repetitive transcranial magnetic stimulation for dysfunction after stroke were retrieved in PubMed, Web of Science, CNKI and Wanfang data from establishment to June 1st, 2021. The quality of the literature was evaluated with Physiotherapy Evidence Database (PEDro) scale. Literature screening, and data extraction were performed by two researchers. ResultsA total of 14 randomized controlled trials were finally enrolled. They were of high or very high quality. They mainly involved the therapeutic effect and imaging mechanisms of rTMS on dysfunction after stroke. ConclusionrTMS could change the excitability of the cerebral cortex and the effective connections between brain regions after stroke, promote the reorganization of brain function, and achieve the recovery of post-stroke dysfunction.

Objective:To investigate the clinical effectiveness of one-stage biplanar osteotomy correction of angulation and shortening deformity of the lower extremity after epiphyseal injury of the distal femur with a monorail external fixator.Methods:The data of 5 patients (2 males and 3 females) with angulation and shortening deformity in the lower extremity after epiphyseal injury of the distal femur were retrospectively analyzed.The patients underwent monorail external fixator assisted one-stage osteotomy correction of the distal femur and distraction osteogenesis of the middle and upper femur in Zhengzhou Orthopeadics Hospital from May 2017 to December 2019.The mean age was 13.6 years old (range: 10 to 17 years old). The affected limbs were shortened by 5.1 cm on average (range: 3.9 to 6.5 cm). The average angulation deformity of the distal femur was 24.9° (range: 17.0°to 30.5°). The mechanical lateral distal femoral angle (mLDFA), the mechanical posterior distal femoral angle (mPDFA), the mechanical axis deviation (MAD), the range of motion (ROM) of the knee, and the length of the lower limbs before surgery and at the final follow-up were measured and analyzed.Results:All patients were followed up for 22 months on average (range: 15 to 32 months). For all the 5 patients, the mechanical axis was well realigned, mLDFA, mPDFA, and MAD returned to normal range, and the length of the affected limb achieved the goal as planned before the surgery.Besides, the affected limbs were lengthened by 5.6 cm on average (range: 3.9 to 8.0 cm), and the median healing index was 35.6 d/cm (range: 29.0 to 45.0 d/cm). The bone callus in the distraction area and the osteotomy end were well healed at the final follow-up, as indicated by the X-ray results.At the end of the distraction period, the flexion ROM of the knee in all patients reached basically 90°.By the final follow-up, all patients had a normal knee ROM.No vascular or nerve injury, dislocation of hips or knee joints, re-fracture after disassembly, deep infection and other complications were observed in all patients.Conclusions:One-stage biplanar osteotomy correction of angulation and shortening deformity of the lower extremity after epiphyseal injury of the distal femur with a monorail external fixator is safe and feasible.The method requires no multiple operations and improves the tolerance of patients during the treatment period.

ObjectiveTo evaluate the efficacy and safety of rifaximin in the prevention of spontaneous bacterial peritonitis (SBP). MethodsCNKI, Wanfang Data, CBM, PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) and cohort studies on rifaximin in the prevention of SBP published up to July 5, 2020. The articles were screened according to the inclusion and exclusion criteria, and data extraction and quality assessment were performed. RevMan 5.3 software was used to conduct the meta-analysis. Results A total of 13 studies (with 2207 patients in total) were included, among which there were 6 RCTs and 7 cohort studies. The results of the meta-analysis showed that compared with the non-prevention group, the rifaximin group had significantly lower incidence rate of SBP (odds ratio ［OR］=0.36, 95% confidence interval ［CI］: 0.14-0.96, P=0.04) and mortality rate (OR=0.59, 95% CI: 037-0.95, P=0.03); compared with the norfloxacin group, the rifaximin group had significantly lower incidence rate of SBP (OR=039, 95% CI: 025-0.62, P＜0.001), mortality rate (OR=0.55, 95% CI: 0.34-0.92, P=0.02), and adverse reactions (OR=0.36, 95% CI: 0.22-059, P＜0.001). The subgroup analysis based on the type of prevention showed that there was no significant difference in primary prevention between the two groups (OR=0.56, 95% CI: 0.23-1.35, P=0.20), and in secondary prevention, the rifaximin group had a significantly lower incidence rate of SBP (OR=0.18, 95% CI: 0.08-0.43, P＜0.001). In addition, it was also found that rifaximin significantly reduced the incidence rate of hepatorenal syndrome (OR=0.34, 95% CI: 0.15-0.77, P=0.01) and hepatic encephalopathy (OR=0.55, 95% CI: 0.32-0.95, P=0.03). ConclusionRifaximin is safe and effective for the primary and secondary prevention of SBP. Rifaximin is superior to norfloxacin in secondary prevention, which still needs to be confirmed by high-quality multicenter RCTs.

Objective: To compare the efficacy of core decompression with autologous bone marrow mononuclear cell grafting with impacted bone grafting in treating bilateral femoral head necrosis. Methods: From January 2011 to January 2017, a total of 44 patients with bilateral femoral head necrosis (88 hips) were admitted to the Department of Orthopaedics, China-Japan Friendship Hospital, including 35 males and 9 females with aged 34.9±7.2 years old (ranged from 22-48 years). Core decompression with autologous bone marrow mononuclear cell and impacted bone grafting were conducted to each hip joint for every patient. All patients were followed up for every 3 months at the first year postoperatively and for every 6 months thereafter. The following clinical measurement were recorded, Harris hip score (HHS), visual analogue score (VAS), the anterior-posterior and frog lateral radiographs, and CT. The 5-year survival rate of the hip was calculated with the endpoint event being defined as a need for total hip arthroplasty or other surgical intervention, or a HHS less than 70. Results: The postoperative follow-up duration was 50.5±34.2 months in the impacted bone grafting group and 54.0±33.1 months in the core decompression with autologous bone marrow mononuclear cells group. Fifteen hips in the impacted bone grafting group and 13 hips in the core decompression with autologous bone marrow mononuclear cell group failed during the follow-up. The 5-year cumulative survival rates of the hips in two groups were 64.7% and 72.1%, respectively [HR=1.178, 95%CI(0.561, 2.477)]. In the impacted bone grafting group, the 5-year survival rates of the hip joints at the ARCO IIIB+IIIC and IIIA stages were 42.9% and 74.2%, respectively [HR=3.258, 95%CI(1.172, 9.059)]. In the core decompression with autologous bone marrow mononuclear cell group, the 5-year survival rates of hips at the ARCO stage I, II and IIIA stages were 50.0%, 75.3%, and 71.4%, respectively (χ²=0.757, P=0.685). Age, gender, BMI, preoperative HHS and etiology did not affect the effects of core decompression with autologous bone marrow mononuclear cell grafting or impacted bone grafting (P>0.05). The preoperative VAS of the impacted bone grafting group and the core decompression with autologous bone marrow mononuclear cell grafting group were 4.80±0.62 and 3.27±1.17, respectively (t=8.625, P<0.001). At the last follow-up, the VAS was reduced to 2.84±1.95 and 2.25±2.08, respectively (t=2.712, P=0.01; t=7.087, P<0.001) with significant difference in postoperative VAS between the two groups (t=2.489, P=0.017). The preoperative HHS of the impacted bone grafting group and the core decompression with autologous bone marrow mononuclear cell grafting group were 77.02±5.03 and 82.57±5.71, respectively (t=7.822, P<0.001). At the last follow-up, the HHS increased to 81.57±12.81 and 83.55±12.87, respectively. The difference between the preoperative and postoperative HHS was statistically significant in the impacted bone grafting group (t=2.389, P=0.021) but not in the core decompression with autologous bone marrow mononuclear cell grafting group (t=0.451, P=0.654). There was no significant difference in postoperative HHS between the two groups (t=1.353, P=0.183). Conclusion Both impacted bone grafting and core decompression with autologous bone marrow mononuclear cell grafting are safe and effective methods in treating femoral head necrosis. The ARCO stage is a risk factor affecting the prognosis of hips after impacted bone grafting, which has no effect on the mid-term survival of hips after core decompression with autologous bone marrow mononuclear cell grafting.