Rich-silicon rice husk ash increases iron plaque formation and decreases cadmium and arsenic accumulation in rice seedlings.

Combined Cd (cadmium) and As (arsenic) pollution in cultivated land affects the safety of crops production and endangers human health. Rice (Oryza sativa L.) is a crop that uptakes Si (silicon), and Si can effectively promote rice growth and mitigate heavy metal toxicity. This study examined the effect and mechanism of Si-rich amendment (HA) prepared by aerobic combustion of rice husk on Cd and As accumulation in iron plaque and rice seedlings via hydroponic experiments. HA enhanced the vitality of rice growth because of its Si content and increased the amount of amorphous fraction iron plaques, furthermore, Cd content was decreased while the As was increased in both amorphous fraction and crystalline fraction iron plaques, resulting in the contents of Cd and As decreases by 10.0%-38.3% and 9.6%-42.8% for the shoots, and by 13.4%-45.2% and 9.9%-20.0% for the roots, respectively. In addition, X-ray diffraction and X-ray photoelectron spectroscopy illustrated significantly more Fe2O, MnO2 and MnO in the iron plaque after HA supply and the simultaneous existence of Mn-As and Mn-Si compounds. This result revealed less Cd from iron plaque and more As retention with HA supply, reducing the amount of Cd and As up taking and accumulation by rice seedlings. HA is beneficial to rice growth and reduce the absorption of heavy metals in plants. At the same time, HA is environmentally friendly, it can be used for the remediation of paddy fields contaminated by Cd and As.

Single-Atom Iron Doped Carbon Dots with Highly Efficient Electrochemiluminescence for Ultrasensitive Detection of MicroRNAs.

Herein, single-atom iron doped carbon dots (SA Fe-CDs) were successfully prepared as novel electrochemiluminescence (ECL) emitters with high ECL efficiency, and a biosensor was constructed to ultrasensitively detect microRNA-222 (miRNA-222). Importantly, compared with the conventional without single-atom doped CDs with low ECL efficiency, SA Fe-CDs exhibited strong ECL efficiency, in which single-atom iron as an advanced coreactant accelerator could significantly enhance the generation of reactive oxygen species (ROS) from the coreactant S2O82- for improving the ECL efficiency. Moreover, a neoteric amplification strategy combining the improved strand displacement amplification with Nt.BbvCI enzyme-induced target amplification (ISDA-EITA) could produce 4 output DNAs in every cycle, which greatly improved the amplification efficiency. Thus, a useful ECL biosensor was built with a detection limit of 16.60 aM in the range of 100 aM to 1 nM for detecting traces of miRNA-222. In addition, miRNA-222 in cancer cell lysate (MHCC-97L) was successfully detected by using the ECL biosensor. Therefore, this strategy provides highly efficient single-atom doped ECL emitters for the construction of sensitive ECL biosensing platforms in the biological field and clinical diagnosis.

Application and progress of nanozymes in antitumor therapy.

Tumors remain one of the major threats to public health and there is an urgent need to design new pharmaceutical agents for their diagnosis and treatment. In recent years, due to the rapid development of nanotechnology, biotechnology, catalytic science, and theoretical computing, subtlety has gradually made great progress in research related to tumor diagnosis and treatment. Compared to conventional drugs, enzymes can improve drug distribution and enhance drug enrichment at the tumor site, thereby reducing drug side effects and enhancing drug efficacy. Nanozymes can also be used as tumor tracking imaging agents to reshape the tumor microenvironment, providing a versatile platform for the diagnosis and treatment of malignancies. In this paper, we review the current status of research on enzymes in oncology and analyze novel oncology therapeutic approaches and related mechanisms. To date, a large number of nanomaterials, such as noble metal nanomaterials, nonmetallic nanomaterials, and carbon-based nanomaterials, have been shown to be able to function like natural enzymes, particularly with significant advantages in tumor therapy. In light of this, the authors in this review have systematically summarized and evaluated the construction, enzymatic activity, and their characteristics of nanozymes with respect to current modalities of tumor treatment. In addition, the application and research progress of different types of nicknames and their features in recent years are summarized in detail. We conclude with a summary and outlook on the study of nanozymes in tumor diagnosis and treatment. It is hoped that this review will inspire researchers in the fields of nanotechnology, chemistry, biology, materials science and theoretical computing, and contribute to the development of nano-enzymology.

Long-term effects of compound passivator coupled with silicon fertilizer on the reduction of cadmium and arsenic accumulation in rice and health risk evaluation.

Cadmium (Cd) and arsenic (As) are precedence-controlled contaminants in paddy soils, that can easily accumulate in rice grains. Limestone and sepiolite (LS) compound passivator can obviously reduce Cd uptake in rice, whereas Si fertilizer can effectively decrease rice As uptake. Here, the synergistic effects of the LS compound passivator coupled with Si fertilizer (LSCS) on the soil pH and availability of Si, Cd, and As, as well as rice grain Cd and As accumulation and its health risk were studied based on a 3-year consecutive field experiment. The results showed that the LSCS performed the best in terms of synchronously decreasing soil Cd and As availability and rice Cd and As uptake. In the LSCS treatments, soil pH gradually decreased with the rice-planting season, while soil available Cd and As contents gradually increased, suggesting that the influence of LSCS on Cd and As availability gradually weakened with rice cultivation. Nonetheless, the contents of Cd and inorganic As (i-As) in rice grains treated with LSCS were slightly affected by cultivation but were significantly lower than the single treatments of LS compound passivator or Si fertilizer. According to the Cd and As limit standards in food (GB2762-2022), the Cd and i-As content in rice grains can be lowered below the standard by using the 4500 kg/hm2 LS compound passivator coupled with 90 kg/hm2 Si fertilizer in soil and spraying 0.4 g/L Si fertilizer on rice leaves for at least three years. Furthermore, health risk evaluation revealed that LSCS treatments significantly reduced the estimated daily intake, annual excess lifetime cancer risk, and hazard quotient of Cd and i-As in rice grains. These findings suggest that LSCS could be a viable approach for reducing Cd and As accumulation in rice grains and lowering the potential health risks associated with rice.

Fluorescence Imaging of Diabetic Cataract-Associated Lipid Droplets in Living Cells and Patient-Derived Tissues.

Diabetic cataract (DC) surgery carries risks such as slow wound healing, macular edema, and progression of retinopathy and is faced with a deficiency of effective drugs. In this context, we proposed a protocol to evaluate the drug's efficacy using lipid droplets (LDs) as the marker. For this purpose, a fluorescent probe PTZ-LD for LDs detection is developed based on the phenothiazine unit. The probe displays polarity-dependent emission variations, i.e., lower polarity leading to stronger intensity. Especially, the probe exhibits photostability superior to that of Nile Red, a commercial LDs staining dye. Using the probe, the formation of LDs in DC-modeled human lens epithelial (HLE) cells is validated, and the interplay of LDs-LDs and LDs-others are investigated. Unexpectedly, lipid transfer between LDs is visualized. Moreover, the therapeutic efficacy of various drugs in DC-modeled HLE cells is assessed. Ultimately, more LDs were found in lens epithelial tissues from DC patients than in cataract tissues for the first time. We anticipate that this work can attract more attention to the important roles of LDs during DC progression.

Low-Intensity Focused Ultrasound Alleviates Chronic Neuropathic Pain-Induced Allodynia by Inhibiting Neuroplasticity in the Anterior Cingulate Cortex.

Low-intensity focused ultrasound (LIFU) is a potential noninvasive method to alleviate allodynia by modulating the central nervous system. However, the underlying analgesic mechanisms remain unexplored. Here, we assessed how LIFU at the anterior cingulate cortex (ACC) affects behavior response and central plasticity resulting from chronic constrictive injury (CCI). The safety of LIFU stimulation was assessed by hematoxylin and eosin (H&E) and Fluoro-Jade C (FJC) staining. A 21-day ultrasound exposure therapy was conducted from day 91 after CCI surgery in mice. We assessed the 50% mechanical withdrawal threshold (MWT50) using Von Frey filaments (VFFs). The expression levels of microtubule-associated protein 2 (MAP2), growth-associated protein 43 (GAP43), and tau were determined via western blotting (WB) and immunofluorescence (IF) staining to evaluate the central plasticity in ACC. The regions of ACC were activated effectively and safely by LIFU stimulation, which significantly increased the number of c-fos-positive cells (P < 0.05) with no bleeding, coagulative necrosis, and neuronal loss. Under chronic neuropathic pain- (CNP-) induced allodynia, MWT50 decreased significantly (P < 0.05), and overexpression of MAP2, GAP43, and tau was also observed. After 3 weeks of treatment, significant increases in MWT50 were found in the CCI+LIFU group compared with the CCI group (P < 0.05). WB and IF staining both demonstrated a significant reduction in the expression levels of MAP2, GAP43, and tau (P < 0.05). LIFU treatment on ACC can effectively attenuate CNP-evoked mechanical sensitivity to pain and reverse aberrant central plasticity.

CT-based radiomics nomogram may predict local recurrence-free survival in esophageal cancer patients receiving definitive chemoradiation or radiotherapy: A multicenter study.

BACKGROUND AND PURPOSE: To establish and validate a contrast-enhanced computed tomography-based hybrid radiomics nomogram for prediction of local recurrence-free survival (LRFS) in esophageal squamous cell cancer (ESCC) patients receiving definitive (chemo)radiotherapy in a multicenter setting. MATERIALS AND METHODS: This retrospective study included 302 ESCC patients from Xijing Hospital receiving definitive (chemo)radiotherapy, which were randomly assigned to the training (n = 201) and internal validation sets (n = 101). And 74 and 21 ESCC patients from the other two centers were used as the external validation set (n = 95). A hybrid radiomics nomogram was established by integrating clinical factors, radiomic signature and deep-learning signature in training set and was tested in two validation sets. RESULTS: The deep-learning signature showed better prognostic performance than radiomic signature for predicting LRFS in training (C-index: 0.73 vs 0.70), internal (Cindex: 0.72 vs 0.64) and external validation sets (C-index: 0.72 vs 0.63), which could stratify patients into high and low-risk group with different prognosis (cut-off value: -0.06). Low-risk groups had better LRFS than high-risk groups in training (p < 0.0001; 2-y LRFS 71.1% vs 33.0%), internal (p < 0.01; 2-y LRFS 58.8% vs 34.8%) and external validation sets (p < 0.0001; 2-y LRFS 61.9% vs 22.4%), respectively. The hybrid radiomics nomogram established by integrating radiomic signature, deep-learning signature with clinical factors including T stage and concurrent chemotherapy outperformed any one or two combinations in training (C-index: 0.82), internal (Cindex: 0.78), and external validation sets (C-index: 0.76). Calibration curves showed good agreement. CONCLUSIONS: The hybrid radiomics based on pretreatment contrast-enhanced computed tomography provided a promising way to predict local recurrence of ESCC patients receiving definitive (chemo)radiotherapy.

Classification of unilateral cervical locked facet with or without lateral mass-facet fractures and a retrospective observational study of 55 cases.

This study describes a morphology-based unilateral cervical facet interlocking classification in an attempt to clarify the injury mechanism, instability, neurological deficits, radiological features, and determine optimum management strategies for these injuries. A total of 55 patients with unilateral cervical locked facet (UCLF) involving C3 to C7 were identified between January 1, 2012 and December 1, 2019. The injuries were classified into three types, and they were further divided into six subtypes using three-dimensional computed tomography. The injury mechanism, clinical features, neurological deficits, and imaging characteristics were analyzed, and the appropriate treatment strategies for UCLF were discussed. UCLFs were divided into the following six subtypes: UCLF without lateral mass-facet fracture (type I) in nine cases, with superior articular process fracture (type II A) in 22, with inferior articular process fracture (type II B) in seven, both superior and inferior articular process fractures (type II C) in four, with lateral mass splitting fracture (type III A) in three, and with lateral mass comminution fractures (type III B) in ten. A total of 22 (40.0%) of the 55 patients presented with radiculopathy, and 23 patients (41.8%) had spinal cord injuries. The subtype analyses showed high rates of radiculopathy in types II A (68.2%) and II C (75.0%), as well as significant spinal cord injury in types I (77.8%) and III (61.5%). Destruction of the facet capsule was observed in all patients, but the injury of disc, ligamentous complex, and vertebra had a significant difference among the types or subtypes. The instability parameters of the axial rotation angle, segmental kyphosis, and sagittal displacement showed significant differences in various types of UCLF. Closed reduction by preoperative and intraoperative general anesthesia traction was achieved in 27 patients (49.1%), and successful rate of closed reduction in type I (22.2%) was significantly lower than that in type II (51.5%) and type III (61.5%). A total of 35 of 55 patients underwent a single anterior fixation and fusion, 10 patients were treated with posterior pedicle and (or) lateral mass fixation, and combined surgery was performed in ten patients. Ten patients (18.2%) with a poor outcome were observed after first surgery. Among them, 3 patients treated with a single anterior surgery had persistent or aggravated radiculopathy and posterior approach surgery with ipsilateral facet resection, foramen enlargement, and pedicle and (or) lateral mass screw fixation was performed immediately, 5 patients treated with a short-segment posterior surgery showed mild late kyphosis deformity, and 2 patients with vertebral malalignment were encountered after anterior single-level fusion during the follow-up. This retrospective study indicated that UCLF is a rotationally unstable cervical spine injury. The classification proposed in this study will contribute to understanding the injury mechanism, radiological characteristics, and neurological deficits in various types of UCLF, which will help the surgeons to evaluate the preoperative closed reduction and guide the selection of surgical approach and fusion segment.

LIFU Alleviates Neuropathic Pain by Improving the KCC2 Expression and Inhibiting the CaMKIV-KCC2 Pathway in the L4-L5 Section of the Spinal Cord.

Effective treatment remains lacking for neuropathic pain (NP), a type of intractable pain. Low-intensity focused ultrasound (LIFU), a noninvasive, cutting-edge neuromodulation technique, can effectively enhance inhibition of the central nervous system (CNS) and reduce neuronal excitability. We investigated the effect of LIFU on NP and on the expression of potassium chloride cotransporter 2 (KCC2) in the spinal cords of rats with peripheral nerve injury (PNI) in the lumbar 4-lumbar 5 (L4-L5) section. In this study, rats received PNI surgery on their right lower legs followed by LIFU stimulation of the L4-L5 section of the spinal cord for 4 weeks, starting 3 days after surgery. We used the 50% paw withdraw threshold (PWT50) to evaluate mechanical allodynia. Western blotting (WB) and immunofluorescence (IF) were used to calculate the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB), and KCC2 in the L4-L5 portion of the spinal cord after the last behavioral tests. We found that PWT50 decreased (P < 0.05) 3 days post-PNI surgery in the LIFU- and LIFU+ groups and increased (P < 0.05) after 4 weeks of LIFU stimulation. The expression of p-CREB and CaMKIV decreased (P < 0.05) and that of KCC2 increased (P < 0.05) after 4 weeks of LIFU stimulation, but that of p-ERK1/2 (P > 0.05) was unaffected. Our study showed that LIFU could effectively alleviate NP behavior in rats with PNI by increasing the expression of KCC2 on spinal dorsal corner neurons. A possible explanation is that LIFU could inhibit the activation of the CaMKIV-KCC2 pathway.

Advances in The Diagnosis and Treatment of Achalasia of The Cardia: a Review.

Idiopathic achalasia is an esophageal motor disorder characterized by the loss of the lower esophageal sphincter ganglion, resulting in impaired lower esophageal relaxation and absence of esophageal peristalsis. Patients commonly present with progressive dysphagia accompanied by reflux, heartburn, retrosternal pain, and severe weight loss. Diagnosis is primarily based on the patient's chief complaints, barium esophagography, and the most recent high-resolution manometry. Endoscopic assessment and endoscopic ultrasonography also have significant value with regard to the exclusion of esophageal anatomical lesions, neoplastic diseases, and pseudoachalasia. However, as most patients with achalasia demonstrate a gradual onset, early diagnosis is difficult. Currently, treatment of idiopathic achalasia, including pneumatic dilation, stent placement, and surgical myotomy, is aimed at reducing lower esophageal sphincter pressure and relieving the symptoms of dysphagia. Peroral endoscopic myotomy has gradually become the mainstream treatment because it causes less trauma and has a rapid recovery rate. This article reviews the main methods of diagnosis and treatment of achalasia, with an emphasis on the potential of peroral endoscopic myotomy and the advancements of immunotherapy for achalasia.

Stent placement to prevent strictures after esophageal endoscopic submucosal dissection: a systematic review and meta-analysis.

Endoscopic submucosal dissection (ESD) is an important method for the treatment of early esophageal cancer. However, post-procedure stenosis is one of the most common long-term complications. This meta-analysis aimed to investigate whether stent placement is effective in the stenosis prevention, and which type of stent would be more effective. A systematic and electronic search of clinical trials and observational studies conducted before March 2020 on the efficacy of stent placement in preventing esophageal stricture after ESD was performed. Search terms included "ESD," "esophageal stenosis," "esophageal stricture," and "stents." We conducted a bias risk assessment of the eligible reports and a meta-analysis of the data using Revman 5.3 software. We included two randomized controlled trials (RCTs) and a prospective cohort study involving 163 patients with esophageal mucosal defects encompassing at least three-quarters of the esophagus circumference after ESD. The meta-analysis results showed that post-ESD stenosis rates (RR, 0.37; 95% CI, 0.22-0.64; P = 0.0003) and the number of endoscopic balloon dilations (EBDs) (MD, -1.74; 95% CI, -2.46 to -1.01; P < 0.00001) were reduced in the pooled analysis of three studies, indicating that stent placement was effective for stenosis prevention, especially a polyglycolic acid (PGA) sheet combined with stent placement can prevent stenosis (RR, 0.41; 95% CI, 0.23-0.74; P = 0.003) and reduce the number of EBDs (MD, -1.65; 95% CI, -2.40 to -0.90; P < 0.0001) significantly. Stent placement can reduce the rate of esophageal stenosis after ESD, especially when stents are covered with PGA sheets. However, more high-quality, low-bias RCTs with a sufficient sample size are needed to demonstrate its effectiveness.

Endoscopic full-thickness resection using an over-the-scope device: A prospective study.

BACKGROUND: Endoscopic submucosal dissection to treat mucosal and submucosal lesions sometimes results in low rates of microscopically margin-negative (R0) resection. Endoscopic full-thickness resection (EFTR) has a high R0 resection rate and allows for the definitive diagnosis and treatment of selected mucosal and submucosal lesions that are not suitable for conventional resection techniques. AIM: To evaluate the efficacy and safety of EFTR using an over-the-scope clip (OTSC). METHODS: This prospective, single-center, non-randomized clinical trial was conducted at the endoscopy center of Shengjing Hospital of China Medical University. The study included patients aged 18-70 years who had gastric or colorectal submucosal tumors (SMTs) (≤ 20 mm in diameter) originating from the muscularis propria based on endoscopic ultrasound (EUS) and patients who had early-stage gastric or colorectal cancer (≤ 20 mm in diameter) based on EUS and computed tomography. All lesions were treated by EFTR combined with an OTSC for wound closure between November 2014 and October 2016. We analyzed patient demographics, lesion features, histopathological diagnoses, R0 resection (negative margins) status, adverse events, and follow-up results. RESULTS: A total of 68 patients (17 men and 51 women) with an average age of 52.0 ± 10.5 years (32-71 years) were enrolled in this study, which included 66 gastric or colorectal SMTs and 2 early-stage colorectal cancers. The mean tumor diameter was 12.6 ± 4.3 mm. The EFTR procedure was successful in all cases. The mean EFTR procedure time was 39.6 ± 38.0 min. The mean OTSC defect closure time was 5.0 ± 3.8 min, and the success rate of closure for defects was 100%. Histologically complete resection (R0) was achieved in 67 (98.5%) patients. Procedure-related adverse events were observed in 11 (16.2%) patients. The average post-procedure length of follow-up was 48.2 ± 15.7 mo. There was no recurrence during follow-up. CONCLUSION: EFTR combined with an OTSC is an effective and safe technique for the removal of select subepithelial and epithelial lesions that are not amenable to conventional endoscopic resection techniques.

Endoscopic fenestration in the diagnosis and treatment of delayed anastomotic submucosal abscess: A case report and review of literature.

BACKGROUND: Abscess formation is one of the complications after radical resection of rectal cancer; cases with delayed postoperative anastomotic abscess are rare. Here, we report a rare case of postoperative anastomotic abscess with a submucosal neoplasm appearing after rectal surgery. Ultimately, the patient was diagnosed and treated by endoscopic fenestration. In addition, we review the literature on the appearance of an abscess as a complication after rectal cancer surgery. CASE SUMMARY: A 57-year-old man with a history of rectal malignancy resection complained of a smooth protuberance near the anastomotic stoma. Endoscopic ultrasonography revealed a hypoechoic structure originating from the muscularis propria, and a submucosal tumor was suspected. The patient was subsequently referred to our hospital and underwent pelvic contrast-enhanced computed tomography, which revealed no thickening or strengthening of the anastomotic wall. In order to clarify the origin of the lesion and obtain the pathology, endoscopic fenestration was performed. After endoscopic procedure, a definitive diagnosis of delayed anastomotic submucosal abscess was established. The patient achieved good recovery and prognosis after the complete clearance of abscess. CONCLUSION: Endoscopic fenestration may be safe and effective for the diagnosis/treatment of delayed intestinal smooth protuberance after rectal cancer surgery.

Endoscopic ultrasound-measured muscular thickness of the lower esophageal sphincter and long-term prognosis after peroral endoscopic myotomy for achalasia.

BACKGROUND: People with achalasia typically have a thick lower esophageal muscularis propria (LEMP), and peroral endoscopic myotomy (POEM) has been effective in treating most patients. LEMP thickness may be associated with the outcomes and prognosis after POEM. However, more evidence is needed regarding the relationship between LEMP thickness and patient prognosis after POEM. AIM: To assess the association between LEMP thickness, measured using endoscopic ultrasound (EUS), and long-term prognosis, especially relapse, after POEM for achalasia. METHODS: All medical records, including EUS data, of patients who underwent POEM to treat achalasia at Shengjing Hospital of China Medical University from January 2012 to September 2018 were retrospectively reviewed. LEMP thickness was measured by EUS, and a thickness of ≥ 3 mm was defined as thickened. The severity of patient symptoms was evaluated using the Eckardt score. Relapse was defined as a 3-point rise in the Eckardt score after a period of clinical remission. The relationship between patient characteristics, muscle thickness, and recurrence was analyzed. RESULTS: Eighty-two patients (32 males and 50 females, aged 17-78 years) and 85 POEM procedures were included. In total, 76.8% (63/82 patients) of patients had a thickened muscularis propria. Older age and longer disease course were associated with muscularis propria thickening (P < 0.05). The mean postoperative follow-up time was 35.4 ± 17.2 mo (range, 8-87.5 mo) in 60 patients. Five patients with Eckardt scores > 3 refused further management after their symptoms were relieved. The relapse rate was 12.73% (7/55 cases). Five patients, four of whom had muscularis propria thickening, had disease recurrence within 12 mo after the procedure. Achalasia relapsed in one patient who had a thickened muscularis propria after 24 mo and in another patient who did not have a thickened muscularis propria after 30 mo. Patients with recurrence were typically younger and had a shorter disease course (P < 0.05). The relapse rate in patients with a non-thickened muscularis propria tended to be higher (18.2%, 2/11 patients) than that in patients with a thickened muscularis propria (11.4%, 5/44 patients), although no significant difference was found. Age (hazard ratio = 0.92; 95% confidence interval: 0.865-0.979; P < 0.05) and being male (hazard ratio = 7.173; 95% confidence interval: 1.277-40.286; P < 0.05) were identified as risk factors for symptomatic recurrence by multivariable analysis using the Cox model. CONCLUSION: Patients with a thickened muscularis are typically older and have a longer disease course. Younger age and the male sex are associated with increased recurrence. Patients with a thin muscularis propria may be prone to relapse, although further validation is needed.

Advances in the Prevention and Treatment of Esophageal Stricture after Endoscopic Submucosal Dissection of Early Esophageal Cancer.

Endoscopic submucosal dissection (ESD) has become the main treatment for early esophageal cancer. While treating the disease, ESD may also cause postoperative esophageal stricture, which is a global issue that needs resolution. Various methods have been applied to resolve the problem, such as mechanical dilatation, glucocorticoids, anti-scarring drugs, and regenerative medicine; however, no standard treatment regimen exists. This article describes and evaluates the strengths and limitations of new and promising potential strategies for the treatment and prevention of esophageal strictures.

Comparison of endoscopic ultrasound-guided hepaticogastrostomy and the antegrade technique in the management of unresectable malignant biliary obstruction: study protocol for a prospective, multicentre, randomised controlled trial.

BACKGROUND: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is used after failed endoscopic retrograde cholangiopancreatography. Based on existing studies, intrahepatic (IH) approaches are preferred in patients with dilated IH bile ducts. Both ultrasound-guided hepaticogastrostomy (EUS-HGS) and ultrasound-guided antegrade treatment (EUS-AG) are appropriate for patients with unreachable papillae. Nevertheless, there have been no direct comparisons between these two approaches. Therefore, we aim to evaluate and compare the safety and efficiency of EUS-HGS and EUS-AG in patients with an unreachable papilla. METHODS: This is a prospective, randomised, controlled, multicentre study with two parallel groups without masking. One hundred forty-eight patients from three hospitals who met the inclusion criteria will be randomly assigned (1:1) to undergo either EUS-HGS or EUS-AG for relief of malignant biliary obstruction. The final study follow-up is scheduled at 1 year postoperatively. The primary endpoint is efficiency, described by technical and clinical success rates of EUS-HGS and EUS-AG in patients with unreachable papillae. The secondary endpoints include stent patency, overall survival rates, complication rates, length of hospital stays, and hospitalisation expenses. The chi-square test, Kaplan-Meier methods, log-rank test, and Cox regression analysis will be used to analyse the data. DISCUSSION: To our knowledge, this is the first study to compare these two EUS-BD approaches directly using a multicentre, randomised, controlled trial design. The clinical economic indexes will also be compared, as they may also affect the patient's choice. The result may contribute to establishing a strategic guideline for choosing IH EUS-BD approaches. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR1900020737 . Registered on 15 January 2019.

Is it Suitable to Fix the Occipito-C2 Angle and the Posterior Occipitocervical Angle in a Normal Range During Occipitocervical Fusion?

STUDY DESIGN: This is a retrospective study. OBJECTIVES: The objective of this study was (1) to measure the occipito-C2 angle (OC2A) and the posterior occipitocervical angle (POCA) in a normal population, and (2) to observe the effects of OC2A and POCA selection on postoperative clinical efficacy and lower cervical curvature after occipitocervical fusion (OCF) in patients with basilar invagination (BI) and atlantoaxial fracture and dislocation (AAFD). SUMMARY OF BACKGROUND DATA: OC2A has received special attention with respect to the clinical efficacy during OCF. However, none of studies have focused on the relationship between OC2A and POCA and have assessed their impact on clinical outcomes in patients with different occipiocervical diseases. MATERIALS AND METHODS: One hundred fifty healthy subjects without any cervical disease (healthy group) were randomly selected based on sex and age. Three spine surgeons measured the OC2A and POCA in the healthy group and averaged the values. Forty-two patients with BI (BI group) and 32 patients with AAFD (AAFD group) who underwent OCF between January 2012 and January 2017 were reviewed. OC2A, POCA, and cervical spinal angle (CSA) were measured preoperatively, postoperatively immediately after surgery and ambulation, and at the final follow-up visit. The preoperative and final follow-up visual analog scale (VAS), Japanese Orthopaedic Association score (JOA), neck disability index (NDI), and the change of CSA from postoperatively immediately after surgery and ambulation to the final follow-up (dCSA) were recorded. RESULTS: The values of OC2A and POCA were 14.5±3.7 and 108.2±8.1 degrees in the healthy group, respectively, and the respective 95% confidence intervals were 7.2-21.8 and 92.3-124.0 degrees as the normal range. There was a negative correlation between OC2A and POCA (r=-0.386, P<0.001). The preoperative value of OC2A (5.6±4.3 degrees) in BI group was smaller than that in the healthy group (P<0.05); however, the preoperative value of POCA (123.0±10.4 degrees) in the BI group was larger than that in the healthy group (P<0.05). There was no significantly different of OC2A and POCA between the healthy group and the AAFD group before the operation (P>0.05). The preoperative value of CSA (25.7±9.5 degrees) in the BI group was larger than that in the AAFD group (16.5±5.1 degrees) (P<0.05). In the BI group, 26 patients had ideal OC2A and POCA (both within 95% confidence interval of the healthy group) postoperatively immediately after surgery and ambulation as a subgroup of the ideal angle group. In the remaining patients with BI (nonideal angle group), VAS, JOA, and NDI at the final follow-up were significantly better than those in the ideal angle group (P<0.05). The ideal angle group showed statistically greater dCSA than the nonideal angle group of the BI group (P<0.05). On the contrary, in the AAFD group, the NDI in the ideal angle group (20 patients) was better than that in the nonideal angle group at the final follow-up, and the ideal angle group had a smaller dCSA compared with the nonideal angle group (P<0.05). CONCLUSIONS: The biomechanical balance of occipitocervical region in patients with occipitocervical diseases with different pathogenesis is different. On the basis of the different types of occipitocervical diseases, an appropriate range of OC2A and POCA should be selected by the surgeon during OCF, which can further improve the clinical efficacy and reduce the loss of the lower cervical curvature after surgery.

Breast mucoepidermoid carcinoma: a case report and review of literature.

Breast mucoepidermoid carcinoma (MEC) is clinically rare, with an estimated incidence of 0.2-0.3% of all primary breast tumors. To date, only 41 cases have been reported in the literature. Herein, we present a case of breast MEC diagnosed at our hospital. The clinicopathologic features were preliminarily discussed by reviewing the literature. A 42-year-old Chinese woman presented with a lump in her right breast that was detected approximately three months prior. A microscopic examination showed that the breast MEC was composed of different proportions of mucinous cells, intermediate cells, and epidermoid cells. Most mucinous cells were positive for cytokeratin 7, while the epidermoid and intermediate cells were positive for p63 and cytokeratin 5/6. All tumor cells were negative for other myoepithelial markers, such as calponin. Tumor cells did not express estrogen, progesterone, or the HER-2/neu protein. After the patient underwent mastectomy, she was diagnosed with a low-grade mucoepidermoid carcinoma based on the clinical, histologic, and immuno-phenotypic characteristics. Our findings provide further insight into the pathologic mechanism of MEC, as correct diagnosis is essential for patient management.

Importance of the Occipitoaxial Angle and Posterior Occipitocervical Angle in Occipitocervical Fusion.

OBJECTIVE: To observe the effects of occipitoaxial angle (O-C2 angle, OC2A) and posterior occipitocervical angle (POCA) selection on postoperative clinical efficacy and lower cervical curvature in patients with acute acquired atlantoaxial dislocation after occipitocervical fusion (OCF). METHODS: A total of 150 healthy subjects without cervical disease (healthy group) were randomly selected based on gender and age. Three spine surgeons measured the OC2A and POCA of the healthy group and averaged the values. A total of 30 patients with an average age of 51.0 years (range, 18-70 years; 16 male and 14 female) with trauma or rheumatoid arthritis (disease group) who underwent occipitocervical fusion (OCF) for atlantoaxial dislocation between January 2012 and June 2016 were reviewed. OC2A, POCA, and cervical spinal angle (CSA) were measured postoperative/soon after surgery and ambulation, and at the final follow-up visit. The preoperative and final follow-up visual analog scale (VAS), Japanese orthopedics association score (JOA), neck disability index (NDI), and dCSA (change of CSA from postoperative/soon after surgery and ambulation to final follow-up) were recorded. RESULTS: The values of OC2A and POCA in 150 healthy subjects were 14.5° ± 3.7° and 108.2° ± 8.1°, respectively, and the 95% confidence interval (CI) were 7.2°-21.8° and 92.3°-124.0°, respectively. There was a negative correlation between OC2A and POCA (r = -0.386, P < 0.001). There were 18 patients (group one) of ideal OC2A and POCA (both within 95% CI of the healthy group) postoperative/soon after surgery and ambulation with a mean follow-up time of 26.3 ± 20.9 months in disease group. The remaining patients (group two) with a mean follow-up time of 31.3 ± 21.3 months. There was no statistically significant difference in the baseline data as well as pre-operative outcomes, including VAS score, JOA score, and NDI between the two groups. Likewise, the post-operative outcomes in final follow-up, including VAS and JOA score, had no distinct difference in the two groups. However, NDI (11.0 ± 2.9) in group two at the final follow-up was significantly higher than that in group one (7.0 ± 2.3) (P < 0.001). And group two showed statistically greater dCSA (5.9 ± 7.5°) than group one (-2.3° ± 6.2°) (P = 0.003). CONCLUSIONS: The negative correlation between OC2A and POCA plays an important role in maintaining the biodynamic balance of the occipital-cervical region. OC2A and POCA should be controlled of a normal population in patients with acute acquired atlantoaxial dislocation during OCF, which can further improve the clinical efficacy and prevent loss of lower cervical curvature after surgery.

The Antineuroinflammatory Effect of Simvastatin on Lipopolysaccharide Activated Microglial Cells.

Microglial cells, upon hyperactivation, produce proinflammatory cytokines and other oxidative stress mediators causing neuroinflammation, which is associated with the progress of many neurodegenerative diseases. Suppressing the microglial activation has hence been used as an approach for treating such diseases. In this study, the antineuroinflammatory effect of simvastatin was examined in lipopolysaccharide (LPS)-activated rat C6 glioma cells. The cell proliferation and cytotoxic effect of LPS and simvastatin on C6 glioma cells was evaluated by (MTT) assay. Neuroinflammation was induced in differentiated cell lines by treatment with 3.125 µg/mL of LPS for 12 h. Upon induction, the cell lines were treated with different concentrations (3.125, 6.25, 12.5, 25, 50, 100 µM) of simvastatin and incubated in a humidified CO2 incubator for 24 to 48 h. The optimum concentrations of LPS and simvastatin were found to be 3.125 µg/mL and 25 µM, respectively, with a cell viability of more than 90% at 24 h postincubation. Furthermore, proinflammatory marker expression was analyzed by flow cytometry and showed a decrease in interferon-γ, interleukin 6, nuclear factor-κB p65, and tumor necrosis factor-α in simvastatin-treated and LPS-induced neuroinflammatory cells, and the mean fluorescent values were found to be 21.75 ± 0.76, 20.9 ± 1.90, 19.72 ± 1.29, and 16.82 ± 0.97, respectively, as compared to the untreated cells. Thus, we show that simvastatin has the potential to regulate the anti-inflammatory response in microglial cells upon LPS challenge. Hence, simvastatin can be employed as a potent anti-inflammatory drug against neuroinflammatory diseases and neurodegenerative disorders.