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Introduction Elimination or blocking of astrocytes could ameliorate neuropathic pain in animal models. MiR-125a-5p, expressed in astrocyte derived extracellular vesicles, could mediate astrocyte function to regulate neuron communication. However, the role of miR-125a-5p in DPN (diabetic peripheral neuropathy) remains elusive. Materials and methods Type 2 diabetic mouse (db/db) was used as DPN model, which was confirmed by detection of body weight, blood glucose, mechanical allodynia, thermal hyperalgesia, glial fibrillary acidic protein (GFAP) and monocyte chemoattractant protein-1 (MCP-1). Astrocyte was isolated from db/db mouse and then subjected to high glucose treatment. The expression of miR-125a-5p in db/db mice and high glucose-induced astrocytes was examined by qRT-PCR analysis. Downstream target of miR-125a-5p was clarified by luciferase reporter assay. Tail vein injection of miR-125a-5p mimic into db/db mice was then performed to investigate role of miR-125a-5p on DPN. Results Type 2 diabetic mice showed higher body weight and blood glucose than normal db/m mice. Thermal hyperalgesia and mechanical allodynia were decreased in db/db mouse compared with db/m mouse, while GFAP and MCP-1 were increased in db/db mouse. High glucose treatment enhanced the protein expression of GFAP and MCP-1 in astrocytes. Sciatic nerve tissues in db/db mice and high glucose-induced astrocytes exhibited a decrease in miR-125a-5p. Systemic administration of miR-125a-5p mimic increased mechanical allodynia and thermal hyperalgesia, whereas it decreased GFAP and MCP-1. TRAF6 (tumor necrosis factor receptor associated factor 6) was validated as target of miR-125a-5p. Conclusion MiR-125a-5p in astrocytes attenuated DPN in db/db mice by up-regulation of TRAF6, which indicated the potential therapeutic effect.

Elevated blood pressure caused by excessive salt intake is common and associated with cardiovascular diseases in most countries. However, the composition and responses of vascular cells in the progression of hypertension have not been systematically described. We performed single-cell RNA sequencing on the aortic arch from C57BL/6J mice fed a chow/high-salt diet. We identified 19 distinct cell populations representing 12 lineages, including smooth muscle cells (SMCs), fibroblasts, endothelial cells (ECs), B cells, and T cells. During the progression of hypertension, the proportion of three SMC subpopulations, two EC subpopulations, and T cells increased. In two EC clusters, the expression of reactive oxygen species-related enzymes, collagen and contractility genes was upregulated. Gene set enrichment analysis showed that three SMC subsets underwent endothelial-to-mesenchymal transition. We also constructed intercellular networks and found more frequent cell communication among aortic cells in hypertension and that some signaling pathways were activated during hypertension. Finally, joint public genome-wide association study data and our single-cell RNA-sequencing data showed the expression of hypertension susceptibility genes in ECs, SMCs, and fibroblasts and revealed 21 genes involved in the initiation and development of high-salt-induced hypertension. In conclusion, our data illustrate the transcriptional landscape of vascular cells in the aorta associated with hypertension and reveal dramatic changes in cell composition and intercellular communication during the progression of hypertension., High blood pressure: how salt affects cells in the aorta Salt-induced high blood pressure involves dramatic changes in cell composition and communication in blood vessels, a genetic analysis reveals. Over 99% of the world’s adult population has an excessive salt intake, which is associated with hypertension and numerous cardiovascular diseases. Xin Ma and co-workers at Jiangnan University in Wuxi, China, performed single-cell RNA sequencing on aortas from mice that were fed a high-salt diet, and combined their results with genome-wide association studies. They revealed that as hypertension progresses the proportion of smooth muscle cells, cells lining blood vessels, and T cells increases, while several signaling pathways are enriched and new pathways become activated. They also identified 21 associated genes, including Nox4, which promotes collagen synthesis and leads to arterial stiffness. This new understanding provides potential targets for prevention and treatment of hypertension.

Crizotinib is highly efficacious and more tolerable than chemotherapy for ALK+ non-small-cell lung cancer (NSCLC), but its progression-free survival benefit and intracranial efficacy have limitations. Head-to-head comparisons of next-generation ALK inhibitors in patients with ALK+ NSCLC progressing on crizotinib will contribute toward optimizing survival. This international, Phase III, randomized, open-label study (ALTA-3) will therefore assign patients with locally advanced or metastatic ALK+ NSCLC progressing on crizotinib to receive either brigatinib 180 mg qd (7-day lead-in at 90 mg qd) or alectinib 600 mg twice daily. The primary end point is progression-free survival as assessed by a blinded Independent Review Committee; the key secondary end point is overall survival. Clinical trial registration number: NCT03596866 (ClinicalTrials.gov)

Objectives: To compare the perioperative hemodynamic consequences and oncology outcomes of robotic retroperitoneal vs transperitoneal inferior vena cava (IVC) thrombectomy (IVCT) for right...

Migraine is one of the most common and highest burdens of disease. As a primary cerebral dysfunction illness, migraine might exhibit other system-related symptoms, including vestibular and cochlear symptoms. With the publication of the diagnostic criteria of vestibular migraine, the link between migraine and vestibular symptoms became clear. However, the relationship between migraine and cochlear symptoms is far from straightforward. Therefore, we focus on the correlation between migraine and deafness, sudden sensorineural hearing loss, acute tinnitus, and chronic tinnitus to better understand the relationship between migraine and cochlear symptoms.

Objective: The easy liver fibrosis test (eLIFT) is a novel predictor of liver fibrosis in chronic liver disease (CLD). This study aimed to evaluate the predictive value of the eLIFT for liver inflammation and fibrosis in CLD patients. Methods: We enrolled 1125 patients with CLD who underwent liver biopsy. The predictive accuracy for liver inflammation and fibrosis of the eLIFT was assessed and compared to that of the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 score (FIB-4), and gamma-glutamyl transpeptidase-to-platelet ratio (GPR) by ROC (Receiver Operating Characteristic) analysis and decision curve analysis (DCA). Results: The areas under the ROC curves (AUROCs) of the eLIFT for assessing liver inflammation G ≥ 2 and G ≥ 3 were 0.77 (0.75-0.80) and 0.81 (0.79-0.84), with cut-offs of 8.0 and 11.0, respectively. The AUROCs of the eLIFT for predicting fibrosis stages S ≥ 2 and S4 were 0.72 (0.70-0.76) and 0.76 (0.72-0.80), with cut-offs of 9.0 and 10.0, respectively. In discriminating G≥2 inflammation, the AUROC of the eLIFT was better than that of the FIB-4, with no difference compared with the GPR, but lower than that of the APRI. When discriminating G≥3 inflammation, the AUROC of the eLIFT was comparable to that of the APRI and GPR but superior to that of the FIB-4. There were no significant differences between the four indexes for predicting S≥2 and S4. Conclusion: The eLIFT is a potentially useful noninvasive predictor of liver inflammation and fibrosis in patients with CLD.

Background Core needle biopsy (CNB) has become the most common tissue sampling modality for pathological diagnosis of peripheral lung nodules. However, approximately 10% of pulmonary CNB specimens cannot be unambiguously diagnosed, even with auxiliary techniques. This retrospective study investigated the diagnostic value of liquid‐based cytology on residual pulmonary CNB material collected from needle rinses. Methods Computed tomography‐guided pulmonary CNB specimens and relevant cytology of CNB needle rinses (CNR) from July 2017 to June 2020 were reviewed. A total of 406 patients, each of whom underwent a CNB procedure, were included in the study. Results Of the 406 cases, a more serious diagnosis was rendered by CNR in 6.4% (n = 26) of cases. Furthermore, among these 26 cases, 13 malignancies were confirmed only from CNR. Of the remaining 13 patients with uncertain lesions identified from CNR, six were diagnosed with definite benign lesions from tissue samples, five were found to harbor malignant neoplasms through repeated CNB or follow‐up examination, and two had tuberculosis. The sensitivity (320/332, 96.4%) of combined CNR/CNB (both CNR and CNB) in distinguishing malignancies from benign lesions was higher than that of CNB alone (307/332, 92.5%). A total of 320 malignant neoplasms included 198 cases of primary lung adenocarcinoma and 71 cases of primary lung squamous cell carcinoma. Conclusions CNR with higher nuclear and cytoplasmic resolution than CNB exhibited a high diagnostic efficacy for differentiating malignant from benign lesions in the lung. Moreover, combined CNR/CNB achieved optimal results in reducing the false‐negative rate and the subtyping of non‐small cell lung cancer., This retrospective study provides novel insights into a method for evaluating lung nodules in low‐to‐moderate income countries. It elucidates how a combined approach, which utilizes the core needle biopsy (CNB) technique as well as cytology of CNB needle rinses (CNR) containing residual pulmonary CNB material, helps to improve the accuracy and efficacy of diagnosing lung nodules.

Tinnitus is deemed as the result of abnormal neural activities in the brain, and Homer proteins are expressed in the brain that convey nociception. The expression of Homer in tinnitus has not been studied. We hypothesized that expression of Homer in the auditory cortex was altered after tinnitus treatment. Mice were injected with sodium salicylate to induce tinnitus. Expression of Homer was detected by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry assays. We found that Homer1 expression was upregulated in the auditory cortex of mice with tinnitus, while expression of Homer2 or Homer3 exhibited no significant alteration. Effects of two inhibitors of metabolic glutamate receptor 5 (mGluR5), noncompetitive 2-Methyl-6-(phenylethynyl)-pyridine (MPEP) and competitive α-methyl-4-carboxyphenylglycine (MCPG), on the tinnitus scores of the mice and on Homer1 expression were detected. MPEP significantly reduced tinnitus scores and suppressed Homer1 expression in a concentration dependent manner. MCPG had no significant effects on tinnitus scores or Homer1 expression. In conclusion, Homer1 expression was upregulated in the auditory cortex of mice after tinnitus, and was suppressed by noncompetitive mGluR5 inhibitor MPEP, but not competitive mGluR5 inhibitor MCPG.

Objective: To analyze the factors affecting the long-term prognosis of tinnitus accompanied by unilateral idiopathic sudden sensorineural hearing loss (SSNHL). Methods: A total of 161 patients with sudden hearing loss (HL) accompanied by tinnitus were enrolled. All patients had two separate telephone follow-ups and were asked about changes in tinnitus. The severity of tinnitus at admission and the outcome at discharge were assessed in terms of the patients’ sex, age, level of HL, type of audiogram, etc. Results: The prognosis of tinnitus after SSNHL had no relationship with grades of HL or hearing recovery. Initial tinnitus level was remarkably associated with tinnitus improvement at discharge and was an independent risk factor for the long-term prognosis of residual tinnitus after SSNHL (odds ratio 0.722, 95% confidence interval 0.550–0.949, p = 0.019), and the median recovery time was 23.00 ± 3.80 months. Conclusions: Residual tinnitus after SSNHL has a tendency of self-recovery. The short-term prognosis of tinnitus may be related to psychological changes caused by hearing recovery, while the long-term prognosis of residual tinnitus after SSNHL is related only to the initial tinnitus level, with a median recovery time of approximately 2 years.

BackgroundHuman papillomavirus (HPV) infection is associated with multiple types of cancer, but the evidence has not yet been fully elucidated in bladder cancer.MethodsFrozen tissue samples collected from 146 patients aged 32 to 89 years with bladder cancer pathological diagnosis between 2015 and 2019 were analyzed. HPV genotyping and integration status determination were performed by capture-based next generation sequencing. Statistical analysis of HPV type distributions was performed according to stage, grade, sex, and age group of patients.ResultsMean (SD) age of the 146 patients was 66.64 ± 10.06 years and 83.56% were men. Overall HPV infection rate was 28.77% (37.50% in women and 27.05% in men), with 11.90% HPV integration events. Among them, 17.12% single and 11.65% coinfections were observed. HPV18 (24.66%) was the most prevalent genotype, followed by HPV33, 16, and 39. All HPV were European lineage (A). HPV16 was more prevalent in women (P = .04).ConclusionsHPV infection may contribute to the etiology both in men and women with bladder cancer. HPV18, followed by HPV33, 16, and 39 genotypes, potentially represent the predominant oncogenic risk types for bladder carcinogenesis.

The elderly are not only threatened by bad medicines (overtreatment) but also by undertreatment with “good” medicines. Symmetry is required in any patient-centred approach to properly treat older people. The purpose of this study was to perfect the development of an EML and criteria according to the advantages of each and promote the appropriate use of essential medicines in the elderly. We compared the EML with four PIM criteria and calculated the proportion of essential medicines included in the criteria. We also summarized the rationale for including medicines in each criterion and analysed higher risk drugs and drug risks. Of essential medicines, 26% are included in at least one criterion as PIM. In 11 drug categories of the EML, more than 50% of drugs of each category are included in at least one criterion, and in four categories, all drugs are included. The potentially inappropriate essential medicines (PIEMs) for the elderly focus on cardiovascular drugs and central nervous system drugs. Fifty-nine drugs have been explicitly identified as increasing the risk of falls, increasing mortality and/or having inappropriate long-term use, and the main risk of PIEMs is falls (30.3% of PIEMs). Additionally, 17.9% of essential medicines are labelled as positive drugs in START and/or FORTA (A/B). Improving medication information for the elderly in the EML and establishing an essential medicines list for the elderly will promote appropriate drug use in older people worldwide.

Aims Previous studies have shown the intake of omega-3 polyunsaturated fatty acids is associated with low rates of obesity and ischaemic pathologies. Omega-3 also have anti-inflammatory and plaque-stabilization effects and regulate vasodilation and constriction. However, there are few studies of the role of omega-3 in flow-induced vasodilation involving Ca2+-permeable ion channel TRPV4 in high-fat diet-induced obese (DIO) mouse. Here, we determined whether omega-3 protect against vascular dysfunction induced by a high-fat diet by enhancing TRPV4 activity and subsequently improving flow-mediated vasodilation. Methods and results Flow-mediated vasodilation in second-order mesenteric arteries from mice was measured using a pressure myograph. The intracellular Ca2+ concentration in response to flow and GSK1016790A (a TRPV4 agonist) was measured by Fluo-4 fluorescence. Whole-cell current was measured by patch clamp. Cell membrane tether force was measured by atomic force microscopy. Impairment of flow-mediated vasodilation in arteries and Ca2+ influx in endothelial cells from DIO mice was restored by omega-3 treatment. The improved flow-induced vasodilation was inhibited by the TRPV4 antagonist HC067047 and in TRPV4−/− mice. Omega-3 treatment enhanced endothelial TRPV4 activity and altered cell membrane mechanic property, as indicated by enhanced GSK1016790A-induced Ca2+ influx and whole-cell current and altered membrane mean tether force in endothelial cells from DIO mice. Conclusion Omega-3 improve vascular function by improving flow-induced vasodilation via enhancing TRPV4 activity in the endothelium of obese mice which may be related to improved cell membrane physical property. Activation of TRPV4 in endothelium plays an important role in the protective mechanisms of omega-3 against vascular dysfunction in obesity by improving flow-mediated vasodilation.

Background Robot-assisted thrombectomy (RAT) for inferior vena cava (IVC) thrombus (RAT-IVCT) is being increasingly reported. However, the techniques and indications for robot-assisted cavectomy (RAC) for IVC thrombus are not well described. Objective To develop a decision-making program and analyze multi-institutional outcomes of RAC-IVCT versus RAT-IVCT. Design, setting, and participants Ninety patients with renal cell carcinoma (RCC) with level II IVCT were included from eight Chinese urological centers, and underwent RAC-IVCT (30 patients) or RAT-IVCT (60 patients) from June 2013 to January 2019. Surgical procedure The surgical strategy was based on IVCT imaging characteristics. RAT-IVCT was performed with standardized cavotomy, thrombectomy, and IVC reconstruction. RAC-IVCT was mainly performed in patients with extensive IVC wall invasion when the collateral blood vessels were well-established. For right-sided RCC, the IVC from the infrarenal vein to the infrahepatic veins was stapled. For left-sided RCC, the IVC from the suprarenal vein to the infrahepatic veins was removed and caudal IVC reconstruction was performed to ensure the right renal vein returned through the IVC collaterals. Measurements Clinicopathological, operative, and survival outcomes were collected and analyzed. Results and limitations All procedures were successfully performed without open conversion. The median operation time (268 vs 190 min) and estimated blood loss (1500 vs 400 ml) were significantly greater for RAC-IVCT versus RAT-IVCT (both p Conclusions RAC-IVCT or RAT-IVCT represents an alternative minimally invasive approach for selected RCC patients with level II IVCT. Selection of RAC-IVCT or RAT-IVCT is mainly based on preoperative IVCT imaging characteristics, including the presence of IVC wall invasion, the affected kidney, and establishment of the collateral circulation. Patient summary In this study we found that robotic surgeries for level II inferior vena cava thrombus were feasible and safe. Preoperative imaging played an important role in establishing an appropriate surgical plan.

Background Choriocarcinoma is a highly malignant trophoblastic tumor that presents with early symptoms similar to those of an ectopic pregnancy. Here we present a patient with suspected ectopic pregnancy diagnosed by laparoscopic surgery in our hospital. The patient was found to have choriocarcinoma that had metastasized to the lumbar muscle and presented with symptoms similar to those of an ectopic pregnancy. Case summary The patient was a 34-year-old female who complained of amenorrhea lasting 53 d, 7 d of right lower back pain, and 3 d of right lower abdominal pain. Transvaginal ultrasonography revealed the absence of a gestational sac in the uterus and a mass in the left adnexa. After 6 d of re-examination, ultrasound and computed tomography (CT) examination were performed on the mass located in the left adnexa area. We also noted that the patient's serum β-human chorionic gonadotropin (hCG) level was increased. Considering an ectopic pregnancy, we performed a laparoscopy and hysteroscopy. During the operation, a left ovarian mixed echogenic mass approximately 2.5 cm × 2.0 cm with no villous tissue was found. Postoperative levels of serum hCG continued to increase. Lung CT examination showed lung nodules. Both CT and magnetic resonance imaging showed a mixed echogenic mass in the lumbar muscle. Considering lumbar metastasis of choriocarcinoma, six courses of cisplatin, dactinomycin, and etoposide chemotherapy were given after surgery. The patient's serum β-hCG level decreased to normal and the mixed echogenic mass in the lumbar muscle decreased in size after the fifth course of chemotherapy. All symptoms subsequently disappeared after treatment. Conclusion In summary, lumbar metastasis from choriocarcinoma is extremely rare. Appropriate chemotherapy can successfully treat these metastasized tumors.

Objective: Benign paroxysmal positional vertigo (BPPV) has a high recurrence rate, but the risk factor–associated recurrence are elusive. Methods: Searches were performed in PubMed, Embase, Cochrane library, Web of science, Chinese National Knowledge Infrastructure, and Sino Med up to November 3, 2019. The effect size was analyzed by odds ratio and 95% CI. Data from eligible studies were meta-analyzed using Stata version 15.0. Results: Our search resulted in a total of 4076 hits. Twenty-four outcomes of sixty articles were included in the meta-analysis. Risk factors for the recurrence of BPPV included female gender, age (≥65years), hyperlipidemia, diabetes, hypertension, migraine, cervical spondylosis, osteopenia/osteoporosis, head trauma, otitis media, abnormal vestibular evoked myogenic potential, and long use of computers. No significant differences were found in side, type of the involved semicircular canals, smoking, alcohol consumption, stroke, ear surgery, duration of vertigo before treatment, the times of repositioning, Meniere disease, sleep disorders, hypercholesterolemia, and 25-hydroxy vitamin D. Conclusion: These findings strengthen clinical awareness of early warning to identify patients with potential relapse risk of BPPV and clinicians should counsel patients regarding the importance of follow-up after diagnosis of BPPV.

Glucose fluctuations may contribute to large conductance calcium activated potassium (BK) channel dysfunction. However, the underlying mechanisms remain elusive. The aim of this study was to investigate the molecular mechanisms involved in BK channel dysfunction as a result of glucose fluctuations. A rat diabetic model was established through the injection of streptozotocin. Glucose fluctuations in diabetic rats were induced via consumption and starvation. Rat coronary arteries were isolated and coronary vascular tensions were measured after three weeks. Rat coronary artery smooth muscle cells were isolated and whole-cell BK channel currents were recorded using a patch clamp technique. Human coronary artery smooth muscle cells in vitro were used to explore the underlying mechanisms. After incubation with iberiotoxin (IBTX), the Δ tensions (% Max) of rat coronary arteries in the controlled diabetes mellitus (C-DM), the uncontrolled DM (U-DM) and the DM with glucose fluctuation (GF-DM) groups were found to be 84.46 ± 5.75, 61.89 ± 10.20 and 14.77 ± 5.90, respectively (P .05), while the current densities of the BK channels in the three groups were 43.09 ± 4.35 pA/pF, 34.23 ± 6.07 pA/pF and 17.87 ± 4.33 pA/pF, respectively (P .05). The Δ tensions (% Max) of rat coronary arteries after applying IBTX in the GF-DM rats injected with 0.9% sodium chloride (NaCl) (GF-DM + NaCl) and the GF-DM rats injected with N-acetyl-L-cysteine (NAC) (GF-DM + NAC) groups were found to be 8.86 ± 1.09 and 48.90 ± 10.85, respectively (P .05). Excessive oxidative stress and the activation of protein kinase C (PKC) α and nuclear factor (NF)-κB induced by glucose fluctuations promoted the decrease of BK-β1 expression, while the inhibition of reactive oxygen species (ROS), PKCα, NF-κB and muscle ring finger protein 1 (MuRF1) reversed this effect. Glucose fluctuations aggravate BK channel dysfunction via the ROS overproduction and the PKCα/NF-κB/MuRF1 signaling pathway.

OBJECTIVE To present our preliminary experience of robotic left radical nephrectomy (LRN) and segmental inferior vena cava (IVC) resection without caval replacement for left renal cell carcinoma (RCC) with inferior vena cava tumor thrombus. MATERIALS AND METHODS Between 2017 and 2018, 7 patients underwent segmental IVC resection and LRN robotically. All patients underwent preoperative cavography, demonstrating complete IVC occlusion. Computed tomography-based 3-dimensional reconstruction revealed sufficient collateralization of the IVC and right renal vein (RRV). The cephalic IVC was circumferentially resected and ligated just below the second porta hepatis. The caudal IVC was circumferentially resected above the RRV with preservation of the major collaterals. The RRV was not dissected during the procedure to avoid compromising its neocollaterals. The IVC portion between the RRV and the second porta hepatis was removed en bloc with the tumor thrombus, and the LRN was performed. RESULTS All cases were successfully performed by robotic surgery without conversion. Median operative time was 420 minutes. Median intensive care unit stay was 3 days. Four grade Ⅱ complications occurred in 2 patients. One patient had mild LEE postoperatively and recovered without special medication. Median preoperative and 3-6 months follow-up serum creatinine was 118.7 μmol/L and 135.2 μmol/L, respectively. No patient needed dialysis postoperatively. One case occurred disease progression. No patient died during the follow-up period. CONCLUSION Robotic segmental IVC resection for left RCC with inferior vena cava tumor thrombus is feasible in well-selected cases. Three-dimensional reconstruction and cavography are helpful in the preoperative evaluation of neocollaterals in patients with suprarenal IVC occlusion.

Background Recurrent cystic echinococcosis (CE) with vital organ involvement is a challenge for clinicians. Herein, we report a case of aortic involvement in recurrent retroperitoneal CE lesions following primary splenic CE resection. Case summary A 60-year-old male was admitted due to progressive abdominal pain and poor appetite. He was diagnosed with multiple recurrent CE with abdominal aortic involvement according to preoperative evaluation. During surgical resection, major aortic bleeding accidentally occurred while dissecting the cyst, which was firmly attached to the abdominal aortic wall. Hemostasis attempts were conducted to deal with this emergency situation and maintain circulation. Post-interventional recovery was uneventful, and 2-year follow-up showed no sign of recurrence or any other complications. Conclusion Radical resection of recurrent complicated CE with aortic involvement should be carefully planned and performed to prevent possible severe adverse complications, thereby improving the postoperative outcome.

Objective Arthroscopic ankle arthrodesis (AAA) is a standard surgical method for the treatment of advanced traumatic ankle arthritis and has become more popular due to its advantages. To fix the tibiotalar joint, the use of three percutaneous screws is considered to have better mechanical stability than the use of two screws. However, it is sometimes difficult to insert three screws because they might block each other due to the small area of the tibiotalar joint surface and the large diameter of the screws; few articles illustrate how to insert three screws without the screws disturbing each other. The purpose of this study is to explore possible screw configurations of tripod fixation in arthroscopic ankle arthrodesis that avoid the collision of screws and yield better biomechanical performance. Methods We used the finite element method to examine the impact of different screw positions and orientations on the biomechanical characteristics of a three-dimensional (3D) ankle model. Maximum and average micromotion, pressure on the articular surface, and von Mises stress values of the tibia and the talus were used to evaluate the initial stability of the ankle. Results Five kinds of three-screw configurations were identified, and finite element analysis results suggested that configurations with the posteromedial home-run screw presented lower micromotion (maximum, 17.96 ± 7.49 μm versus 22.52 ± 12.8 μm; mean, 4.88 ± 1.89 μm versus 5.19 ± 1.92 μm) (especially configuration 3) and better screw distributions on the articular surface than those with the posterolateral home-run screw. Conclusion Screw configurations with the posteromedial home-run screw avoid collision and are more biomechanically stable than those with the posterolateral home-run screw. Thus, inserting the home-run screw through the posteromedial approach is recommended for clinical practice.

Objective: To explore the diagnostic value of pulmonary ultrasound in patients with coronavirus disease 2019 (COVID-19).Methods: A total of 27 COVID-19 patients (mean age ± standard deviation, 62.6 ± 12.4 years) were enrolled in this study, including 14 males (51.9%) and 13 females (48.1%). Clinical information of these patients was collected, including age, gender, clinical manifestations, medical history, and laboratory indicators. All patients underwent ultrasound examination of their lungs and the results were analyzed.Results: Ultrasound examination of the lungs showed that the lesions in 24 patients were located in both lungs (88.9%), 1 patient's lesions were located in the left lung (3.7%), and 2 patients' lesions were located in the right lung (7.4%). Patients with abnormal lung changes mainly had consolidation, air bronchogram, pisces sign, comet-tail artifact, pleural effusion, fusion B-line, and either multiple or few B-lines.Conclusion: Pulmonary ultrasound examination was a convenient and radiation-free examination method, which could have important clinical value in evaluation of patients with COVID-19.

Supplemental Digital Content is available in the text., Nighttime blood pressure (BP) generally dips by 10% to 20% of the daytime values, and abnormal BP dipping may affect vascular health independently of BP level. The regulation of BP dipping involves arterial baroreflex, whose receptors mainly reside in carotid sinuses and aortic arch. Atherosclerosis in these baroreceptor-resident arteries (BRAs) is frequent among patients with ischemic stroke (IS) and might impair their BP-regulating capacity. We aimed to examine associations between atherosclerosis of BRA and BP dipping in patients with IS. BP dipping ratio was measured by 24-hour ambulatory blood pressure monitoring on the sixth day after IS. With computed tomography angiography, atherosclerosis conditions in 10 segments of carotid sinuses and aortic arch were scored and summed as total atherosclerosis burden of BRA. Among the 245 patients with IS, 78.0% had atherosclerosis in BRA. The total AS burden of BRA was negatively correlated with systolic BP dipping ratio (r=−0.331; P

In clinical practice, objective basis for the choice between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) is scarce. To evaluate surgical outcomes, assess the individual benefit from LPN to RAPN, which can guide clinical decision-making.Patients underwent LPN or RAPN for a localized renal mass in our center between Jan 2013 and Dec 2016 were included. The surgical outcome of LPN and RAPN was the pentafecta achievement. A multivariable model was fitted to predict the probability of pentafecta achievement after LPN. Model-derived coefficients were applied to calculate the probability of pentafecta achievement in case of LPN among patients treated with RAPN. Locally weighted scatterplot smoothing method was applied to plot the observed probability of pentafecta achievement against the predicted pentafecta probability in case of LPN.RAPN group had a significantly higher pentafecta achievement (54.6% vs. 41.1%, P 0.001) than LPN. Multivariable analyses identified that tumor size, distance of the tumor to collecting system or sinus, and preoperative eGFR were independent predictors of pentafecta after LPN. When RAPN was chosen over LPN, the increase in the probability of pentafecta achievement was greatest in intermediate-probability patients. With the increase or decrease of the probability of pentafecta, the benefit of RAPN decreased.When pentafecta achievement are assessed, the benefit of RAPN over LPN varies from patient to patient. Patients at intermediate-probability of pentafecta achievement after LPN benefit the most from robotic surgery, which may be the potential ideal candidates for RAPN.

Diabetes mellitus is a prevalent disease result in several complications, including bone problems. Previous studies have shown that microRNA (miR)-26a regulates glucose metabolism and plays a protective role in diabetes. However, whether miR-26a also affects bone quality in diabetes remains unknown. In the present study, we evaluated the potential effects of miR-26a on bone in diabetic mice. We administrated miR-26a in streptozotocin-induced diabetic mice. The metabolic parameters, bone quality, osteoblast and osteoclast markers, and insulin signaling activation were measured. miR-26a ameliorated insulin resistance and glucose tolerance, improved bone microarchitecture and quality, increased osteoblasts and bone formation, decreased osteoclasts, and promoted the insulin signaling pathway in diabetic mice. These effects were abolished in insulin receptor-compromised Col1a1-Insr+/– mice. In conclusion, miR-26a could ameliorate bone-specific insulin resistance and bone quality in diabetic mice, which depended on the insulin receptors on osteoblasts. Our findings highlight the potential of miR-26a as a therapeutic target for diabetes mellitus-related bone metabolism and diseases., Graphical Abstract, In this study, it is found that miR-26a could ameliorate bone-specific insulin resistance and bone quality in diabetic mice, which depended on the insulin receptors on osteoblasts. The findings highlight the potential of miR-26a as a therapeutic target for diabetes mellitus-related bone metabolism and diseases.

Purpose: Robot-assisted partial nephrectomy (RAPN) is increasingly applied to renal hilar tumors. The present study aims to introduce our vessel and tension-free reconstruction technique and discus...

The aorta, with ascending, arch, thoracic and abdominal segments, responds to the heartbeat, senses metabolites and distributes blood to all parts of the body. However, the heterogeneity across aortic segments and how metabolic pathologies change it are not known. Here, a total of 216 612 individual cells from the ascending aorta, aortic arch, and thoracic and abdominal segments of mouse aortas under normal conditions or with high blood glucose levels, high dietary salt, or high fat intake were profiled using single-cell RNA sequencing. We generated a compendium of 10 distinct cell types, mainly endothelial (EC), smooth muscle (SMC), stromal and immune cells. The distributions of the different cells and their intercommunication were influenced by the hemodynamic microenvironment across anatomical segments, and the spatial heterogeneity of ECs and SMCs may contribute to differential vascular dilation and constriction that were measured by wire myography. Importantly, the composition of aortic cells, their gene expression profiles and their regulatory intercellular networks broadly changed in response to high fat/salt/glucose conditions. Notably, the abdominal aorta showed the most dramatic changes in cellular composition, particularly involving ECs, fibroblasts and myeloid cells with cardiovascular risk factor-related regulons and gene expression networks. Our study elucidates the nature and range of aortic cell diversity, with implications for the treatment of metabolic pathologies.

To determine the impact of intraoperative ultrasound on robotic-assisted radical nephrectomy with inferior vena cava (IVC) tumor thrombectomy in renal cell carcinoma (RCC). We retrospectively analyzed intraoperative records of 27 patients with RCC and invasion of the IVC who underwent robotic-assisted nephrectomy with tumor thrombectomy at our center between December 2017 and July 2018. Diagnostic utility and impact of intraoperative transesophageal echocardiography (TEE), intraoperative robotic-assisted ultrasonography, and intraoperative contrast-enhanced ultrasound (CEUS) on surgical management were extracted from the surgical notes and intraoperative ultrasound reports. Twenty-seven patients with thrombus had intraoperative ultrasound. Complete tumor removal was achieved in 22 patients, IVC transection in 5 patients, and no residual tumor was observed in all patients. Intraoperative TEE changed the robotic surgical strategy in three patients by monitoring thrombus-level regression. Downstaging of the thrombus level occurred in three patients: Levels IV to III in one and Levels III to II in two. Intraoperative robotic-assisted ultrasonography has facilitated safe VC clamp placement and identification and protection of collateral vessels during IVC transection in five patients. Intraoperative CEUS helped to differentiate the boundary between tumor thrombus (enhancement and small vessel pulsation) and bland thrombus (hypoechoic or no enhancement) in eight (29.6%) patients with bland thrombus. Intraoperative ultrasound is a safe, minimally invasive technique that can provide accurate real-time information regarding the presence and extent of IVC involvement and guidance for placement of a vena cava clamp, confirming the character of the thrombus to plan an optimal surgical approach.

Background This study is to determine the risk factors for metastasis of Ewing sarcoma (ES) patients in SEER database. Then explore clinicopathological factors associated with poor prognosis. Furthermore, develop the nomogram to predict the probability of overall survival and cancer-specific survival Methods Thus, we collected clinicopathological data of ES patients in SEER database, and then used chi-square test and logistic regression to determine risk factors associated to metastasis. We also did survival analysis including Kaplan-Meier curve and Cox proportional hazard model to explore the risk factors associated to overall survival and cancer-specific survival, and then developed the nomogram to visualize and quantify the probability of survival. Results After statistics, we find that patients with older ages (11–20 years old: OR = 1.517, 95% confidence interval [CI] 1.033–2.228, p = 0.034; 21–30 years old: OR = 1.659. 95%CI 1.054–2.610, p = 0.029), larger tumor size (> 8 cm: OR = 1.914, 95%CI 1.251–2.928, p = 0.003), and pelvic lesions (OR = 2.492, 95%CI 1.829–3.395, p < 0.001) had a higher risk of metastasis. ROC curves showed higher AUC (0.65) of combined model which incorporate these three factors to predict the presence of metastasis at diagnosis. In survival analysis, patients with older ages (11–20 years: HR = 1.549, 95%CI 1.144–2.099, p = 0.005; 21–30 years: HR = 1.808, 95%CI 1.278–2.556, p = 0.001; 31–49 years: HR = 3.481, 95%CI 2.379–5.094, p < 0.001; ≥ 50 years: HR = 4.307, 95%CI 2.648–7.006, p < 0.001) , larger tumor size (5–8 cm: HR = 1.386, 95%CI 1.005–1.991, p = 0.046; > 8 cm: HR = 1.877, 95%CI 1.376–2.561, p < 0.001), black race (HR = 2.104, 95%CI 1.296–3.416, p = 0.003), and wider extension (regional: HR = 1.373, 95%CI 1.033–1.823, p = 0.029; metastatic: HR = 3.259, 95%CI 2.425–4.379, p < 0.001) were associated with worse prognosis. Chemotherapy was associated with better prognosis (HR = 0.466, 95%CI 0.290–0.685, p < 0.001). The nomogram which developed by training set and aimed to predict OS and CSS showed good consistency with actual observed outcomes internally and externally. Conclusion In conclusion, tumor size and primary site were associated with distant metastasis at diagnosis. Age, tumor size, primary site, tumor extent, and chemotherapy were associated with overall survival and cancer-specific survival. Nomogram could predict the probability of OS and CSS and showed good consistency with actual observed outcomes internally and externally.

Background Efforts have been exerted to establish the correlation between objective variables and subjectively perceived ankle instability. Whether or not biomechanical parameters during stair descent can serve as potential assessment tools for perceived stability in people with unilateral ankle sprain history is unknown. Methods Twenty-four subjects with unilateral ankle sprain history were categorized into four groups according to the severity of perceived stability during stair descent. Kinematic and kinetic parameters during stair descent were obtained with a motion analysis system. Spearman's correlation coefficient (ρ) was utilized to test the correlation between the score of perceived stability during stair descent and biomechanical variables. Findings Subjects with increased perceived instability were likely to show increased ankle inversion (ρ = −0.46, p = .025) and increased ankle plantarflexion (ρ = 0.46, p = .025), with increased hip adduction (ρ = −0.43, p = .036), hip flexion (ρ = −0.56, p = .004), knee adduction (ρ = 0.45, p = .027), and knee flexion (ρ = −0.44, p = .031). No significant correlation was detected between kinetic variables and perceived stability. Interpretation Sagittal and coronal plane motions of the ankle might require rehabilitative intervention to produce improved self-reported outcomes. Kinematic assessment during stair descent can aid in the quantification of subjective ankle instability.

Xuezheng Li,1,2 Yunfeng Deng,2 Junling Wang,2 Hui Jing,2 Wei Shu,3 Jingmin Qin,2 Yu Pang,4 Xin Ma1,2 1School of Public Health, Shandong University, Jinan, People’s Republic of China; 2Katharine Hsu International Research Center of Human Infectious Diseases, Shandong Provincial Chest Hospital, Shandong University, Jinan, People’s Republic of China; 3Clinical Center on TB Control, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 4National Clinical Laboratory on Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of ChinaCorrespondence: Yu PangNational Clinical Laboratory on Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, No 9, Beiguan Street, Tongzhou District, Beijing 101149, People’s Republic of ChinaTel/Fax +86-10-8950 9359Email pangyupound@163.comXin MaSchool of Public Health, Shandong University, No. 44 Wenhuaxi Road, Lixia District, Jinan 250012, People’s Republic of ChinaTel +86-531-6760 7909Fax +86-531-6760 5715Email mx79@hotmail.comBackground: In this study, we aimed to describe the impact of the Genotype® MTBDRplus line probe assay (LPA) for multidrug-resistant tuberculosis (MDR-TB) on total costs in a high-burden setting in China. The second objective was to evaluate the performance of HAIN on smear-positive sputum and clinical isolates.Methods: All definitive TB inpatients at the Shandong Provincial Chest Hospital between May 2012 and May 2017 were included in the study. Two sputum specimens were collected from each patient to conduct smear microscopy, conventional drug susceptibility testing (DST), and the HAIN test. Laboratory and cost data were collected from the electronic medical record system.Results: A total of 1670 definitive TB patients were included in this study. Of these patients, 1307 (78.3%) had smear-positive/culture-positive tuberculosis, and the remaining 363 (21.7%) had smear-negative/culture-positive tuberculosis. The sensitivity and specificity of the HAIN test for RIF resistance was 94.8% (95% confidence interval [CI]: 91.9–97.6%) and 98.8% (95% CI: 98.3–99.4%), respectively. For INH resistance, the sensitivity and specificity was 89.5% (95% CI: 85.7–93.2%) and 95.6% (95% CI: 94.5–96.7%), respectively. The mean time for detection of MDR-TB in smear-negative cases was determined to be 32 days by the HAIN test, which was significantly shorter than that by conventional DST (56 days). Similarly, the mean time for detection of MDR-TB by the HAIN test was significantly shorter than that by conventional DST in smear-positive cases (3 versus 53 days). In addition, by utilizing the HAIN test, the total health care cost decreased by 71.0% for smear-positive cases and 25.9% for smear-negative cases.Conclusion: In conclusion, our data demonstrate that the HAIN test is an accurate rapid test for detecting both RIF and INH resistance in TB patients. The use of the HAIN test can decrease health care costs and reduce the detection time for MDR-TB patients in China, despite the increased costs for laboratory testing.Keywords: tuberculosis, HAIN, multidrug-resistance, performance, cost

Background Endometrial cancer (EC) is one of the three major gynecological malignancies. Numerous biomarkers that may be associated with survival and prognosis have been identified through database mining in previous studies. However, the predictive ability of single-gene biomarkers is not sufficiently specific. Genetic signatures may be an improved option for prediction. This study aimed to explore data from The Cancer Genome Atlas (TCGA) to identify a new genetic signature for predicting the prognosis of EC. Methods mRNA expression profiling was performed in a group of patients with EC (n = 548) from TCGA. Gene set enrichment analysis was performed to identify gene sets that were significantly different between EC tissues and normal tissues. Cox proportional hazards regression models were used to identify genes significantly associated with overall survival. Quantitative real-time-PCR was used to verify the reliability of the expression of selected mRNAs. Subsequent multivariate Cox regression analysis was used to establish a prognostic risk parameter formula. Kaplan–Meier survival estimates and the log‐rank test were used to validate the significance of risk parameters for prognosis prediction. Result Nine genes associated with glycolysis (CLDN9, B4GALT1, GMPPB, B4GALT4, AK4, CHST6, PC, GPC1, and SRD5A3) were found to be significantly related to overall survival. The results of mRNA expression analysis by PCR were consistent with those of bioinformatics analysis. Based on the nine-gene signature, the 548 patients with EC were divided into high/low-risk subgroups. The prognostic ability of the nine-gene signature was not affected by other factors. Conclusion A nine-gene signature associated with cellular glycolysis for predicting the survival of patients with EC was developed. The findings provide insight into the mechanisms of cellular glycolysis and identification of patients with poor prognosis in EC.

The current study aimed to investigate the effects of group reminiscence therapy on cognitive function, depression, neuropsychiatric symptoms, and activities of daily living in patients with mild-to-moderate Alzheimer disease (AD). A single-blind randomized parallel-design controlled trial was conducted between May 1, 2017, and April 30, 2018. Ninety patients with mild-to-moderate AD recruited from Beijing Geriatric Hospital were randomly allocated into intervention (n = 45) and control groups (n = 45). In the intervention group, group-based reminiscence therapy was performed in two 30- to 45-minute sessions weekly for 12 weeks. Control participants received only conventional drug treatments and routine daily care. Alzheimer disease–related symptoms were evaluated using the Alzheimer’s Disease Assessment Scale-Cognitive section, the Cornell Scale for Depression in Dementia (CSDD), the Neuropsychiatric Inventory, and the Barthel Index. Four time points were set for data collection: baseline (before treatment), 4 weeks (during treatment), 12 weeks (end of treatment), and 24 weeks (12 weeks posttreatment). χ2 Tests, independent t tests, repeated-measures analysis of variance, and Bonferroni tests were used for data analysis. Significant improvements in depressive and neuropsychiatric symptoms were found in the intervention group compared to the control group ( P < .05). Mean CSDD scores in the intervention group were improved at all 3 time points compared to baseline and showed the greatest effect at 12 weeks ( t = 2.076, P = .041) and 24 weeks follow-up ( t = 3.834, P = .000) compared to controls. Group reminiscence therapy was effective for improving depressive symptoms and was beneficial for treating neuropsychiatric symptoms in patients with AD.

The purpose of this study was to compare perioperative and oncologic outcomes between laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) for bladder cancer (BCa).Patients who underwent LRC or RARC with curative intent for BCa between January 2011 and December 2016 were included. Perioperative, pathologic oncologic data were extracted from our database. Disease-free survival, overall survival, and cancer-specific survival were analyzed using Kaplan-Meier survival curves with log-rank tests.A total of 126 patients underwent LRC and 189 patients underwent RARC during the study period. All the baseline variables were similar between the two groups. Patients undergoing RARC had a significant higher median estimated blood loss (300 mL vs. 200 mL; P = .005), lower rate of 90-day postoperative complications (36.5% vs. 50.0%; P = .017), and higher median direct cost ($15,306 vs. $11,131; P .001) than LRC. Other perioperative outcomes were similar. No differences were found in pathologic T stage, positive lymph nodes, or positive surgical margin between patients who underwent LRC and RARC. The 5-year disease-free survival, overall survival, and cancer-specific survival rates were 51.9%, 61.0%, and 69.5%, respectively, for all included patients. There were no significant differences in oncologic outcomes between the 2 groups.Patients with BCa can be safely managed with LRC and RARC by experienced surgeons. RARC was associated with a reduced rate of postoperative complication but also with higher median estimated blood loss, and higher median direct cost. These findings could be used to guide patient counseling, and treatment selection.

Aim Cervicocephalic atherosclerosis (AS) of patients with large-artery atherosclerotic (LAA) stroke might be more closely correlated to the functional outcome than patients with stroke of other etiologies. We aimed to investigate whether a whole-scope evaluation of cervicocephalic AS condition was better at predicting the 90-day functional outcome of LAA stroke than evaluation of intracranial or cervical AS condition alone. Methods Patients with LAA stroke were consecutively enrolled in this study. Computed tomography angiography was performed to evaluate AS condition of various cervicocephalic arterial segments. AS conditions ranging from no AS plaque to complete arterial occlusion scored 0-4 points. Intracranial atherosclerotic burden (IAB) and cervical atherosclerotic burden (CAB) were in respective the sums of AS scores of all intracranial arterial segments and all cervical arterial segments. And the sum of them was intracranial and cervical atherosclerotic burden (ICAB). Relationships of these three scores with the 90-day unfavorable functional outcome (modified Rankin Scale[mRS] score ＞2 points) were compared. Results Of 172 patients who finished 90-day follow-up, only ICAB (adjusted odds ratio[OR]=1.10, 95% confidence interval[CI]:1.00-1.21, p=0.044) predicted 90-day unfavorable functional outcome independently of clinical factors, National Institutes of Health Stroke Scale (NIHSS) and mRS scores at admission. ICAB (adjusted hazard ratio[HR]=1.16, 95%CI:1.02-1.32, p=0.029) was related to 90-day recurrent ischemic stroke/death independently of clinical factors and was independently, positively correlated with NIHSS score at admission (r=0.16, p=0.047), whereas IAB and CAB were not. Conclusion A whole-scope evaluation of cervicocephalic AS condition using ICAB outperformed evaluation of intracranial or cervical AS condition alone in predicting 90-day functional outcome of patients with LAA stroke.

Objective: The relation between cognition and hearing loss has been increasingly paid high attention, however, few studies have focused on the role of high-frequency hearing loss in cognitive decline. This study is oriented to role of hearing loss especially high-frequency hearing loss in cognitive impairment among elderly people (age ≥ 60 years).Methods: The Montreal Cognitive Assessment Scale (MoCA) and pure tone audiometry were used to investigate the hearing loss and cognitive function of 201 elderly people older than 60 years. Factors possibly related to cognitive impairment including age, years of education, occupation, living conditions, history of otologic diseases, and high blood pressure were registered. This study consisted of two parts. First, univariate analysis and multiple linear regressions were performed to analyze the possible influencing factors of cognitive function among the 201 elderly people. Second, average hearing thresholds of low frequencies (250, 500 Hz), intermediate frequencies (1 k, 2 kHz), and high frequencies (4 k, 8 kHz) were calculated to screen out 40 cases with high-frequency hearing loss alone and 18 cases with normal hearing. Univariate analysis was used to compare the general condition, cognitive function, and each cognitive domain between the two groups, analyzing the relation between high-frequency hearing loss and cognitive function.Result: We found that age, years of education, pure tone average (PTA), occupation, living condition, history of otologic diseases, years of self-reported hearing loss, and hypertension history were related to cognitive function. Furthermore, age, education experience, duration of self-reported hearing loss, and hypertension were independent factors (p < 0.05). PTA was negatively related with attention, orientation, and general cognition (p < 0.05). There were only 18 cases (9.0%) with normal hearing, and 40 cases (19.9%) with abnormal high-frequency hearing alone. The overall cognitive function showed no significant difference between them (p > 0.05); in contrast, the speech and abstract ability were significantly decreased in cases with high-frequency hearing loss (p < 0.05).Conclusion: The increase of PTA among the elderly may affect the overall cognition by reducing attention and orientation. High-frequency hearing loss alone can affect the language and abstract ability to a certain extent, which is worthy of more attention.

Tinnitus, acute or chronic, is one of the most common and refractory disorders. Acute tinnitus is a symptom that is a warning sign when compared with chronic tinnitus. Although hearing loss initiates acute tinnitus, the relationship between hearing loss and tinnitus is far from straightforward. Other factors beyond the auditory system may play important roles in the occurrence of acute tinnitus. To address this issue, we propose an integrated regulation theory of the possible physical causes of acute tinnitus, and summarize a classification system for acute tinnitus based on this regulation theory to help guide clinical treatment.

Objectives: To evaluate the prognostic value of preoperative lymphocyte to monocyte ratio (LMR) in patients with renal cell carcinoma and venous tumor thrombus (RCC-VTT) after surgery. Methods: We retrospectively reviewed the medical data of 144 consecutive patients with RCC and level I-IV VTT after surgery. Kaplan-Meier method was used to assess and compare survival. Univariable and multivariable Cox proportional hazard models were constructed to identify the independent prognostic factor for survival. The Harrell concordance index was used to assess the predictive accuracy. Results: Decreased preoperative LMR was significantly correlated with clinicopathologic features that are associated with tumor progression. Decreased preoperative LMR was an independently risk factor for decreased OS (P < 0.05) and PFS (P < 0.05). To evaluate PFS, integrating LMR to each model led to an increased predictive accuracy of 6.9% for TNM staging model (P = 0.014), 6.8% for UISS model (P = 0.006), 3.4% for SSIGN model (P = 0.017), respectively. Incorporating LMR into SSIGN model led to an increased predictive accuracy of 6.5% for OS (P < 0.001). Conclusions: Preoperative LMR is an independent prognostic factor for patients with RCC-VTT after surgery. Adding preoperative LMR to the prognostic models enhance their predictive accuracy.

IntroductionPostoperative delirium is one of the most common postoperative complications among elderly patients (65 years old or older). However, there are no effective treatments for this condition. Recent research suggests that continuous theta burst stimulation (cTBS), a non-invasive brain stimulation, can reduce pain level, improve cognitive function and affective symptoms in multiple diseases or dysfunctions, including anxiety disorders, major depressive disorder, sleep disorders and pain. But the potential benefits of cTBS in reducing postoperative delirium have not been investigated. Therefore, we propose determining whether cTBS can prevent and/or treat postoperative delirium in senior patients.Methods and analysisThe study will be a double-blind, randomised controlled trial. Participants (65 years old or older) undergoing scheduled orthopaedic surgery (≥2 hours, general anaesthesia) will be randomised to receive either cTBS or sham stimulation with a focal figure-of-eight coil over the right dorsolateral prefrontal cortex at 80% of the resting motor threshold. Every patient will receive 2–3 sets of stimulations during postoperative days (40 s per session, 3 sessions per set, 1 set per day). Participants will be assessed twice daily by a research assistant blinded to allocation. The primary outcome will be the incidence of postoperative delirium measured by the Confusion Assessment Method on postoperative days 1, 2 and 3. The secondary outcomes will be the severity and duration of postoperative delirium, cognitive function, pain, sleep quality, activities of daily living, length of hospital stay, discharge-to-facility or home, and rate of complication and mortality during the hospital stay.Ethics and disseminationEthical approval has been obtained from the ethics committee of Shanghai 10th People’s Hospital. The principal investigator will submit a research progress report to the ethics committee regularly. All participants will provide written informed consent. Study results will be published in a peer-reviewed journal.Trial registration numberNCT04661904.

BACKGROUND: Migraine is more common in Meniere’s disease patients, who have some certain anatomical variations. But there are limited studies focusing on the anatomical variations in patients with Meniere’s disease and migraine. OBJECTIVE: To explore the clinical and anatomical features in Meniere’s disease patients with and without migraine, determining whether the coexistence of migraine can be used as a basis for clinical subtyping of Meniere’s disease. METHODS: Ninety-five Meniere’s disease patients and ninety-five healthy subjects matched with age, sex were selected. A detailed questionnaire based on the diagnosis criteria of Meniere’s disease and migraine was designed. According to the CT scan, we divided the mastoid cell system of all the subjects into two types: well-pneumatization type and poor-pneumatization type. Meanwhile, the shortest distance between the sigmoid sinus and the posterior wall of the external acoustic canal was measured. RESULTS: Compared with those without migraine, Meniere‘s disease patients with migraine had a higher female comorbidity, poorer mastoid pneumatization, shorter distance between the sigmoid sinus and posterior wall of the external acoustic canal, longer history, higher frequency of vertigo attacks and better average hearing threshold. CONCLUSIONS: In our study, anatomical features as well as several clinical manifestations were proved to differ significantly between Meniere’s disease patients with and without migraine, indicating the coexistence of migraine may be one standard for the clinical subtyping of Meniere’s disease.

The link between posttraumatic stress disorder (PTSD) and ischemic heart disease remains elusive owing to a shortage of longitudinal studies with a clinical diagnosis of PTSD and objective measures of cardiac compromise.We performed positron emission tomography in 275 twins who participated in two examinations approximately 12 years apart. At both visits, we obtained a clinical diagnosis of PTSD, which was classified as long-standing (both visit 1 and visit 2), late onset (only visit 2), and no PTSD (no PTSD at both visits). With positron emission tomography, we assessed myocardial flow reserve (MFR), which, in absence of significant coronary stenoses, indexes coronary microvascular function. We compared positron emission tomography data at visit 2 across the three categories of longitudinally assessed PTSD and examined changes between the two visits.Overall, 80% of the twins had no or minimal obstructive coronary disease. Yet, MFR was depressed in twins with PTSD and was progressively lower across groups with no PTSD (2.13), late-onset PTSD (1.97), and long-standing PTSD (1.93) (p = .01). A low MFR (a ratio2.0) was present in 40% of the twins without PTSD, in 56% of those with late-onset PTSD, and in 72% of those with long-standing PTSD (p.001). Associations persisted in multivariable analysis, when examining changes in MFR between visit 1 and visit 2, and within twin pairs. Results were similar by zygosity.Longitudinally, PTSD is associated with reduced coronary microcirculatory function and greater deterioration over time. The association is especially noted among twins with chronic, long-standing PTSD and is not confounded by shared environmental or genetic factors.

ObjectiveThe purpose of this study was to develop a non-invasive and convenient nomogram based on speckle tracking echocardiography, left atrial appendage function and clinical factors to predict the risk of atrial fibrillation (AF) recurrence after catheter ablation.MethodsA total of 124 prospectively consecutive patients with AF treated with catheter ablation in our hospital was retrospectively analysis. Baseline echocardiographic parameters were measured by using transthoracic and transesophageal echocardiography before ablation. Multivariate analysis was performed for selecting predictors for a nomogram and internal validation and calibration were evaluated by the bootstep method.ResultsDuring the follow-up of 12±3 months, 41 patients (33.1%) occurred AF recurrence after catheter ablation, while 83 patients (66.9%) had maintained sinus rhythm. Four predictors (AF type, left atrial appendage emptying flow velocity, left Atrial maximal volumes index and global longitudinal strain) with the PConclusionsNomogram based on echocardiography and clinical characteristics had good predictive performance for the possibility of AF recurrence, which providing practical guidance for individualised management of patients with AF after catheter ablation.

Background: Electroconvulsive therapy is an important somatic treatment for severe mental disorders with established efficacy and safety. However, data on the relationship between ECT and the readmission rate of patients with schizophrenia are scarce. This study will explore the association between the administration of ECT and readmission rates using a machine learning method. Methods: Inpatient medical records from the year of 2016 in one large psychiatric hospital in Beijing, China, were analyzed using a machine learning algorithm to determine the most important variables affecting readmission of patients with schizophrenia. Results: The medical records of 2131 inpatients with schizophrenia were reviewed. 1099 patients were followed up within 3 months of their index admission (642 ECT cases and 457 non-ECT cases) and 1032 patients were followed up within 6 months (596 ECT cases and 436 non-ECT cases) after discharge. The 3- and 6-month readmission rates in the ECT group (11.37% and 17.94%, respectively) were significantly lower than that of the patients who did not receive ECT (18.79% and 29.36%, respectively, both p

Background The hepatotoxicity and cardiotoxicity caused by neoadjuvant chemotherapy (NAC) are of increasing concern to clinicians in breast cancer (BC) patients. The aim of this study was to investigate the prevalence of chemotherapy-associated steatohepatitis (CASH), quantitate the epicardial adipose tissue (EAT) volume in BC patients, and explore the correlations of these parameters with blood lipid levels in BC patients who received NAC. Methods From October 2018 to April 2020, BC patients were retrospectively reviewed. Clinical and laboratory data were collected. The patients were divided into BC-non-NAC group and BC-NAC group (BC-NAC subgroups 1 ~ 4 according to the number of NAC cycles). The prevalence of CASH was evaluated using quantitative MRI mDIXON-Quant examinations, from which the proton density fat fraction (PDFF) was assessed. The EAT volume was quantified on chest CT by semi-automatic volume analysis software. Pearson correlation coefficients were calculated for the associations among PDFF values, EAT volumes and blood lipid levels. Results A total of 662 women (BC-non-NAC group: 445 patients; BC-NAC group: 217 patients) were included. The prevalence of CASH in BC-NAC group was significantly higher than the prevalence of hepatic steatosis in the BC-non-NAC group (42.8% vs. 33.3%, p p = 0.034). EAT volume was measured in 561 of 662 BC patients, and was significantly higher in the BC-NAC group than in the BC-non-NAC group (137.26 ± 53.48 ml vs. 125.14 ± 58.77 ml, p = 0.020). A moderate positive correlation was observed between the hepatic PDFF value and EAT volume (r = 0.411, p r = 0.386, p = 0.004; r = 0.338, p

Dopamine-β-hydroxylase (DβH) is an enzyme converting dopamine to norepinephrine, a key neurotransmitter in mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD). Due to overlapping symptomology of unipolar and bipolar depression, the present study attempted to explorer if the plasma DβH activity could discriminate the depressive episodes of BD from MDD. The aim of this study was to compare the plasma DβH activity among MDD patients (n = 104), BD patients (n = 101), and healthy controls (n = 160). Clinical characteristics and cognitive function were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Patient Health Questionnaire-9 (PHQ-9), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Our data showed a lower plasma DβH activity in patients with BD, not MDD, than that in controls. For the BD patients, the plasma DβH activities were negatively correlated with HAM-D scores and HAM-A scores. However, there was no significant correlation between plasma DβH activity and severity of depressive symptoms in MDD patients. No significant correlation between DβH activities and cognitive assessments neither in BD nor in MDD patients. The present study provides evidence that BD is associated with decreased circulating DβH activity.

BackgroundPrepulse inhibition (PPI) is a measurement method for the sensory gating process, which helps the brain adapt to complex environments. PPI may be reduced in patients with bipolar disorder (BD). This study investigated PPI deficits in BD and pooled the effect size of PPI in patients with BD.MethodsWe conducted a literature search on PPI in patients with BD from inception to July 27, 2019 in PubMed, Embase, Cochrane Library databases, and Chinese databases. No age, sex, and language restriction were set. The calculation formula was PPI = 100 - [100*((prepulse - pulse amplitude) / pulse amplitude)]. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies.ResultsTen eligible papers were identified, of which five studies including a total of 141 euthymic patients and 132 healthy controls (HC) were included in the meta-analysis. Compared with HC, euthymic patients with BD had significantly lower PPI at the 60 ms interstimulus interval (ISI) between pulse and prepulse (P = 0.476, I2 = 0.0%, SMD = − 0.32, 95% CI = − 0.54 - -0.10). Sensitivity analysis shows no significant change in the combined effect value after removing any single study. There was no publication bias using the Egger’s test at 60 ms (P = 0.606). The meta-analysis of PPI at the 60 ms ISI could have significant clinical heterogeneity in mood episode state, as well as lack of data on BD I or II subtypes.ConclusionsEuthymic patients with BD show PPI deficits at the 60 ms, suggesting a deficit in the early sensory gate underlying PPI. The PPI inhibition rate at a 60 ms interval is a stable index. More research is needed in the future to confirm this outcome, and to delve deeper into the mechanisms behind deficits.

Background Previous studies showed functional ankle instability (FAI) patients have morphological ligamentous abnormality, despite having no apparent joint laxity. Research question Whether tibiotalar and subtalar joints hypermobility exists in FAI patients during stance phase of walking, remains controversial. Methods Ten unilateral FAI patients, ten unilateral lateral ankle sprain (LAS) copers and ten healthy controls were included. A dual fluoroscopy imaging system was utilized to capture the fluoroscopic images of tibiotalar and subtalar joint during the stance phase of walking. Kinematic data from six degrees of freedom were calculated utilizing a solid modeling software. The range of motion and joint excursions about six degrees of freedom were compared among the three groups. The correlations between range of motion and Cumberland Ankle Instability Tool (CAIT) scores were assessed utilizing the Spearman’s correlation coefficient (r). Results During the stance phase, the FAI patients and LAS copers showed larger tibiotalar anterior/posterior translation than the healthy controls (FAI patients, p = .013; LAS copers, p = .002). The FAI patients also showed significantly larger lateral/medial translation (p = .035) and inversion/eversion rotation (p = .003) of subtalar joints than healthy controls. By contrast, the subtalar joints of the LAS copers were not different from those of the healthy controls in the lateral/medial translation (p = .459) and inversion/eversion rotation (p = .091). CAIT scores were negatively correlated with range of motion. Significance During the stance phase of walking, FAI patients showed significantly larger hypermobility of subtalar joints than healthy controls, contrary to the LAS copers. These findings justify the utilization of dual fluoroscopy imaging system to detect joint hypermobility in FAI patients. Treatment for FAI patients may require stabilization of the subtalar joint.

Isoliquiritigenin (ISL) is a flavonoid substance with a chalcone structure, which exerts anti-tumour, anti-oxidation and anti-inflammatory activity. The large-conductance calcium-activated potassium channel (BKC a ) is an important potassium channel with negative feedback regulation on the vascular smooth muscle cells (VSMCs) membrane. The activation of BKC a channel causes the hyperpolarization of VSMCs. It plays an important role in relaxation of blood vessels. Previous studies have shown that ISL causes the relaxation of the aorta and the basilar artery of the rat. However, there have not been studies on regulation of ISL in mesenteric arteries. To examine whether ISL causes the relaxation of the mesenteric artery of mice, we recorded vasodilation of mouse mesenteric arterial rings with a myograph. After contraction of arterial rings with phenylephrine, we added ISL to the arterial rings and measured its relaxation effect. To further examine which channel was involved in this relaxation effect, we tested the effects of ISL on endothelium-dependent and endothelium-independent vasodilation. Then we used BKC a channel blockers tetraethylammonium and iberiotoxin, to detect whether the BKC a channel is involved in ISL-induced vasodilation. Mesenteric arterial smooth muscle cells were isolated by enzyme digestion. Bis-(1, 3-dibutylbarbituric acid) trimethine oxonol staining was used to measure membrane potential of mesenteric arterial smooth muscle cells. We identified a vasodilation effect caused by ISL on mouse mesenteric arterial rings pre-contracted by phenylephrine in a concentration-dependent manner, with an EC50 of 13.71 ± 1.1 μmol/L. The vasodilation effect of ISL is endothelium-independent. K+ channel inhibitors tetraethylammonium and iberiotoxin reduced the vasodilation induced by ISL which suggested the involvement of BKC a channel.

Complex aortic plaque is a potential cause of acute ischemic cerebrovascular disease, which needs timely identification. Also as a marker for systemic atherosclerosis, complex aortic plaque may be indicated by significant (≥50%) cervicocephalic atherosclerotic stenosis. We aimed at examining whether age ranges would influence their association to more accurately estimate the risk of having complex aortic plaque in acute ischemic cerebrovascular disease.Aortic arch and cervicocephalic arteries were simultaneously evaluated using computed tomography angiography. Middle-aged (45-64 years) and old-aged (65-85 years) acute ischemic cerebrovascular disease patients were divided into 2 groups according to whether there was an aortic arch plaque with thickness of greater than or equal to 4 mm or associated ulcerations or mural thrombus.Old-aged patients (n = 107) had a higher prevalence of complex aortic plaque (67.3% versus 30.9%, P.001) than those middle aged (n = 178). Among middle-aged patients, the presence of extracranial significant atherosclerotic stenosis (adjusted odd ratio = 2.89, 95% confidence interval: 1.42-5.86) rather than intracranial ones independently predicted complex aortic plaque. Regarding the extent of significant cervicocephalic atherosclerotic stenosis, the presence of multi-segment, bilateral, simultaneous extracranial and intracranial, and simultaneous anterior and posterior circulation ones were independent indicators for complex aortic plaque in the middle-aged subgroup (adjusted odd ratio = 2.42, 2.05, 2.26, 2.14, respectively). By contrast, no statistical correlation of complex aortic plaque and significant cervicocephalic atherosclerotic stenosis was found among old-aged patients.Considering the ranges of age was important to more precisely predict complex aortic plaque with significant cervicocephalic atherosclerotic stenosis in acute ischemic cerebrovascular disease.

Patients with mechanic ankle instability experience increased tibiotalar and subtalar joint laxity. However, in vivo joint kinematics in functional ankle instability (FAI) patients and lateral ankle sprain (LAS) copers, especially during dynamic activities, are poorly understood. Ten FAI patients, 10 LAS copers, and 10 healthy controls were included in this study. A dual fluoroscopic imaging system was used to analyze the tibiotalar and subtalar joint kinematics during stair descent. Five key poses of stair descent were analyzed. Kinematic data from six degrees of freedom were calculated utilizing a solid modeling software. The range of motion and joint positions in each degree of freedom were compared among the three groups. The tibiotalar joints of FAI patients and LAS copers were significantly more inverted than those of healthy controls during the foot strike (p = 0.016, η p 2 = 0.264). The subtalar joints of FAI patients were significantly more anteriorly translated (pose 2, p = 0.003, η p 2 = 0.352; pose 3, p η p 2 = 0.454; pose 4, p = 0.004, η p 2 = 0.334), inverted (pose 4, p = 0.027, η p 2 = 0.234; pose 5,p = 0.034, η p 2 = 0.221), and externally rotated (pose 4, p = 0.037, η p 2 = 0.217; pose 5; p = 0.004, η p 2 = 0.331) than those of healthy controls during the mid-stance and the heel off. The FAI patients showed excessive tibiotalar inversion and subtalar joint hypermobility during stair descent. Meanwhile, the LAS copers maintained subtalar joint stability, and only showed excessive tibiotalar inversion in foot strike. These data provide insight into the mechanisms behind the development of FAI after initial LAS. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1860-1867, 2019.

Background:. Asymptomatic coronary artery stenosis (ACAS) ≥50% is common in patients with acute ischemic cerebrovascular disease (AICVD), which portends a poor cardiovascular and cerebrovascular prognosis. Identifying ACAS ≥50% early may optimize the clinical management and improve the outcomes of these high-risk AICVD patients. This study aimed to investigate whether aortic arch plaque (AAP), an early atherosclerotic manifestation of brain blood-supplying arteries, could be a predictor for ACAS ≥50% in AICVD. Methods:. In this cross-sectional study, atherosclerosis of the coronary and brain blood-supplying arteries was simultaneously evaluated using one-step computed tomography angiography (CTA) in AICVD patients without coronary artery disease history. The patients were divided into ACAS ≥50% and non-ACAS ≥50% groups according to whether CTA showed stenosis ≥50% in at least one coronary arterial segment. The AAP characteristics of CTA were depicted from aspects of thickness, extent, and complexity. Results:. Among 118 analyzed patients with AICVD, 29/118 (24.6%) patients had ACAS ≥50%, while AAPs were observed in 86/118 (72.9%) patients. Increased AAP thickness per millimeter (adjusted odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.18–2.05), severe-extent AAP (adjusted OR: 13.66, 95% CI: 2.33–80.15), and presence of complex AAP (adjusted OR: 7.27, 95% CI: 2.30–23.03) were associated with ACAS ≥50% among patients with AICVD, independently of clinical demographics and cervicocephalic atherosclerotic stenosis. The combination of AAP thickness, extent, and complexity predicted ACAS ≥50% with an area under the receiver-operating characteristic curve of 0.78 (95% CI: 0.70–0.85, P