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Mode-locked lasers with low noise performance, such as low timing jitter and relative intensity noise are essential for high-precision applications. In this letter, we demonstrated a 122-MHz all-polarization-maintaining mode-locked Er-doped fiber laser based on a nonlinear amplifying loop mirror. A hybrid component integrating a wavelength division multiplexer and a phase shifter is applied to increase the repetition rate. The relative intensity noise is 0.004% and 0.76% rms (integrated from 1 MHz to 100 Hz) from two output ports. The timing jitter characteristic is measured by the delayed optical heterodyne method. The timing jitter is ~1.9 fs rms (integrated from 1 MHz to 10 Hz) of both two output ports. The origin of the timing jitter of this laser is analyzed numerically based on the well-established theoretical model using the laser’s repetition rate, cavity dispersion, etc.

Objective/Background Proliferation is a widely recognized trigger for pulmonary hypertension (PH), a life‐threatening, progressive disorder of pulmonary blood vessels. This study was aimed to identify some proliferation associated genes/targets for better comprehension of PH pathogenesis. Methods Human pulmonary arterial smooth muscle cells (hPASMCs) were cultured in the presence or absence of human recombinant platelet derived growth factor (rhPDGF)‐BB. Cells were collected for metabolomics or transcriptomics study. Gene profiling of lungs of PH rats after hypoxia exposure or of PH patients were retrieved from GEO database. Results 90 metabolites (VIP score >1, fold change >2 or 2 or, Proliferation associated hub genes in pulmonary arterial smooth muscle cells (PASMCs) in response to platelet derived growth factor‐BB (PDGF‐BB) were explored by virtue of transcriptomics and metabolomics. Those hub genes might be responsible for proliferating PASMCs phenotype and associated with immune cell infiltrates into the lung tissues, contributing to the development of pulmonary vascular remodeling (created with BioRender.com).

The purpose was to explore the value of high on-treatment platelet reactivity (HTPR) in predicting long-term clinical outcomes for stroke patients. The platelet reactivity was assayed after being treated with either 75 mg clopidogrel or 100 mg aspirin daily with VerifyNow System in stroke patients. HTPR for clopidogrel was defined as PRU ≥ 208, and that for aspirin was defined as ARU ≥ 550. CYP2C19 genotyping was performed using the Sequenom MassARRAY iPLEX platform. The primary endpoint was a composite of recurrent ischemic stroke, transient ischemic attack, myocardial infarction, or ischemic vascular death. The safety endpoint was bleeding. In the clopidogrel group, among 345 patients recruited, 174 of them were categorized as HTPR. A total of 270 patients were followed up for 54 months. There was a significant association between HTPR and the primary endpoint (HRadj 2.13 [95% CI, 1.43–3.15], p

This paper describes a computer-based finite element (FE) approach for investigating the stiffness and resistance behaviour of beam-column moment joints in the portal frame constructed by cold-formed steel (CFS) back-to-back channel sections. A total of 8 specimens constructed by flat sheets and bolt are tested in the study. The applicability of the numerical simulation approach is validated against the experimental outcomes. Based on the FE simulations, a modified equation is proposed to predict the initial flexibility of four-layer CFS lap joints under tension. Parametric studies consisting of 18 four-layer bolted connections and 27 beam-column bolted models are conducted based on the validated model to investigate the effects of sheet width-to-thickness ratio, bolt-to-bolt hole tolerance and overlap length on the flexibility of the connection and to reveal the influence of bolt spacing, gusset plate thickness and beam profile on the failure behaviours, moment transfer coefficients and ultimate resistance of CFS beam-column moment joints. The FE obtained results indicate that increasing bolt spacing is a better option to improve the joint capacity when compared with increasing gusset plate thickness. The flexural capacity of the CFS bolted built-up joints with varying sectional configurations can meet the criterion of the existing design specifications such as Eurocode and US code.

Gradual distraction with an external fixator is a widely used treatment for severe postburn ankle contracture (SPAC). However, application of external fixators is complex, and conventional two-dimensional (2D) imaging-based surgical planning is not particularly helpful due to a lack of spatial geometry. The purpose of this study was to evaluate the surgical planning process for this procedure with patient-specific three-dimension-printed models (3DPMs). In this study, patients coming from two centers were divided into two cohorts (3DPM group vs. control group) depending on whether a 3DPM was used for preoperative surgical planning. Operation duration, improvement in metatarsal-tibial angle (MTA), range of motion (ROM), the American Orthopedic Foot and Ankle Society (AOFAS) scores, complications, and patient-reported satisfaction were compared between two groups. The 3DPM group had significantly shorter operation duration than the control group ((2.0±0.3) h vs. (3.2± 0.3) h, P

Objective This research was performed to investigate the correlation between acute kidney injury (AKI) and systemic immune-inflammation index (SII) in severe acute pancreatitis (SAP) patients. Methods The study included 218 SAP patients from Chongqing Jiangjin Center Hospital during January 2016 to October 2020. The SII was defined as platelet × neutrophil/lymphocyte ratio. After univariate analysis, logistic regression analysis was used for analyzing independent risk factors of AKI in SAP patients. Receiver operating characteristic (ROC) curve was used for analyzing the prognostic value of the SII. Results AKI occurred in 74 cases and its incidence rate was 33.9%. The median SII value of AKI patients was higher than that of patients without AKI. After multivariate analysis, SII, age, triglyceride (TG), neutrophil ratio (NEU-R), C-reactive protein (CRP), aspartate aminotransferase (AST), and serum albumin (ALB) were independent predictors of AKI. Serum ALB was an independent protective factor. The optimum threshold truncation value of SII was 2880.1*10^9/L. Compared with other inflammatory factors, SII had a better prediction efficiency. Conclusion The SII, TG, NEU-R, CRP, and ALB were significant independent predictors of AKI in SAP patients. Serum TG, NEU-R, CRP, and SII were risk factors. Serum ALB was a protective factor. The SII may be a novel, simple, and strong marker for the accurate early prediction of AKI in SAP patients.

Depression is a serious neuropsychiatric disorder, which is characterized by sustaining mood disorders. Loganin, a major iridoid glycoside from Corni fructus, has a variety of pharmacological activities, including neuroprotective effect and hypnotic effect. However, little is known about the effects of loganin on stress-induced depression. To investigate the effects of loganin on behavioral despair of mice, and whether serotonin (5-HT) and/or noradrenaline (NE) are involved in this process. We tested the effectiveness of loganin using tail suspension test (TST). The possible mechanism was explored using reserpine-induced ptosis and hypothermia, and 5-HTP-induced head-twitch response in mice. The changes of 5-HT and NE in the prefrontal cortex, hippocampus, and striatum were measured through high-performance liquid chromatography (HPLC) analysis. Then, we identified the effects of depleting 5-HT and NE by PCPA (p-chlorophenylalanine) and DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) pretreatment, respectively. Loganin (12.5/50 mg/kg) induced antidepressant-like effects in mice submitted to TST. Loganin (12.5/50 mg/kg) ameliorated the reserpine-induced hypothermia and ptosis, as well as increased 5-HTP-induced head-twitch responses in mice. Loganin (50 mg/kg) significantly increased the levels of 5-HT in the prefrontal cortex, hippocampus, and striatum. Furthermore, only PCPA treatment could eliminate loganin-induced antidepressant-like effects in TST. Loganin exerts antidepressant-like effect in the TST depending on 5-HT levels in the central nervous system, which provide a potential agent for depression therapy.

The aim of this study was to compare nasogastric (NG) feeding with nasojejunal (NJ) feeding when treating pediatric patients with acute pancreatitis (AP). We performed a single-center, prospective, randomized, active-controlled trial involving 77 pediatric patients with AP from April 2014 to December 2017. The patients were randomized into two groups: the NG tube feeding group (34 patients) and the NJ tube feeding group (33 patients). The primary outcome measures included the enteral nutrition intolerance, the length of tube feeding time, the recurrent pain of pancreatitis and complications. A total of 62 patients with AP (31 patients for each group) came into the final analysis. No differences were found in baseline characteristics, pediatric AP score and computed tomography severity score between the two groups. Three (9.7%) patients in the NG group and one (3.2%) patient in the NJ group developed intolerance (relative risk = 3.00, 95% confidence interval 0.33–27.29, P = 0.612). The tube feeding time and length of hospital stay of the NG group were significantly shorter than those of the NJ group (P = 0.016 and 0.027, respectively). No patient died in the trial. No significant differences were found in recurrent pain, complications, nutrition delivery efficacy, and side effects between the two groups. NG tube feeding appears to be effective and safe for acute pediatric pancreatitis compared with NJ tube feeding. In addition, high qualified, large sample sized, randomized controlled trials in pediatric population are needed.

Objectives Compared with other thyroid markers, fewer studies have explored the associations between triiodothyronine (T3), T3/free thyroxine (fT4) and glucose abnormality during pregnancy. Thus, we aimed to: (i) examine the associations of T3 and T3/fT4 with glucose metabolism indicators and (ii) evaluate, in the first trimester, the performance of the two markers as predictors of gestational diabetes mellitus (GDM) risk. Methods Longitudinal data from 2723 individuals, consisting of three repeated measurements of T3 and fT4, from the Man’anshan birth cohort study (MABC), China, were analyzed using a time-specific generalized estimating equation (GEE). The receiver operating characteristic curve (ROC) – area under the curve (AUC) and Hosmer–Lemeshow goodness of fit test was used to assess the discrimination and calibration of prediction models. Results T3 and T3/fT4 presented stable associations with the level of fasting glucose, glucose at 1h/2 h during pregnancy. T3 and T3/fT4 in both the first and second trimesters were positively associated with the risk of GDM, with the larger magnitude of association observed in the second trimester (odds ratio (OR) = 2.50, 95% CI = 1.95, 3.21 for T3; OR = 1.09, 95% CI = 1.07, 1.12 for T3/fT4). T3 ((AUC) = 0.726, 95% CI = 0.698, 0.754) and T3/fT4 (AUC = 0.724, 95% CI = 0.696, 0.753) in the first trimester could improve the performance of the prediction model; however, the overall performance is not good. Conclusion Significant and stable associations of T3, T3/fT4 and glucose metabolism indicators were documented. Both T3 and T3/fT4 improve the performance of the GDM predictive model.

Ischemic stroke (IS) accounts for most of the cases of stroke onset, and due to short therapeutic time window for thrombolysis and numerous limited treatment measures and contraindications, lots of patients cannot receive satisfying therapeutic effects resulting in high disability and mortality worldly. In recent years, extracellular vesicles (EVs), as nanosized membrane-structured vesicles secreted from almost all cells, especially from stem/progenitor cells, have been reported to exert significant beneficial effects on IS from multiple approaches and notably ameliorate neurological outcome. Moreover, based on nano-size and lipid bilayer structure, EVs can easily penetrate the blood-brain barrier and migrate into the brain. In this review, we mainly systematically summarize the therapeutic effects of EVs on IS and explore their potential applications. Simultaneously, we also discuss administration routines, dosages, experimental observation time, and some key issues of EV application during IS treatment. It contributes to a comprehensive understanding of the progress of EV treatment for IS and providing confident evidence for further EV clinical application widely.

Objective In the present study, we explored the clinical effect of midazolam as an adjuvant analgesic and tranquilizer after brachial plexus block anesthesia with the aid of imaging guidance. Methods We selected 106 patients who had undergone elective unilateral upper extremity surgery from January 2017 to December 2019 and randomly divided them into groups A and B, with 53 cases in each group. All the patients had undergone brachial plexus block anesthesia. Group A received imidazole-assisted sedation, and group B received fentanyl plus midazolam-assisted sedation. Under ultrasound-guided intermuscular sulcus brachial plexus block, we observed and recorded the ultrasound anatomical images before injection, including the distance from the lower edge of the upper, middle, and lower trunk of the forearm brachial plexus to the skin. We also recorded the anesthesia and operation times, effects of the anesthetic block, and incidence of adverse reactions. Results The distance from the lower edge of each nerve trunk to the skin averaged 1.002 cm for the upper stem, 1.598 cm for the middle stem, and 2.26 cm for the lower stem. The average anesthesia procedure time was 3 minutes, 56 seconds and was within 3–5 minutes for 92% of the procedures. The anesthesia effect was excellent, good, and poor in 81%, 11%, and 6%, respectively, and ineffective for 2% and effective for 92%. Conclusions The ultrasound-guided inferior intermuscular sulcus approach for brachial plexus block is suitable for unilateral upper extremity radial hand surgery. For surgery involving the upper extremity ulnar hand side, a larger dose (concentration) of local anesthetic should be used within a safe range and/or an additional ulnar nerve block might be necessary. Midazolam adjuvant medication can have a good sedative and amnestic effect in brachial plexus block anesthesia, helping to reduce pain and inhibit the increase in stress levels.

Facial thread-lifting (FTL) has gained more popularity, but the incidences of complications following FTL remain controversial. We aimed to perform a meta-analysis and systematic review to estimate the incidences of complications and to compare the short- and long-term satisfaction rates following FTL. We searched PubMed, Web of Science, Embase and Cochrane library for eligible studies. The primary outcome was the incidences of complications following FTL. The secondary outcome was the satisfaction rate immediately and 6-month after FTL. The pooled incidences of complications and 95% confidence intervals were estimated using random-effects models. A total of 26 studies were included in this meta-analysis. Swelling was the most commonly reported complication with a pooled incidence of 35%, followed by skin dimpling (10%), paresthesia (6%), thread visibility/palpability (4%), infection (2%), and thread extrusion (2%). Absorbable threads were associated with a significantly lower risk of paresthesia (3.1% vs. 11.7%) and thread extrusion (1.6% vs. 7.6%) than non-absorbable threads. Patients older than 50 years had a significantly higher risk of dimpling (16% vs. 5.6%) and infection (5.9% vs. 0.7%) than their younger counterparts. In addition, the pooled long-term satisfaction rate was significantly decreased compared to it immediately after FTL (88% vs. 98%). Non-absorbable threads and older age of patients are associated with higher risks of complications. Therefore, we recommend a judicious use of non-absorbable threads and FLT in older patients. Furthermore, it should be discussed with patients preoperatively that the rejuvenation effect of FTL may not maintain in the long-term. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Objectives Due to the impact of COVID‐19 epidemic, face‐to‐face follow‐up treatments for patients with chronic pain and implanted spinal cord stimulation (SCS) devices are forced to be delayed or stopped. This has led to more follow ups being done remotely. Meanwhile, with the development of 4G/5G networks, smartphones, and novel devices, remote programming has become possible. Here, we investigated the demand and utility of remote follow‐ups including remote programming for SCS for patients with chronic pain. Materials and Methods A questionnaire including questions on demographic characteristics, pain history, postimplantation life quality, standard follow‐up experience, remote follow‐up, and remote programming experience was sent to patients diagnosed as chronic intractable pain and treated with SCS during January 2019 to January 2020. Results A total of 64 participants completed the questionnaire. About 70% of participants expressed demands for remote follow‐ups due to the inconvenience, high costs, and time consumption of traditional follow‐up visits. Nearly 97% of participants have attempted remote follow‐ups, and about 81% of participants have further tried remote programming. Approximately, 96% of them recognized the benefits. Conclusions The remote programming was in high demand among participants. Most of the participants have tried remote follow‐ups or even remote programming. The remote programming appeared to be more efficient, economic and were widely recognized among participants.

Multispectral CT is a promising method in material characterization, nondestructive evaluation, and other applications. For multispectral CT, the method of projection domain separation can make multispectral CT reconstruction less complex and easier to implement. But X-ray spectrum should be known. By blind separation of projection sequences with different X-ray energy, the ray spectrum is not known in advance, and narrow-spectrum projections can be captured too. However, the proposed blind separation is a signal processing method, without energy constraint. The energy directivity and component characterization accuracy are weaker. To address this problem, this article uses X-ray basis-effect decomposition to propose a new separation model. Both simulation and actual samples are tested to verify and evaluate the proposed method. The experimental results show that the proposed separation model has stronger energy spectrum directivity. The reconstructed attenuation coefficient has smaller error and superior narrow-spectrum characteristics.

Background Facial thread-lifting (FTL) is a minimally invasive facial rejuvenation technique. However, to date, no study has focused on the treatment of complications associated with FTL. The purpose of this study was to report on clinical manifestations of complications following FTL and their treatment methods. Methods We retrospectively reviewed the electronic medical records of patients who presented with complications of FTL. Patient demographics, medical history, types and clinical manifestations of complications, imaging, treatment methods, histopathological findings, and follow-up information were collected. Descriptive statistical analysis was performed. Results Our sample included 61 patients, all women, with a mean age of 36.3 ± 8.9 years. The most common reason for consultation was infection (31.2%), followed by dissatisfaction with postoperative facial contour (23%), paresthesia (19.7%), dimpling and irregularity (16.4%), subcutaneous induration (13.1%), thread extrusion (4.9%), and facial nerve injury (3.3%). Fifty-one (83.6%) patients reported alleviated symptoms after receiving pharmaceutical and physical therapies. Surgical interventions, including debridement and thread removal, were required in 10 patients (16.4%). Threads were completely or partially removed in 5 patients within 3 months of the initial FTL. During a median follow-up of 1.7 years, 9 patients recovered well and were satisfied with the clinical outcomes, whereas one patient was unsatisfied due to dimpling and scarring. Conclusions The results show that most complications after FTL can be treated non-surgically. Revision surgery is recommended for patients with recurrent infection, thread extrusion, and subcutaneous induration. Aesthetic surgeons and dermatologists should comply with the indications for FTL and optimize surgical procedures to minimize the risk of complications.

The purpose of this study is to estimate the incidence of fixation-related complications following ultrasound-activated biodegradable osteosynthesis (UBO) in the treatment of craniosynostosis. The authors searched MEDLINE, PubMed, Embase, Google Scholar, and Cochrane Library from January 2005 to January 2020 for clinical studies reporting the use of UBO for fixation in the treatment of craniosynostosis. The primary outcome was the incidence of fixation-related complications, including unstable fixation; swelling, plate visibility, or palpability; infection; inflammation, sinus formation, and discharge; implant exposure; reoperation or implant removal. The pooled incidence rates were estimated using random-effects models. Of 155 studies identified, 10 were included, representing 371 patients. Forty-six (12.4%) patients presented fixation-related complications. The incidence rates of swelling/visibility/palpability, infection, and reoperation/implant removal were pooled based on the available data. The pooled incidence rate of chronic swelling/visibility/palpability was 0.21 (95% confidence interval [CI], 0.05-0.43). Sensitivity analysis by omitting the outlier study demonstrates that the incidence of swelling/visibility/palpability was 0.07 (95% CI, 0.04-0.11). The pooled incidence rate of infection and reoperation/implant removal was 0.07 (95% CI, 0.01-0.16) and 0.04 (95% CI, 0.01-0.09), respectively. Results show that although UBO can provide stable fixation, chronic swelling/visibility/palpability, infection, and reoperation for removal are not uncommon. Based on the literature, the authors recommend judicious use of UBO in patients with large frontorbital advancement and in the area of the coronal suture or other sites with thin overlying skin/subcutaneous tissue. The high possibility of chronic swelling/palpability/visibility during degradation, needs to be discussed preoperatively.

Schisandra chinensis (Turcz.) Baill., Schisandraceae, is a common Chinese traditional medicine for the treatment of nervous system disorders and cardiovascular diseases. However, little is known about its efficacy in treating gastrointestinal diseases. In the present study, the protective effect of the ethanol extract of S. chinensis against ethanol-induced acute gastric lesions was investigated in mice. Furthermore, we developed a method based on high-performance liquid chromatography for the quantification of bioactive lignans with a dibenzocyclooctadiene skeleton. The ethanol extract of S. chinensis significantly decreased the ulcer index, sheltered mucosa from lesions, increased levels of superoxide dismutase, decreased malondialdehyde levels, and downregulated plasma levels of tumor necrosis factor-α and interleukin-1β. Our findings demonstrated the gastroprotective properties of the ethanol extract of S. chinensis.

To balance the contradiction between the rapid growth of data service demands and the limited spectrum resources, wireless network virtualization (WNV) has been proposed as a promising technology by isolating and sharing wireless resources among different virtual networks in the future wireless networks. In this paper, a two-dimension-time-scale hierarchical resource allocation scheme is proposed in the multi-service wireless virtualized network, which consists of three 5G generic scenarios. The resource slicing problem is decomposed into two time scales including large time period for inter-slice resource pre-allocation and small time slot for intra-slice resource scheduling. In large time period, the inter-slice resource pre-allocation problem is formulated as a multi-objective optimization problem (MOOP) by modeling the packets arriving and serving process of each slice as a queueing system. While in small time slot, the resource block (RB) and power scheduling in each slice is formulated as a stochastic optimization problem considering dynamic traffic arrivals and time-varying channel conditions, which is aimed at optimizing the overall performance subject to various quality of service (QoS) requirements such as network stability, delay, reliability, transmission rate and power constraints. The stochastic optimization problem can be transformed into a delay-aware optimization problem by applying Lyapunov optimization technique, and be solved by the proposed algorithm consisting of a heuristic algorithm and a concave optimization algorithm. The simulation results show that the proposed schemes are close to the optimal solution with a lower complexity, which can also achieve a performance-delay tradeoff related to the control factor.

Childhood trauma (CT) is a well‐established risk factor for major depressive disorder (MDD). However, the underlying mechanism linking CT and MDD remains not fully understood. The present study tested the hypothesis that CT have effects on specific types of anhedonia in depression via reward system. To do so, we evaluated different aspects of anhedonia and resting‐state functional connectivity (FC) in reward system among 66 patients with MDD (44 with moderate‐to‐severe and 22 with no or low CT), and 57 healthy controls (HC; 23 with moderate‐to‐severe and 34 with no or low CT). Results showed that MDD patients with moderate‐to‐severe CT suffered more severe state anhedonic depression than patients with no or low level of CT. Individuals with moderate‐to‐severe CT, irrespective of MDD diagnosis, had elevated physical, social and anticipatory but not consummatory trait anhedonia, and demonstrated decreased left nucleus accumbens (NAcc)‐right orbital frontal cortex (OFC) and left ventral caudate‐left OFC connectivity compared to those with no or low exposure. Left NAcc‐right OFC connectivity mediated relationship between CT and state anhedonia in MDD. The total altered ventral striatum (VS)‐OFC connectivity mediated links between CT and physical trait anhedonia in HC. These findings highlight specific types of anhedonia and the core reward system as targets of CT. Blunted hedonic responses via decreased coupling within core reward system may be involved in the mechanism of depression following CT. Implications for clinical interventions are also discussed.

To satisfy the rapid growth of data service demands on the limited spectrum resources, wireless network virtualization (WNV) has been proposed as a promising technology in the future wireless networks. Meanwhile, Device-to-Device (D2D) communication, as an underlay to cellular networks, is also a proposed solution to promote the spectrum efficiency. However, it is a challenge to design an appropriate virtual resource slicing strategy among different wireless service providers in the two-tier LTE-D2D networks. In this paper, considering dynamic traffic arrivals and time-varying channel conditions, the virtualized resource management in the multi-service coexisting LTE-D2D networks is formulated into a multi-objective stochastic optimization problem. Leveraging on weighted Tchebycheff approach and Lyapunov optimization technique, the multi-objective stochastic optimization problem can be transformed into a delay-aware optimization problem, which is a mixed-integer nonlinear programming (MINLP) problem and can be transformed into a convex one by a series of reformulation. A distributed algorithm based on the alternating direction method of multipliers (ADMM) is proposed to obtain a close-to-optimal solution with a lower computational complexity. Finally, the simulation results show that the proposed scheme can achieve a performance-delay tradeoff related to the control factor $V$ with at most ${0.2}{\%}$ performance loss compared with the optimal solution.

Drugs that induce thrombosis in the tumour vasculature have not resulted in long-term tumour eradication owing to tumour regrowth from tissue in the surviving rim of the tumour, where tumour cells can derive nutrients from adjacent non-tumoral blood vessels and tissues. Here, we report the performance of a combination of tumour-infarction therapy and chemotherapy, delivered via chitosan-based nanoparticles decorated with a tumour-homing peptide targeting fibrin-fibronectin complexes overexpressed on tumour-vessel walls and in tumour stroma, and encapsulating the coagulation-inducing protease thrombin and the chemotherapeutic doxorubicin. Systemic administration of the nanoparticles into mice and rabbits bearing subcutaneous or orthotopic tumours resulted in higher tumour growth suppression and decreased tumour recurrence than nanoparticles delivering only thrombin or doxorubicin, with histological and haematological analyses indicating an absence of detectable toxicity. The co-administration of a cytotoxic payload and a protease to elicit vascular infarction in tumours with biodegradable tumour-targeted nanoparticles represents a promising strategy for improving the therapeutic index of coagulation-based tumour therapy.

In order to investigate the effects of unsteady aerodynamic loads on the driving safety and comfort of trains running on bridges, a three-dimensional and multi-body system model of train–track–bridge was established and the dynamic responses of the coupling system were calculated by combining the finite element software ANSYS with the multi-body dynamics software SIMPACK. The driving safety and comfort of a train running on a bridge under steady and unsteady aerodynamic loads were compared and analyzed. The effects of different crosswind speeds on the driving safety of the train running on the bridge under unsteady aerodynamic loads were studied. It is found that the index values of the driving safety and comfort of the train at the speed of 200–300 km/h without the wind loads are smaller (meaning safer) than those of the train under the wind loads. When the average speed of crosswind is 20 m/s, the driving safety assessment results of the train are better and its comfort assessment results are more conservative with considering the unsteady aerodynamic loads than the steady wind load case. When the average speed of crosswind is smaller than 10 m/s and the train speed is 250 km/h, the driving safety and comfort of the train on the bridge meet the requirements, and the level of stability can reach “good” or above. Through the analysis of driving safety of the train on the bridge under different crosswind speeds, the threshold values of safe driving were obtained, which can provide a better basis for the safe operation of trains on bridges.

Accurately quantifying the aerodynamic forces acting on vehicles and long-span bridges is critical for assessing the safety of moving vehicles on bridges which are subjected to strong wind. It is necessary to consider the aerodynamic interference between vehicles and the bridge, especially for this with the bluff body section and wind barriers. However, very few investigations have been carried out to find aerodynamic coefficients of vehicles on a bridge with the bluff body section and considering the effect of wind barrier. This article therefore carried out wind tunnel tests to determine aerodynamic coefficients of container truck on a bridge with a π-cross section and wind barriers. The influence of vehicle position in different road lanes of the bridge deck and the aerodynamic interference between vehicles on the aerodynamic characteristics of the vehicle and the bridge are investigated. Different heights and ventilation ratios of wind barrier are taken into consideration to examine variations of aerodynamic coefficients with different wind barriers. Furthermore, the change mechanism in the aerodynamic coefficients of the vehicles is observed by analyzing the wind pressure distribution on the surface of the vehicles. The test results show that the different lane locations of the vehicle affect the aerodynamic coefficients significantly, as well as the aerodynamic interference between vehicles with transverse arrangement or longitudinal arrangement, especially for the side force coefficient. The existence of wind barrier reduces the side force coefficients of the vehicle remarkably. Such effects also vary with the ventilation ratio and height of wind barrier.

Introduction Antimicrobial resistance (AMR) of Neisseria gonorrhoeae (N. gonorrhoeae) becomes a grave public health problem in the world. A strengthened Antimicrobial Resistance Surveillance Program is needed to track the trend of AMR development. However, the lack of a proper antimicrobial susceptibility test (AST) method is a barrier to expand the AMR surveillance in China. Traditional agar dilution (AD) method is laborious and E-test strips have no approval license for clinical use. Herein, a Chinese group modified the microdilution (MD) method for clinical ASTs. The objective of this study is to compare the MD method with the AD method for N. gonorrhoeae AST. Materials and methods A total of 166 clinical isolates were tested for antimicrobial susceptibility of ceftriaxone, spectinomycin, azithromycin, ciprofloxacin, tetracycline, and penicillin using MD and AD method simultaneously. Results of MD method were read manually or automatically. Rates of essential agreement (EA), category agreement (CA), minor error, and very major error were compared. Results The total EAs (compared with results read manually) of penicillin, tetracycline, ciprofloxacin, spectinomycin, ceftriaxone, and azithromycin were 90.4%, 97.0%, 85.5%, 100.0%, 94%, and 72.3%; and CAs were 82.5%, 94.0%, 100%, 100%, 95.2%, and 94%, respectively. Conclusion We conclude that the MD method might be an alternative for clinical AST of N. gonorrhoeae in China. In particular, MD method has the potency of accurate differentiation of isolates resistant to ceftriaxone or azithromycin, which were empirically recommended for gonococcal treatment, but its quality remained suboptimal, and further improvement is needed for clinical use.

The purpose of this retrospective cohort study was to identify the independent risk factors for long-term skeletal relapse following mandibular advancement with bilateral sagittal split osteotomy. Univariate and multivariate linear regression analyses were performed including nine common risk factors for relapse as independent variables and horizontal/vertical long-term (≥2 years) skeletal relapse as dependent variables. Ninety-six patients were analyzed; 66 were female (68.8%) and the average age of the patients was 29.7 ± 10.5 years. Over an average follow-up of 3.8 ± 1.8 years after an initial mandibular advancement of 8.8 ± 2.4 mm, long-term skeletal relapse of 1.6 ± 1.0 mm horizontal and 0.9 ± 0.7 mm vertical was found. Multivariate analysis identified age, preoperative mandibular plane angle (MPA), bimaxillary surgery, counterclockwise mandibular rotation, and the magnitude of mandibular advancement to be significantly associated with horizontal long-term skeletal relapse. Preoperative MPA, counterclockwise mandibular rotation, and the magnitude of mandibular advancement were significantly associated with vertical long-term skeletal relapse. Thus preoperative MPA, the magnitude of mandibular advancement, and counterclockwise mandibular rotation of the mandible were found to be independent risk factors for both horizontal and vertical long-term skeletal relapse. Although long-term skeletal relapse cannot be avoided entirely, understanding the independent risk factors and their contributions will optimize treatment planning and long-term stability.

Background Trauma can cause large defects in the weight-bearing foot sole. The reconstruction of such defects poses a major challenge in providing a flap that is durable, sensate, and stable. The pedicled medial plantar flap has been commonly used for reconstructing heel and plantar forefoot defects; however, the ipsilateral instep region is usually compromised by trauma. The purpose of this article was to report the use of contralateral free medial plantar flaps for the coverage of weight-bearing plantar defects and to compare these with distant free flaps. Methods Between 2005 and 2019, 15 patients (10 men and 5 women) with weight-bearing foot plantar defects were treated with a contralateral medial plantar flap, 11 (7 men and 4 women) with either a latissimus dorsi flap or a scapular flap. The average age was 18.07 ± 10.14 years (range, 4-34 years) and 26.55 ± 13.05 years (range, 13-56 years), respectively. Surgery was performed as a primary or secondary reconstruction after a trauma by the same surgical team. Results The mean size of defects was 9.73 ± 3.55 × 6.43 ± 2.8 cm in the contralateral free medial plantar flap group and 17.14 ± 6.84 × 11.41 ± 4.29 cm in the free dorsal flap group. All flaps survived in both groups. In the instep flap group, the appearance was satisfactory, the flap was durable, and tactile sensation was preserved in all patients, and none required a revision procedure. Two patients experienced delayed union of the donor-site grafted skin. In the dorsal flap group, 5 patients complained of a partial necrosis or delayed union at the recipient site, and 9 developed recurrent ulcerations over the weight-\bearing area. Five patients achieved only partial sensation in the flap. Conclusions The contralateral medial plantar flap provides superior appearance, duration, and sensation over distant muscle flaps, without recurrent ulcerations. However, dorsal myocutaneous flaps may be used as a substitute when the defects are beyond the maximum boundaries of the instep area or are combined with bone loss.

The measurement and control of high temperature play very important roles in national defense, military, scientific experiments, industrial and agricultural production. Photoelectric pyrometer is one of the important radiation thermometers for non-contact temperature measurement. It has an important application in the field of high temperature measurement, and its performance directly affects the accuracy of temperature measurement. By improving the design of the detection optical system of the photoelectric pyrometer, the imaging performance of the photoelectric pyrometer can be improved effectively, and the temperature measurement accuracy can be improved. In this paper, the temperature measurement principle of photoelectric pyrometer, the working principle of the detection optical system and the composition of the system are introduced. The optical components that affect the imaging of the optical system of the photoelectric pyrometer are analyzed. The optical pyrometer detection optical system is simulated by ZEMAX software, based on the analysis results, the Modulation Transfer Function (MTF) and the spot Diagram are used as the main evaluation criteria to optimize the design of the objective lens of the photoelectric pyrometer detection optical system. The imaging performance of the photoelectric pyrometer detection optical system and the accuracy of temperature measurement of the photoelectric pyrometer are improved by optimization design of the detection optical system.

This study sought to answer the following question: Do patients with different mandibular plane angles (MPAs) have a different time to relapse after mandibular advancement with bilateral sagittal split osteotomy?We performed a retrospective cohort study of patients who underwent bilateral sagittal split osteotomy advancement at Massachusetts General Hospital between 2005 and 2017. The primary predictor variable was MPA, categorized as low (25°), medium (between 25° and 35°), or high (35°). The outcome variable was time to relapse (≥2-mm posterior change at the B point). Other covariates included gender, age, temporomandibular joint symptoms, bimaxillary surgery, direction of mandibular rotation, magnitude of advancement, genioplasty, and fixation method. Time to relapse was estimated using the Kaplan-Meier method. Cox and parametric regressions for interval-censored data were performed. P .05 was considered statistically significant.The sample was composed of 58 patients (40 female patients), with a mean age of 26.1 ± 4.9 years, grouped as follows: low MPA, n = 15; medium MPA, n = 26; and high MPA, n = 17. Clinically significant relapse was found in 18 patients (31%). Age, temporomandibular joint symptoms, counterclockwise rotation, and magnitude of advancement were statistically significantly different among the 3 groups. When we assessed time to relapse, the Kaplan-Meier method showed that high-MPA patients had a longer mean time at risk and higher estimated probabilities of relapse at different time points compared with low- and medium-MPA patients (P .05). However, this association was not significant in Cox and parametric regressions.Our results suggest that clinically significant relapse was found during the first postoperative year in low-MPA patients and from 2 to 5 years postoperatively in high-MPA patients. Multivariate regression analyses did not show a significant association between MPA and time to relapse, suggesting that other covariates may play a role in the observed time to relapse.

The aim of this study was to identify interaction effects among risk factors for long-term skeletal relapse. The study sample consisted of 96 patients who underwent mandibular advancement with bilateral sagittal split osteotomy. Ten predictor variables were analyzed for an interaction effect: sex, age, preoperative temporomandibular joint symptoms, mandibular plane angle (MPA), single or double jaw surgery, clockwise or counterclockwise mandibular rotation, magnitude of mandibular advancement, concomitant genioplasty, type of fixation, and follow-up duration. Modeling interactions between pairs of covariates were applied to detect a significant interaction among these risk factors on horizontal and vertical long-term skeletal relapse, respectively. Stratification analyses and two-way full factorial interaction analyses were performed to demonstrate how the interaction influenced the associations between covariates and relapse. The interactions between sex and mandibular rotation (P=0.006) and between MPA and mandibular rotation (P=0.002) were statistically significant for horizontal long-term skeletal relapse. No significant interaction was identified for vertical relapse. This study showed that female patients and those with an MPA ≥30° undergoing counterclockwise mandibular rotation are predisposed to greater horizontal long-term skeletal relapse. Therefore, the judicious use of counterclockwise rotation is recommended in order to minimize the relapse, especially in female patients and those with a high MPA.

Aimed at identifying the health state of wind turbines accurately by comprehensively using the change information in spatial and temporal scale of the supervisory control and data acquisition (SCADA) data, a novel condition monitoring method of wind turbines based on spatio-temporal features fusion of SCADA data by convolutional neural networks (CNN) and gated recurrent unit (GRU) was proposed in this paper. First, missing value complement and selection of variables with Pearson prod-moment correlation coefficient were applied to improve the effectiveness of SCADA data. Second, a deep learning model was constructed by the structures of CNN and GRU. The spatial features in SCADA data were extracted by CNN at every step, and the temporal features in the sequence of spatial features were extracted and fused by GRU. Third, the historical healthy SCADA data was used to train the normal behavior model. At last, the trained model received measured data and output the predicted values. The entire residual between the actual data and the predicted output was calculated to put into the exponential weighted moving average control chart for recognizing the condition of the wind turbine. The effectiveness and availability of the proposed method were proved in measured SCADA data experiments.

Context: Alzheimer’s disease (AD) is a chronic neurodegenerative disease that originates from central nervous system lesions or recessions. Current estimates suggest that this disease affects over 35 million people worldwide. However, lacking effective drugs is the biggest handicap in treating AD. In traditional Chinese medicine (TCM), Polygala tenuifolia Willd. (Polygalaceae) is generally used to treat insomnia, memory dysfunction and neurasthenia. Objective: This review article explores the role of P. tenuifolia and its active components in anti-Alzheimer’s disease. Methods: Literature for the last ten years was obtained through a search on PubMed, SciFinder, CNKI, Google Scholar, Web of Science, Science Direct and China Knowledge Resource Integrated with the following keywords: Polygala tenuifolia, polygalasaponin XXXII (PGS 32), tenuifolin, polygalacic acid, senegenin, tenuigenin, Alzheimer’s disease. Results: Polygala tenuifolia and its active components have multiplex neuroprotective potential associated with AD, such as anti-Aβ aggregation, anti-Tau protein, anti-inflammation, antioxidant, anti-neuronal apoptosis, enhancing central cholinergic system and promote neuronal proliferation. Conclusions: Polygala tenuifolia and its active components exhibit multiple neuroprotective effects. Hence, P. tenuifolia is a potential drug against Alzheimer’s disease, especially in terms of prevention.

Objective Anti-Müllerian hormone (AMH) is recognized as the most important biomarker for ovarian reserve. In this cross-sectional study, we aimed to explore the potential association of AMH with central obesity or general obesity in women with polycystic ovary syndrome (PCOS). Methods In this cross-sectional study, 179 patients with PCOS were enrolled and underwent anthropometric measurements (BMI and waist circumference (WC)) and serum AMH level detection. Pearson’s correlation and multivariable logistic regression analyses were performed to determine the associations of AMH with central obesity and general obesity. Results Subjects with increasing BMI showed significantly lower values of AMH (median (interquartile range (IQR)) 8.95 (6.03–13.60) ng/mL in normal weight group, 6.57 (4.18–8.77) ng/mL in overweight group, and 6.03 (4.34–9.44) ng/mL in obesity group, P = 0.001), but higher levels of systolic blood pressure, fasting insulin, total cholesterol, triglycerides, LDL-c, obesity indices (WC, hip circumferences, waist-to-hip ratio, waist-to-height ratio (WHtR), and Chinese visceral adiposity index (CVAI)). Compared with the group of PCOS women without central obesity, the group with central obesity had significantly lower value of AMH (median (IQR) 8.56 (5.29–12.96) ng/mL vs 6.22 (4.33–8.82) ng/mL; P = 0.003). Pearson’s correlation analysis showed that AMH was significantly and negatively correlated with BMI (r = −0.280; P < 0.001), WC (r = −0.263; P < 0.001), WHtR (r = −0.273; P < 0.001), and CVAI (r = −0.211; P = 0.006). Multivariate logistic regression analysis with adjustment for potential confounding factors showed that AMH was independently and negatively associated with central obesity but was not significantly associated with general obesity. Conclusions AMH was independently and negatively associated with central obesity. Closely monitoring the WC and AMH should be addressed in terms of assessing ovarian reserve in women with PCOS.

BackgroundChlamydia trachomatis(CT) infection is one of the most pervasive sexually transmitted infections and has high prevalence in urogenital and extra-urogenital sites among men who have sex with men (MSM). This study investigated anatomical site-specific prevalence and genotypes of CT among MSM recruited from three geographic areas in China.MethodsWe collected urine specimens and anorectal, pharyngeal swab specimens from 379 MSM. CT infection was identified using polymerase chain reaction and CT genotyping was determined by sequences of the ompA gene.ResultsThe results indicated that the overall prevalence of CT infection was 18.2% (95% confidence intervals [CIs], 13.9–22.5%) and significantly different between the cities (p = 0.048). The infection was most common at the anorectal site (15.6, 95%CIs 11.6–19.5%) followed by urethral (3.2, 95%CIs 1.4–5.0%) and oropharyngeal sites (1.6, 95%CIs 0.3–2.9%). Genotypes D and G were the most common CT strains in this population but genotype D was significantly predominated in Nanjing while genotype G was in Wuhan. No genotype related to lymphogranuloma venereum was found. CT infection was significantly related to the infection ofNeisseria gonorrhoeae(adjusted odds ratio [aOR] 14.27, 95%CIs 6.02–33.83,p p = 0.03).ConclusionThe high CT infection prevalence, particularly in the anorectal site, among MSM suggests the necessity to development an integrated CT screening and treatment program specifically focusing on this high-risk population. Surveillance of CT infections should be improved by including both infection and genotype based surveys into the current surveillance programs in China.

Skin cutaneous melanoma (SKCM) is one of the most malignant skin cancers and remains a health concern worldwide. Pyroptosis is a newly recognized form of programmed cell death and plays a vital role in cancer progression. We aim to construct a prognostic model for SKCM patients based on pyroptosis-related genes (PRGs). SKCM patients from The Cancer Genome Atlas (TCGA) were divided into training and validation cohorts. We used GSE65904 downloaded from GEO database as an external validation cohort. We performed Cox regression and the least absolute shrinkage and selection operator (LASSO) regression to identify prognostic genes and built a risk score. Patients were divided into high- and low-risk groups based on the risk score. Differently expressed genes (DEGs), immune cell infiltration and immune-related pathways activation were compared between the two groups. We established a model containing 4 PRGs, i.e., GSDMA, GSDMC, AIM2 and NOD2. The overall survival (OS) time was significantly different between the 2 groups. The risk score was an independent predictor for prognosis in both the uni- and multi-variable Cox regressions. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) analyses showed that DEGs were enriched in immune-related pathways. Most types of immune cells were highly expressed in the low risk group. All immune pathways were significantly up-regulated in the low-risk group. In addition, low-risk patients had a better response to immune checkpoint inhibitors. Our novel pyroptosis-related gene signature could predict the prognosis of SKCM patients and their response to immune checkpoint inhibitors.

The quality of life and survival rates of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD–PAH) have been greatly improved by defect-repair surgery and personalized treatments. However, those who survive surgery may remain at risk of persistent PAH, the prognosis may be considerably worse than those unoperated. Dynamic monitoring of clinical measures during the perioperative period of shunt correction is therefore indispensable and of great value. In this study, we explored the plasma-metabolite profiling in 13 patients with CHD–PAH during the perioperative period of defect repair. Plasma was harvested at four time points: prior to cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. Untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. A total of 193 distinguishing metabolites were determined at different time points, enriched in pathways such as oxidation of branched-chain fatty acids. We found that 17 metabolite alterations were significantly correlated with the reduction in mean pulmonary arterial pressure (MPAP) at T48 versus Pre. Gradients in diastolic pulmonary arterial pressure (DPAP), bicarbonate in radial artery (aHCO(3)), bicarbonate in superior vena cava (svcHCO(3)), and the partial pressure of dissolved CO(2) gas in radial artery (aPCO(2)) were positively correlated with MPAP gradient. Notably, these clinical-measure gradients were correlated with alterations in shunt-correction-associated metabolites. In total, 12 out of 17 identified metabolites in response to defect repair were increased at both T24 and T48 (all P

WHAT IS KNOWN AND OBJECTIVES Dapagliflozin was the first oral treatment approved in type 1 diabetes mellitus (T1DM) patients, simultaneously improving body weight. However, the time course and dose effect of dapagliflozin on loss of weight in T1DM patients was still unknown. The present study aimed to investigate quantitative relationship between dapagliflozin and loss of weight in T1DM patients based on Model-based Meta-analysis. METHODS Five dapagliflozin dosage groups, two of them were 5 mg/day and three of them were 10 mg/day, 1612 T1DM patients were analysed with maximal effect (Emax ) model, and evaluation index was change rate of body weight from baseline value. RESULTS In these T1DM patients, dosages were not incorporated into model, indicating no significant dose-response relationship between 5 and 10 mg/day affecting loss of weight. Emax and the treatment duration to reach half of the maximal effects (ET50 ) of dapagliflozin influencing loss of weight in T1DM patients were -4.9% and 10.4 weeks, and the duration to achieve 25%, 50%, 75%, and 80% (plateau) of Emax were 3.5, 10.4, 31.2, and 41.6 weeks. WHAT IS NEW AND CONCLUSIONS It was the first time to explore quantitative relationship between dapagliflozin and loss of weight in T1DM patients. To achieve the plateau period in loss of weight, 5 mg/day dapagliflozin was required for at least 41.6 weeks.

BackgroundPremature/low-birth-weight infants are at significant risk of metabolic diseases in adulthood, which may be related to the levels of fetal adipokine. Here, we investigated the differences in the levels of umbilical cord blood adiponectin, leptin, insulin, and ghrelin in preterm and term infants and sought to elucidate the link between these hormones and fetal growth. We also evaluated the interrelationship among these metabolic hormones in both groups of newborns.MethodsA total of 149 mother–infant pairs (100 in the preterm group and 49 in the term group) were enrolled in the study. The preterm group was further subdivided according to birth weight (≤1,500, 1,501–2,000, 2,001–2,500, and >2,500 g), gestational age (vs. ≥34 weeks), and appropriate for gestational age (AGA) vs. small for gestational age (SGA). The general condition of the mothers and the growth parameters of the newborns at birth were recorded.ResultsThe levels of adiponectin, leptin, and ghrelin were lower in the preterm group than those in the term group (p < 0.05). In the preterm group, the leptin levels of infants with gestational age ≥34 weeks were significantly higher than those of infants with gestational age vs. 0.36 ng/ml, p = 0.009). The levels of adiponectin were lower in the SGA group than those in the AGA group (mean ln adiponectin = 2.26 vs. 2.84 µg/ml, p = 0.001), whereas those of ghrelin displayed the opposite trend (mean ln ghrelin = 6.29 vs. 5.71 pg/ml, p < 0.001). Leptin was significantly correlated with insulin both in preterm infants with birth weight (BW) >2,000 g and in term infants. Umbilical cord blood leptin was positively correlated with the BW, birth length, and head circumference of newborns (r = 0.460, 0.311, and 0.310, respectively, all p < 0.05), whereas ghrelin was negatively correlated with the same parameters (r = −0.372, −0.415, and −0.373, respectively, all p > 0.05).ConclusionsThe lack of maturation of adipose tissue and the gastrointestinal tract by the fetus due to prematurity is associated with changes in the levels of cord blood adiponectin, leptin, and ghrelin. The dysregulation of these hormones in preterm infants may be a risk factor for fetal growth and future metabolic diseases.

In this study, the influences of wind barriers on the aerodynamic characteristics of trains (e.g. a CRH2 train) on a highway-railway one-story bridge were investigated by using wind pressure measurement tests, and a reduction factor of overturning moment coefficients was analyzed for trains under wind barriers. Subsequently, based on a joint simulation employing SIMPACK and ANSYS, a wind–train–track–bridge system coupled vibration model was established, and the safety and comfort indexes of trains on the bridge were studied under different wind barrier parameters. The results show that the mean wind pressures and fluctuating wind pressures on the trains’ surface decrease generally if wind barriers are used. As a result, the dynamic responses of the trains also decrease in the whole process of crossing the bridge. Of particular note, the rate of the wheel load reductions and lateral wheel-axle forces can change from unsafe states to relative safe states due to the wind barriers. The influence of the porosity of the wind barriers on the mean wind pressures and fluctuating wind pressures on the windward sides and near the top corner surfaces of the trains are significantly greater than the influence from the height of the wind barriers. Within a certain range, decreasing the wind barrier porosities and increasing the wind barrier heights will significantly reduce the safety and comfort index values of trains on the bridge. It is found that when the porosity of the wind barrier is 40%, the optimal height of the wind barrier is determined as approximately 3.5[Formula: see text]m. At this height, the trains on the bridges are safer and run more smoothly and comfortably. Besides, through the dynamic response analysis of the wind–train–track–bridge system, it is found that the installation of wind barriers in cases with high wind speeds (30[Formula: see text]m/s) may have an adverse effect on the vertical vibration of the train–track–bridge system.

BackgroundGlioblastoma (GBM) is the most common primary intracranial tumor and originates from the small pool of adult neural stem and progenitor cells (NSPCs). According to the World Health Organization (WHO) classification of brain tumors, gliomas are classified into grades I–IV, and GBM is defined as the highest grade (IV). GBM can be disseminated by cerebrospinal fluid (CSF), but extracranial metastasis is rare. Additionally, the pathway and mechanism involved remain unclear.Case PresentationWe report a rare case of left temporal lobe GBM with multiple bone metastases and soft tissue metastasis. This 49-year-old right-handed man who was diagnosed with GBM underwent surgery on May 9, 2017, followed by radiochemotherapy in June 2017. On August 13, 2019, local relapse was found. Then, the patient received a second surgery but not radiochemotherapy. In November 2019, the patient was reported to be suffering from low back pain for nearly 1 month. On December 6, 2019, magnetic resonance imaging (MRI) of the thoracolumbar vertebrae and abdominal computed tomography (CT) confirmed metastases on the ninth posterior rib on the right, the third anterior rib on the left, and the T7 and T10 vertebrae and their appendages. CT-guided rib space-occupying puncture biopsy was performed, and GBM was identified by pathology.ConclusionWe should pay attention to extracranial metastasis of GBM. Timely detection and early treatment improve overall quality of patients’ life. The extracranial metastasis in this patient may have occurred through the spinal nerve root or intercostal nerve. Further clinical observations are required to clarify the pathway and mechanism involved.

Background Although external circular frame (ECF) has been widely used for the correction of knee and ankle deformities, few studies reported the use of ECF for the treatment of severe postburn elbow contracture and stiffness (SPECS). The purpose of this retrospective study was to investigate the effectiveness and safety of the distraction using ECF in treating SPECS. Methods After institutional review board approval, we implemented a retrospective single-center case series study composed of consecutive patients treated for SPECS at Chinese PLA General Hospital between January 2010 and January 2018. After scar release and skin grafting, distraction with ECF was performed for 4 to 6 weeks, and the frame was retained for 2 more weeks before removal. Four weeks of splinting and at least 1 year of rehabilitation were recommended. Patient demographics, active and passive range of motion (ROM) of the elbow at different time points (preoperative, postdistraction, and final follow-up), and complications were collected from the electronic medical record. The primary outcome was the long-term improvement of the ROM. Other outcomes included complications and recurrence. Results The ECF was used to treat SPECS in 6 patients (3 males and 3 females, average age of 11.7 ± 2.6 years). Scar release and distraction with ECF significantly increased both active (from 3° preoperative to 38.7° postdistraction) and passive (from 3.5° preoperative to 48.3° postdistraction) ROM over an average distraction duration of 5.2 weeks. The long-term improvement of active and passive ROM was 38° ± 13.4° and 46° ± 14.7°, respectively, over a median follow-up of 4.1 years. Pin-tract infection occurred in 2 patients and were treated with local wound care and oral antibiotics. A tendon readhesion developed in 1 of the 6 patients because of noncompliance with splinting and physiotherapy, and was treated with revision surgery. Conclusions The 3C strategy (i.e., contracture release, coverage of the defect with skin grafting, and correction of articular angle with gradual distraction using the ECF) is able to increase the ROM with minor complications. We recommend distraction with ECF as part of the treatment arsenal, particularly for severe contractures in which 1-stage correction is unfeasible because of considerable soft tissue shortening.

Background: Neisseria gonorrhoeae (N. gonorrhoeae) is now recognized as a commonly reported sexually transmitted pathogen, and the increasing drug resistance of N. gonorrhoeae has become a serious public health problem. The accuracy of molecular detection for detecting moderate-level azithromycin resistance is not well-established. We summarized the data from studies of the N. gonorrhoeae 23S rRNA mutation at position 2611 with azithromycin resistance to determine the relationship between the mutation and resistance. Methods and Findings: In this systematic review and meta-analysis, two researchers independently searched six databases for studies with data for the azithromycin minimum inhibitory concentrations (MICs) and the 23S rRNA mutation C2611T of each N. gonorrhoeae isolate. Since the breakpoint of moderate-level resistance to azithromycin (ML-AzmR) was not determined, we divided the moderate level into two groups according to the range of MICs (moderate resistance limited to 2–128 mg/L or 4–128 mg/L) for data extraction. A random-effects model was used to calculate the pooled sensitivity rate, the specificity rate, the pooled positive likelihood ratio (PLR), the negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR). Meta-regression analyses by detection method, isolates sampling (a random sample or not), location, and sample size were performed to explore the possible causes of heterogeneity. The potential publication bias of the included studies was conducted by the Deeks’ test. We included 20 studies in our study: 20 studies have data of N. gonorrhoeae with MICs between 2 and 128 mg/L with mutation or without mutation at position 2611(4759 samples), and 14 studies have data of N. gonorrhoeae with MICs between 4 and 128 mg/L (3367 samples). In the group with the moderate level of 2–128 mg/L, the pooled sensitivity rate of the molecular assays was determined to be 71.9% (95% CI, 67.6–74%), the pooled specificity rate was 98.7% (95% CI, 98.2–99.0%), and the DOR ranged from 55.0 to 351.3 (mean, 139.1). In the 4–128 mg/L group, the pooled sensitivity rate was 91.9% (95% CI, 88.9–94.2%), the pooled specificity rate was 95.9% (95% CI, 95.1–96.6%), and the DOR ranged from 41.9 to 364.1 (mean, 123.6). Conclusion: Through this meta-analysis, we found that the C2611T mutation of 23S rRNA is valuable for the molecular diagnostic of moderate-level azithromycin resistance (ML-AzmR) in N. gonorrhoeae, especially when the moderate level is set at 4–128 mg/L. This rapid molecular detection method can be used for the rapid identification of ML-AzmR isolates in the clinic.

Background Management of cranial defects following failed cranioplasty due to titanium mesh exposure and infection is challenging. The purpose of this report is to describe a modified technique using a free myocutaneous flap transfer for primary soft tissue reconstruction, and titanium mesh reinsertion for cranioplasty revision. Methods Nineteen patients with titanium mesh exposure and infection following cranioplasty were treated from January 2012 to January 2019. The average patient age was 41.89 years and the average size of the cranial defect was 7.74 × 13.92 cm. The reasons for craniotomy were craniocerebral trauma (n = 17), cerebrovascular disease (n = 1), and brain tumor (n = 1). The mean duration between implant exposure and current procedure was 7.16 months. Implant was removed and a free myocutaneous flap was designed to cover both scalp and cranium defects. After a mean duration of 12.32 months, implants were re-inserted in a vascularized pocket at the second stage by elevating a plane between the previously transferred fascia layer and muscle layer. Results The average sizes of the muscle flaps and skin paddles were 7.74 × 13.92 cm and 4.97 × 8.97 cm. The average size of the implants was 8.24 × 14.42 cm. All flaps survived completely with no complication. After an average follow-up of 48.16 months there were no cranioplasty failures. Functional coverage of craniectomy defect sites with normalized head contour was achieved. Conclusions The use of free myocutaneous flap and implant reinsertion achieved durable cranial and scalp defect reconstruction and aesthetic outcomes. The myocutaneous flap increases blood supply to the scalp, which may reduce the chances of infection and implant re-exposure.

More clinical evidence is needed regarding the ranking priority of interventions for ALK-positive, brain metastatic (BM) non-small cell lung cancer (NSCLC). Eligible randomized controlled trials (RCTs) were identified. Progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) for the intended populations were analyzed with random effects, Bayesian network meta-analysis with the estimated hazard ratio (HR) and odds ratio (OR) with 95% credible interval (95% CrIs). We included 11 RCTs (2687 NSCLC and 991 BM patients) investigating 7 treatments and 5 medication classes. For PFS for BM patients, lorlatinib (hazard ratio (HR): 0.01, 95% CrI: 0.001-0.12), alectinib (HR: 0.05, 95% CrI: 0.01-0.21) and brigatinib (HR: 0.07, 95% CrI: 0.007-0.76) were top-ranking individual treatments; for ORR for BM patients, brigatinib, lorlatinib and alectinib were top-ranking treatments. For PFS for all NSCLC patients, the top-ranking individual treatments were lorlatinib (HR: 0.05, 95% CrI: 0.02-0.13), alectinib (HR: 0.09, 95% CrI: 0.05-0.18) and brigatinib (HR: 0.11, 95% CrI: 0.05-0.28). For OS for all NSCLC patients, we found that no individual treatments were superior to chemotherapy, whereas the following top-ranking interventions were alectinib (HR: 0.29, 95% CrI: 0.03-1.68), lorlatinib (HR: 0.41, 95% CrI: 0.04-4.13), and ceritinib (HR: 0.63, 95% CrI: 0.10-4.25). The results of individual treatments and medication classes were similar. Data were limited in regard to subgroup analyses and adverse events of BM patients. Lorlatinib has the most statistical superiority for BM patients, but ORR differences between third- and second-generation inhibitors are not obvious. All things considered, alectinib is recommended as first-line treatment, followed by lorlatinib, especially after developing drug resistance to alectinib.