Comparison of fascia iliaca block with quadratus lumborum block for hip arthroplasty: A meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of fascia iliaca block (FIB) versus quadratus lumborum block (QLB) remains controversial for pain management of hip arthroplasty. We conduct a systematic review and meta-analysis to explore the influence of FIB versus QLB on the postoperative pain intensity of hip arthroplasty. METHODS: We have searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane Library databases through July 2023 for randomized controlled trials assessing the effect of FIB versus QLB on pain control of hip arthroplasty. This meta-analysis is performed using the random-effect model or fixed-effect model based on the heterogeneity. RESULTS: Four randomized controlled trials and 234 patients were included in the meta-analysis. Overall, compared with QLB for hip arthroscopy, FIB was associated with substantially lower pain scores at 2 hours (mean difference [MD] = -0.49; 95% CI = -0.63 to -0.35; P < .00001) and pain scores at 12 hours (MD = -0.81; 95% CI = -1.36 to -0.26; P = .004), but showed no impact on pain scores at 24 hours (MD = -0.21; 95% CI = -0.57 to 0.15; P = .25), time to first rescue analgesia (standard mean difference = 0.70; 95% CI = -0.59 to 1.99; P = .29), analgesic consumption (MD = -4.80; 95% CI = -16.57 to 6.97; P = .42), or nausea and vomiting (odd ratio = 0.66; 95% CI = 0.32-1.35; P = .25). CONCLUSIONS: FIB may be better than QLB for pain control after hip arthroplasty, as evidenced by the lower pain scores at 2 and 24 hours.

Predictive value of combination of lung injury prediction score and receptor for advanced glycation end­products for the occurrence of acute respiratory distress syndrome.

The present study evaluated the predictive value of the combination of the lung injury prediction score (LIPS) and receptor for advanced glycation end-products (RAGE) for the occurrence of acute respiratory distress syndrome (ARDS) in critically ill patients with ARDS risk factors. A total of 551 patients with risk factors of ARDS were divided into an ARDS group and a non-ARDS group. LIPS was computed within 6 h of admission into the ICU, and the plasma concentration of RAGE was detected within 24 h of admission. Multivariate analysis was performed to identify independent associations, and the predictive values for ARDS occurrence were assessed with receiver operating characteristic (ROC) curve. Within 7 days after admission into the ICU, ARDS occurred in 176 patients (31.9%). Multivariate analysis demonstrated that LIPS [odds ratio (OR), 1.282; 95% confidence interval (CI), 1.108-1.604], RAGE levels (OR, 2.359; 95% CI, 1.351-4.813) and Acute Physiology and Chronic Health Evaluation II score (OR, 1.167; 95% CI, 1.074-1.485) were independently associated with ARDS occurrence. ROC curves demonstrated that the area under curve (AUC) of LIPS, RAGE levels and their combination was 0.714 [standard error (SE), 0.023; 95% CI, 0.670-0.759], 0.709 (SE, 0.025; 95% CI, 0.660-0.758) and 0.889 (SE, 0.014; 95% CI, 0.861-0.917), respectively. The AUC of LIPS combined with RAGE levels was significantly higher compared with those of LIPS (0.889 vs. 0.714; Z=6.499; P<0.001) and RAGE (0.889 vs. 0.709; Z=6.282; P<0.001) levels alone. In conclusion, both LIPS and RAGE levels were independently associated with ARDS occurrence in critically ill patients with ARDS risk factors, and had medium predictive values for ARDS occurrence. Combination of LIPS with RAGE levels increased the predictive value for ARDS occurrence.

Autoimmune congenital heart block: a case report and review of the literature related to pathogenesis and pregnancy management.

Autoimmune congenital heart block (ACHB) is a passively acquired immune-mediated disease characterized by the presence of maternal antibodies against components of the Ro/SSA and La/SSB ribonucleoprotein complex that mainly affects the cardiac conducting system. ACHB occurs in 2% of women with positive anti-Ro/SSA and anti-La/SSB antibodies and causes a high risk of intrauterine fetal death, neonatal mortality, and long-term sequelae. In this review, we first describe a case of ACHB to provide preliminary knowledge. Then, we discuss the possible pathogenic mechanisms of ACHB; summarize the pregnancy management of patients with positive anti-Ro/SSA and anti-La/SSB antibodies and/or rheumatic diseases, the prevention of ACHB, and the treatment of ACHB fetuses; and propose routine screening of these antibodies for the general population. Careful follow-up, which consists of monitoring the fetal heart rate, is feasible and reassuring for pregnant women with positive anti-Ro/SSA and/or anti-La/SSB antibodies to lower the risk of ACHB in fetuses. Moreover, maternal administration of hydroxychloroquine may be useful in preventing ACHB in pregnant women with anti-Ro/SSA and/or anti-La/SSB antibodies.

Anti-atopic dermatitis effect of fraxinellone via inhibiting IL-31 in vivo and in vitro.

Chronic recurrent itch and skin inflammation are prominent features of atopic dermatitis (AD), which is closely related to the immune response driven by T-helper type 2 (Th2) cells. The expression of interleukin 31 (IL-31) is positively correlated with the severity of dermatitis. Anti-IL-31 receptor α (IL-31RA) targeted drugs have been used to treat AD, however, they are expensive and have side effects. Fraxinellone (FRA) is one of the main limonoid components in the dried root bark of Dictamnus dasycarpus Turcz.; however, its anti-inflammatory and antipruritic effects on atopic dermatitis (AD) have not been previously reported. In this study, we investigated the anti-dermatitis effect of FRA and its potential mechanism of action using a 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mouse model and lipopolysaccharide (LPS)-stimulated HaCaT cells. FRA significantly inhibited chronic pruritus, epidermal thickening, and inflammatory infiltration in AD mice. FRA not only inhibited the levels of IL-31 in the serum and lesioned skin of AD mice but also significantly downregulated the mRNA expression and protein levels of IL-31, IL-31RA, transient receptor potential (TRP) V1, and TRPA1 in the lesioned skin and dorsal root ganglion (DRG) of AD mice. In LPS-stimulated HaCaT cells, FRA inhibited the production of iNOS and COX2, as well as the protein levels of IL-31, IL-31RA, TRPV1 and TRPA1, showing significant anti-inflammatory effects. In summary, our findings suggest that FRA exerts antipruritic and anti-inflammatory effects in AD by regulating the IL-31 pathway, and may hold promise for the clinical treatment of AD.

Longitudinal variation of serum PCSK9 in ulcerative colitis: association with disease activity, T helper 1/2/17 cells, and clinical response of tumor necrosis factor inhibitor.

AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates CD4+ T cell differentiation and inflammatory response, the latter ones mediate ulcerative colitis (UC) initiation. This study intended to explore the correlation of serum PCSK9 with disease activity, T helper (h)1/Th2/Th17 cells, and clinical response of tumor necrosis factor inhibitor (TNFi) in UC patients. METHODS: In 65 UC patients underwent TNFi treatment, serum PCSK9 was evaluated at baseline (W0), week (W)2, W6, and W12 by enzyme-linked immunosorbent assays; meanwhile, Th1/Th2/Th17 cells were determined at W0 by flow cytometry. Besides, serum PCSK9 was detected in 65 healthy controls (HCs). RESULTS: Serum PCSK9 was increased in UC patients compared to HCs (P<0.001), which also positively correlated with C-reactive protein (P=0.009), total Mayo score (P=0.018), Mayo-defined disease activity (P=0.020), Th1 (P=0.033), and Th17 (P=0.003) cells, but not Th2 cells (P=0.086) in UC patients. Interestingly, serum PCSK9 was steadily declined from W0 to W12 (P<0.001). W2-W0, W6-W0, and W12-W0 serum PCSK9 change (PCSK9 at W2, W6, or W12 minus PCSK9 at W0, respectively) was gradually becoming greater during TNFi treatment (P<0.001). Furthermore, forty-five (69.2%) patients achieved clinical response at W12, whose serum PCSK9 at W6 (P=0.041) and W12 (P=0.001) was lower, and W6-W0 (P=0.043), W12-W0 (P=0.019) serum PCSK9 change was more obvious compared to patients without clinical response at W12. CONCLUSIONS: Serum PCSK9 is positively related to disease activity, Th1, and Th17 cells in UC patients; further, its decline correlates with TNFi response achievement in these patients.

Prophylactic nicotinamide mononucleotide (NMN) mitigates CSDS-induced depressive-like behaviors in mice via preserving of ATP level in the mPFC.

Depression is a prevalent psychiatric disorder with accumulating evidence implicating dysregulation of extracellular adenosine triphosphate (ATP) levels in the medial prefrontal cortex (mPFC). It remains unclear whether facilitating endogenous ATP production and subsequently increasing extracellular ATP level in the mPFC can exert a prophylactic effect against chronic social defeat stress (CSDS)-induced depressive-like behaviors and enhance stress resilience. Here, we found that nicotinamide mononucleotide (NMN) treatment effectively elevated nicotinamide adenine dinucleotide (NAD+) biosynthesis and extracellular ATP levels in the mPFC. Moreover, both the 2-week intraperitoneal (i.p.) injection and 3-week oral gavage of NMN prior to exposure to CSDS effectively prevented the development of depressive-like behavior in mice. These protective effects were accompanied with the preservation of both NAD+ biosynthesis and extracellular ATP level in the mPFC. Furthermore, catalyzing ATP hydrolysis by mPFC injection of the ATPase apyrase negated the prophylactic effects of NMN on CSDS-induced depressive-like behaviors. Prophylactic NMN treatment also prevented the reduction in GABAergic inhibition and the increase in excitability in mPFC neurons projecting to the lateral habenula (LHb). Collectively, these findings demonstrate that the prophylactic effects of NMN on depressive-like behaviors are mediated by preventing extracellular ATP loss in the mPFC, which highlights the potential of NMN supplementation as a novel approach for protecting and preventing stress-induced depression in susceptible individuals.

Network pharmacology-based analysis to explore the therapeutic mechanism of Cortex Dictamni on atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Dermatitis is a common clinical chronic inflammatory skin disease, which incidence has been on the rise in recent years. It not only seriously affects the physical and mental health of patients but also increase economic burden. Currently, commonly used drugs such as corticosteroids, anti-histamines have certain side effects or are expensive. Therefore, the search for an alternative therapy for dermatitis has important clinical significance. Cortex Dictamni is a commonly used traditional Chinese medicine for expelling wind and itching, but its mechanism for treating dermatitis is still unclear. MATERIALS AND METHODS: Network pharmacological analysis was performed to predict the potential targets and pathways of Cortex Dictamni against dermatitis. Molecular docking was used to assess the binding affinity of active compounds and core targets. By repeatedly stimulating the ears with 1-fluoro-2,4-dinitrobenzene (DNFB), an atopic dermatitis (AD) mouse model was established in order to study the anti-dermatitis effect of Cortex Dictamni. The skin thickness and inflammatory cell infiltration in mouse ears were assessed by tissue staining and flow cytometric. The levels of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), and the total protein and phosphorylation levels of related pathways were analyzed by western blotting. RESULTS: In this study, 11 active ingredients, 122 Cortex Dictamni and dermatitis intersection targets were identified. The results from Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the core targets were mainly enriched in immune response and inflammatory signaling pathways. AD mice treated with ethanol extract of Cortex Dictamni (ECD) improved the symptoms of ear skin lesions, alleviated epidermis and dermis thickening of the AD mice ears, decreased pathological immune cell infiltration and attenuated the levels of inflammatory cytokines (TLR4, IL-6, IL-17), and inhibited the hyperactivation of the PI3K-AKT, JAK1-STAT3/STAT6 signal pathways. CONCLUSIONS: Cortex Dictamni can improve the symptoms of skin lesions and the degree of inflammation caused by AD, and may inhibit AD through multiple pathways, such as regulating PI3K-AKT and JAK1-STAT3/STAT6 pathways. These results not only provide experimental evidence for the clinical application of Cortex Dictamni but also provide some help for the research and development of dermatitis drugs.

A Mouse Ear Model for Allergic Contact Dermatitis Evaluation.

Skin is the human body's first line of defense and one of the most exposed organs to environmental chemicals. Allergic contact dermatitis (ACD) is a common skin disease that manifests as a local rash, redness, and skin lesions. The occurrence and development of ACD are influenced by both genetic and environmental factors. Although many scholars have constructed a series of models of ACD in recent years, the experimental protocols of these models are all different, which makes it difficult for readers to establish them well. Therefore, a stable and efficient animal model is of great significance to further study the pathogenesis of atopic dermatitis. In this study, we detail a modeling method using 1-fluoro-2,4-dinitrobenzene (DNFB) to induce ACD-like symptoms in the ears of mice and describe several methods for assessing the severity of dermatitis during modeling. This experimental protocol has been successfully applied in some experiments and has a certain promotional role in the field of ACD research.

Multiple surgical treatment comparisons for irreparable rotator cuff tears: A network meta-analysis.

BACKGROUND: To evaluate the effect of different surgical methods in the treatment of patients with irreparable rotator cuff tears (IRCTs) using a network meta-analysis. METHODS: A search of the PubMed, EMbase, The Cochrane Library, VIP, WanFang Data, and CNKI databases was performed in January 2023 to search for randomized controlled trials and cohort studies of different surgical methods in the treatment of IRCTs. Risk assessment of the included randomized controlled trials was conducted using the risk of bias assessment tool recommended by the Cochrane Manual, and the Newcastle-Ottawa Scale was used for the risk assessment of cohort studies. Data were analyzed and plotted using Stata 15.0 software. RESULTS: A total of 17 studies involving 2123 patients and 10 surgical methods were included in this study. According to the surface under the cumulative ranking curve, the probability ranking in descending order is latissimus dorsi transfer (LDT) + partial repair > LDT > reverse total shoulder arthroplasty > superior capsular reconstruction > patch > partial repair > debridement + tenotomy of the long head of the biceps > debridement > in space subacromial balloon spacer + tenotomy of the long head of the biceps > in space subacromial balloon spacer. CONCLUSION: Among the multiple surgical treatments for patients with IRCTs, LDT + partial repair may have the best effect, and more randomized controlled trials with larger sample sizes are needed for further verification.

Dictamnine ameliorates chronic itch in DNFB-induced atopic dermatitis mice via inhibiting MrgprA3.

Chronic itch is the most prominent feature of atopic dermatitis (AD), and antihistamine treatment is often less effective in reducing clinical pruritus severity in AD. Multiple studies have shown that histamine-independent itch pathway is thought to predominate in AD-induced chronic itch. Mas-related G-protein-coupled receptor (Mrgpr) A3+ sensory neurons have been identified as one of the major itch-sensing neuron populations, and transient receptor potential (TRP) channel A1 is the key downstream of MrgprA3-mediated histamine-independent itch. MrgprA3-TRPA1 signal pathway is necessary for the development of chronic itch and may be the potentially promising target of chronic itch in AD. Dictamnine is one of the main quinoline alkaloid components of Cortex Dictamni (a traditional Chinese medicine widely used in clinical treatment of skin diseases). However, the anti-inflammatory and anti-pruritic effect of dictamnine on AD have not been reported. In this study, we used the 2,4-dinitrofluorobenzene (DNFB)-induced AD mouse model to observe the scratching behavior, inflammatory manifestations, and to detect the expression of MrgprA3 and TRPA1 in skin and DRG. The data demonstrated that dictamnine effectively inhibited AD-induced chronic itch, inflammation symptoms, epidermal thickening, inflammatory cell infiltration, and downregulated the expression of MrgprA3 and TRPA1. Furthermore, dictamnine restrained the excitability of MrgprA3+ and TRPA1+ neurons. Molecular docking also indicated that dictamnine has better binding affinity with MrgprA3. These results suggest that dictamnine may inhibit chronic itch caused by AD through the MrgprA3-TRPA1 mediated histamine-independent itch pathway, and may have a potential utility in AD treatment.

Multiplex signal amplification strategy-based early-stage diagnosis of Parkinson's disease on a SERS-enabled LoC system.

In this paper, a multiplex signal amplification strategy was developed for the determination of miR-214 and miR-221 on a surface-enhanced Raman scattering (SERS)-enabled lab-on-a-chip (LoC) system to realize the early-stage diagnosis of Parkinson's disease (PD). The gold nanobipyramids (GNBPs) with great monodispersity were functionalized with Raman reporter molecules and hairpin DNA 1, serving as the SERS nanotags. The presence of targets can initial the strand displacement amplification (SDA) reaction and the numerous short-stranded trigger DNA (tDNA) can be released under the action of polymerase and nicking enzyme. Then, the tDNA can trigger the catalytic hairpin assembly (CHA) event between the SERS nanotags and the capture nanoprobes (Magnetic beads (MBs) modified with hairpin DNA 2), resulting in the aggregation of GNBPs on the MBs surface. The multiplex signal amplification contributed by the SDA-CHA strategy and the magnet-induced aggregation effect can ultimately lead to the significant improvement of the detection sensitivity and the limit of detection (LOD) was low to aM level with reproducibility and specificity meanwhile. Furthermore, a MPTP-induced PD mice model was established to verify the practicability and the expression level of miR-214 and miR-221 at different stages analyzed with the LoC system was confirmed by qRT-PCR.

Combined SERS Microfluidic Chip with Gold Nanocone Array for Effective Early Lung Cancer Prognosis in Mice Model.

Introduction: As the most common malignant tumor in the world, the prognosis of patients with advanced lung cancer remains poor even after treatment. There are many prognostic marker assays available, but there is still more room for the development of high-throughput and sensitive detection of circulating tumor DNA (ctDNA). Surface-enhanced Raman spectroscopy (SERS), a spectroscopic detection method that has received wide attention in recent years, can achieve exponential amplification of Raman signals by using different metallic nanomaterials. Integrating SERS with signal amplification strategy into the microfluidic chip and applying it to ctDNA detection is expected to be an effective tool for the prognosis of lung cancer treatment effect in the future. Methods: To construct a high-throughput SERS microfluidic chip integrated with enzyme-assisted signal amplification (EASA) and catalytic hairpin self-assembly (CHA) signal amplification strategies, using hpDNA-functionalized Au nanocone arrays (AuNCAs) as capture substrates and cisplatin-treated lung cancer mice to simulate the detection environment for sensitive detection of ctDNA in serum of lung cancer patients after treatment. Results: The SERS microfluidic chip constructed by this scheme, with two reaction zones, can simultaneously and sensitively detect the concentrations of four prognostic ctDNAs in the serum of three lung cancer patients with a limit of detection (LOD) as low as the aM level. The results of the ELISA assay are consistent with this scheme, and its accuracy is guaranteed. Conclusion: This high-throughput SERS microfluidic chip has high sensitivity and specificity in the detection of ctDNA. This could be a potential tool for prognostic assessment of lung cancer treatment efficacy in future clinical applications.

Feruloylated oligosaccharides ameliorate MPTP-induced neurotoxicity in mice by activating ERK/CREB/BDNF/TrkB signalling pathway.

BACKGROUND: Feruloylated oligosaccharides (FOs) are natural esterification products of ferulic acid and oligosaccharides. STUDY DESIGN: In this study, we examined whether FOs contribute to the ensured survival of nigrostriatal dopamine neurons and inhibition of neuroinflammation in Parkinson's disease (PD). METHODS: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg) was injected intraperitoneally into mice to establish a Parkinson's disease (PD) mouse model. FOs (15 and 30 mg/kg) were orally administered daily to the MPTP-treated mice. The rotarod test, balance beam test, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), quantitative PCR (qPCR), and western blot analyses were performed to examine the neuroprotective effects of FOs on MPTP-treated mice. RESULTS: Our study indicated that FOs increased the survival of dopamine neurons in the substantia nigra pars compacta (SNc) of the MPTP-treated mice. The neuroprotective effects of FOs were accompanied by inhibited glial activation and reduced inflammatory cytokine production. The mechanistic experiments revealed that the neuroprotective effects of FOs might be mediated through the activation of the ERK/CREB/BDNF/TrkB signalling pathway. CONCLUSION: This study provides new insights into the mechanism underlying the anti-neuroinflammatory effect of phytochemicals and may facilitate the development of dietary supplements for PD patients. Our results indicate that FOs can be used as potential modulators for the prevention and treatment of PD.

"Jing-Ning Granules" Can Alleviate Attention Deficit Hyperactivity Disorder in Rats by Modulating Dopaminergic D2/D1-Like Receptor-Mediated Signaling Pathways.

Background: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by attention deficit, hyperactivity, and impulsivity. Jing-Ning Granules (JNG) is a traditional Chinese medicine (TCM) that can alleviate ADHD. Although JNG is commonly used for the effective treatment of ADHD and has obtained the national invention patent, the exact mechanism of action remains unclear. Objective: In this study, we examined the effect and mechanism of JNG in spontaneously hypertensive rats (SHRs). We hypothesized that JNG affects dopaminergic D2/D1-like receptors and related pathways. Materials and Methods: Six rat groups were used in the experiment: Wistar-Kyoto rats (WKY, control group) and five SHR groups, including a model group; atomoxetine (ATX, positive control) group; and low, medium, and high-dose JNG groups. The corresponding treatments were daily administered to each group for 6 weeks. A behavioral test, including a step-down test and open field test (OFT), was carried out at the end of treatment. After the behavioral test, all animals were sacrificed, and the brain tissue was collected and analyzed ex vivo; histopathological analysis was performed to assess the pathological changes of the hippocampus; expression of D1-like and D2-like receptors, sensor protein calmodulin (CaM), protein kinase A (PKA), and calcium/calmodulin-dependent serine/threonine protein kinase (CaMKII) in the striatum and hippocampus was measured by western blot and real-time quantitative PCR (RT-PCR); cyclic adenosine monophosphate (cAMP) levels in the striatum were analyzed using an enzyme-linked immunosorbent assay (ELISA), while the level of Ca2+ in the striatum was analyzed by a calcium kit. Results: Our results showed that ATX or JNG could ameliorate the hyperactive/impulsive behavior and cognitive function of ADHD by promoting neuroprotection. Mechanistically, ATX or JNG could prompt the expressions of Dl-like and D2-like receptors and improve the mRNA and protein levels of cAMP/PKA and Ca2+/CAM/CAMKII signaling pathways. Conclusion: These results indicate that JNG can produce therapeutic effects by regulating the balance of D2/D1-like receptor-mediated cAMP/PKA and Ca2+/CaM/CaMKII signaling pathways.

Characteristics of fine particulate matter (PM2.5) at Jinsha Site Museum, Chengdu, China.

Air pollution is a serious threat to ancient sites and cultural relicts. In this study, we collected indoor and outdoor PM2.5 samples and individual particles at the Exhibition Hall of Jinsha Site Museum in June 2020, and then the chemical components, sources, morphology, and mixing state of the fine particulate matter were analyzed. Our results show that the indoor and outdoor PM2.5 concentrations at the Exhibition Hall were 33.3±6.6 and 39.4±11.4 µg m-3, respectively. Although the indoor and outdoor concentrations of OC and EC were close, the proportion of secondary organic carbon in OC outdoor (33%) was higher than that indoor (27%). The PM2.5 was alkaline both indoors and outdoors, and the outdoor alkalinity was stronger than the indoor alkalinity. SNA (SO42-, NO3-, and NH4+) was the dominant component in the water-soluble inorganic ions; Na+, Mg2+, and Ca2+ were well correlated (R2> 0.9), and Cl- and K+ were also highly correlated (R2> 0.8). Enrichment factor analysis showed that Cu (indoor) and Cd were the main anthropogenic elements and that Cd was heavily enriched. Principal components analysis showed that the main sources of PM2.5 at Jinsha Site Museum were motor vehicles, dust, secondary sources, and combustion sources. The individual particles were classified as organic matter, S-rich, soot, mineral, and fly ash/metal particles, and most of these particles were internally mixed with each other. At last, we proposed pollution control measures to improve the air quality of museums and the preservation of cultural relicts.

Construction and Validation of Two Novel Nomograms for Predicting the Overall Survival and Cancer-Specific Survival of NSCLC Patients with Bone Metastasis.

BACKGROUND: Bone metastasis (BM) is the most common site of metastasis in non-small cell lung carcinoma (NSCLC). We aimed to construct and validate 2 novel nomograms predicting the 3-, 6-, and 12-months overall survival (OS) and cancer-specific survival (CSS). METHODS: The clinical data of 7480 patients between 2010 and 2016 were enrolled from the Surveillance, Epidemiology, and End Results database (SEER). The patients were allocated randomly to training and validation cohorts in a 7:3 ratio. Cox proportional hazards regression models were used to identify prognostic risk factors and establish 2 nomograms. The prediction accuracy of nomograms was assessed by C-index, the area under the ROC curve (AUC), and calibration curves. RESULTS: A total of 244998 NSCLC patients were identified between 2010 and 2016, with 7480 found with BM, accounting for 3.1%. Overall, 7480 patients were enrolled in the OS nomogram construction and were randomized to the training set (n = 5236) and the validation set (n = 2244). Age, sex, race, marital status, histology, grade, primary site, T stage, N stage, liver metastasis, surgery, radiotherapy, and chemotherapy were found to correlate with OS. A total of 7422 samples were included in the CSS nomogram construction, randomly grouped into training set (n = 5195) and the validation set (n = 2227). Age, sex, race, histology, grade, primary site, T stage, N stage, brain metastasis, liver metastasis, surgery, radiotherapy, and chemotherapy were associated with CSS. Two nomograms were conducted to predict the 3-, 6-, and 12-months OS and CSS. The ROC curves and exhibited good performance for predicting OS and CSS. CONCLUSION: We established and validated 2 high-performance nomograms to assist clinical doctors in making personalized treatment decisions.

Can probiotic supplements improve the symptoms of autism spectrum disorder in children?: A protocol for systematic review and meta analysis.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with increasing incidence. The externalizing and internalizing problems among children with ASD often persistent and highly impair functioning of both the child and the family. Children with ASD often develop gut-related comorbidities and dysbiosis can have negative effects on not only the gastrointestinal (GI) tract, but also psychological symptoms. Dietary exclusions and probiotic supplements also have been investigated in the management of ASD symptoms. Especially, there is some anecdotal evidence that probiotics supplements are able to alleviate GI symptoms as well as improve behaviors in children with ASD. METHOD AND ANALYSIS: This review will report on overall studies that include randomized control trials, randomized cross-over studies and cluster-randomized trials designs that consider curative effect in children with ASD by probiotic supplements. We will search 6 databases: MEDLINE, Embase, Scopus, PubMed, The Cochrane Library, and Web of Science and we will perform a manual search the journal Autism and information of ongoing or unpublished studies. The Mixed Methods Appraisal Tool (MMAT) will be used to assess quality of articles and the Jadad scale will be used to assess for bias. Assessment of publication bias will be performed using funnel plots generated by Comprehensive Meta-Analysis (CMA) 3.0 software. Clarifying the evidence in this area will be important for future research directions when reformulating and promoting the therapeutic regime in the field. ETHICS AND DISSEMINATION: There are no human participants, data, or tissue being directly studied for the purposes of the review; therefore, ethics approval and consent to participate are not applicable. The results of this study will be presented at conferences and published in peer-reviewed journals. REGISTRATION AND STATUS: PROSPERO 2019 CRD42019132754.

NRG1 accelerates the forgetting of fear memories and facilitates the induction of long-term depression in adult mice.

RATIONALE: Forgetting of fear memory is a current medical therapy for posttraumatic stress disorder (PTSD), and hippocampal long-term depression (LTD) may be the underlying mechanism. Neuregulin 1 (NRG1), a trophic factor, reportedly modulates memory consolidation and synaptic plasticity. METHODS: Fear memory was assessed using contextual fear conditioning. Electrophysiology was used to measure LTD and GABAergic transmission in the hippocampus. OBJECTIVES: To determine the contribution of hippocampal NRG1 to fear memory forgetting and low-frequency stimulation (LFS)-induced LTD. RESULTS: Administration of NRG1 in the hippocampus accelerated forgetting of contextual fear memories. Furthermore, NRG1 had no effect on low-frequency stimulation-induced LTD in young mice but significantly facilitated the induction of LTD and GABAergic transmission in adult animals. More importantly, NRG1-facilitated LTD induction in adult mice could be blocked by inhibition of GABAA receptors and NMDAR activation. CONCLUSION: These findings suggest a role for NRG1 in fear memory forgetting and hippocampal LTD, providing a potential target for the development of drug-assisted PTSD therapy.

Use of a Virtual Reality Simulator for Tendon Repair Training: Randomized Controlled Trial.

BACKGROUND: Virtual reality (VR) simulators have become widespread tools for training medical students and residents in medical schools. Students using VR simulators are provided with a 3D human model to observe the details by using multiple senses and they can participate in an environment that is similar to reality. OBJECTIVE: The aim of this study was to promote a new approach consisting of a shared and independent study platform for medical orthopedic students, to compare traditional tendon repair training with VR simulation of tendon repair, and to evaluate future applications of VR simulation in the academic medical field. METHODS: In this study, 121 participants were randomly allocated to VR or control groups. The participants in the VR group studied the tendon repair technique via the VR simulator, while the control group followed traditional tendon repair teaching methods. The final assessment for the medical students involved performing tendon repair with the "Kessler tendon repair with 2 interrupted tendon repair knots" (KS) method and the "Bunnell tendon repair with figure 8 tendon repair" (BS) method on a synthetic model. The operative performance was evaluated using the global rating scale. RESULTS: Of the 121 participants, 117 participants finished the assessment and 4 participants were lost to follow-up. The overall performance (a total score of 35) of the VR group using the KS method and the BS method was significantly higher (P<.001) than that of the control group. Thus, participants who received VR simulator training had a significantly higher score on the global rating scale than those who received traditional tendon repair training (P<.001). CONCLUSIONS: Our study shows that compared with the traditional tendon repair method, the VR simulator for learning tendon suturing resulted in a significant improvement of the medical students in the time in motion, flow of operation, and knowledge of the procedure. Therefore, VR simulator development in the future would most likely be beneficial for medical education and clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046648; http://www.chictr.org.cn/hvshowproject.aspx?id=90180.

Comparison of clinical and radiological outcomes of full-endoscopic versus microscopic lumbar decompression laminectomy for the treatment of lumbar spinal stenosis: a systematic review and meta-analysis.

BACKGROUND: To determine the clinical and radiological outcomes of full-endoscopic (FE) versus microscopic (MI) lumbar decompression laminectomy in the treatment of lumbar spinal stenosis (LSS), we performed a meta-analysis to explore the best choice for patients with LSS requiring surgical relief. METHODS: Literature searches of the PubMed, the Cochrane Library, Embase, Medline, Embase, and Web of Science databases were performed. The searches covered all indexed studies published between 2008 and 2020, using keywords identifying the patient group (lumbar spine stenosis) and the interventions (full-endoscopic lumbar decompression laminectomy and microscopic lumbar decompression laminectomy). A total of 1,727 patients were included in 10 studies. The primary outcomes of the analysis were visual analogue scale (VAS) scores for leg and back pain, and Oswestry Disability Index (ODI) score. RESULTS: The meta-analysis of the VAS score for low back pain showed that in the first 24 hours postoperatively, participants who underwent FE had better pain control than those who underwent MI [FE: mean difference (MD) =-0.78, 95% confidence interval (CI): -1.11, -0.45; MI: MD =-1.53, 95% CI: -1.94, -1.12]. In all subgroup analyses, the VAS score for back pain was lower in the FE group than in the MI group (MD =-0.71, 95% CI: -0.96, -0.47). Regarding the VAS score for leg pain, the FE group had a significantly lower score than the MI group in the first 24 hours (Total: MD =-1.02, 95% CI: -1.31, -0.73). The meta-analysis demonstrated that the FE group had a significantly lower ODI score than the MI group (MD =-1.03, 9% CI: -1.54, -0.51). At 6 months, the MI group had a significantly lower score than the FE group (MD =1.09, 95% CI: 0.53, 1.64), but at 12 months, the FE group had a significantly lower score than the MI group (MD =-2.40, 95% CI: -3.12, -1.67). DISCUSSION: Compared to MI decompression, the FE decompression method resulted in better pain control in the early postoperative period, both in the lower back and legs, as well as shorter operative and shorter hospitalization times.