Echinococcus multilocularis serpin regulates macrophage polarization and reduces gut dysbiosis in colitis.

Helminths serve as principal regulators in modulating host immune responses, and their excretory-secretory proteins are recognized as potential therapeutic agents for inflammatory bowel disease. Nevertheless, our comprehension of the mechanisms underlying immunoregulation remains restricted. This investigation delves into the immunomodulatory role of a secretory protein serpin (Emu-serpin), within the larval stage of Echinococcus multilocularis. Our observations indicate that Emu-serpin effectively alleviates dextran sulfate sodium-induced colitis, yielding a substantial reduction in immunopathology and an augmentation of anti-inflammatory cytokines. Furthermore, this suppressive regulatory effect is concomitant with the reduction of gut microbiota dysbiosis linked to colitis, as evidenced by a marked impediment to the expansion of the pathobiont taxa Enterobacteriaceae. In vivo experiments demonstrate that Emu-serpin facilitates the expansion of M2 phenotype macrophages while concurrently diminishing M1 phenotype macrophages, alongside an elevation in anti-inflammatory cytokine levels. Subsequent in vitro investigations involving RAW264.7 and bone marrow macrophages reveal that Emu-serpin induces a conversion of M2 macrophage populations from a pro-inflammatory to an anti-inflammatory phenotype through direct inhibition. Adoptive transfer experiments reveal the peritoneal macrophages induced by Emu-serpin alleviate colitis and gut microbiota dysbiosis. In summary, these findings propose that Emu-serpin holds the potential to regulate macrophage polarization and maintain gut microbiota homeostasis in colitis, establishing it as a promising candidate for developing helminth therapy for preventing inflammatory diseases.

MAFLD with central obesity is associated with increased risk of colorectal adenoma and high-risk adenoma.

OBJECTIVE: To analyze the risk factors associated with colorectal adenoma and to investigate the associations of metabolism-related fatty liver disease (MAFLD) with obesity, colorectal adenoma and high-risk adenoma. METHODS: A total of 1395 subjects were enrolled and divided into a colorectal adenoma group (593 subjects) and a control group (802 subjects) according to the inclusion and exclusion criteria. The characteristics of patients in the colorectal adenoma group and the control group were compared by the chi-square test. Univariate and multivariate logistic analyses were used to analyze independent risk factors and associations with different MAFLD subtypes. Colorectal adenoma characteristics and the proportion of patients with high-risk colorectal adenoma were also compared. RESULTS: High-density lipoprotein (HDL-C) was significantly lower in patients in the colorectal adenoma group than in those in the control group (P < 0.001). Logistic regression analysis revealed that age, obesity status, central obesity status, hypertension status, diabetes status, fatty liver status, smoking history, BMI, waist circumference, triglyceride level, HDL-C level, fasting blood glucose level and degree of hepatic steatosis were all independent risk factors for colorectal adenoma. Notably, MAFLD was associated with a significantly increased risk of colorectal adenoma in patients with central obesity (P < 0.001). In addition, obesity, central obesity, diabetes, fatty liver and degree of hepatic steatosis were all shown to be independent risk factors for high-risk colorectal adenoma. In addition, a greater proportion of MAFLD patients with central obesity than those without central obesity had high-risk colorectal adenoma. CONCLUSION: MAFLD and central obesity are independently associated with the development of colorectal adenoma. MAFLD with central obesity is associated with an increased risk of colorectal adenoma and high-risk adenoma.

A novel variant (p.A524P) in Spastin is responsible for a Chinese family with hereditary spastic paraplegia.

BACKGROUND: Hereditary spastic paraplegia (HSP) represents a group of monogenic neurodegenerative disorders characterized by high clinical and genetic heterogeneity. HSP is characterized by slowly progressing hypertonia of both lower extremities, spastic gait, and myasthenia. The most prevalent autosomal dominant form of HSP, known as spastic paraplegia 4 (SPG4), is attributed to variants in the spastin (SPAST) gene. METHODS AND RESULTS: Here, a Chinese family presenting with spasticity in both legs and a shuffling gait participated in our investigation. Whole exome sequencing of the proband was utilized to identify the genetic lesion in the family. Through data filtering, Sanger sequencing validation, and co-separation analysis, a novel variant (NM_014946.3: c.1669G > C:p.A557P) of SPAST was identified as the genetic lesion of this family. Furthermore, bioinformatic analysis revealed that this variant was deleterious and located in a highly evolutionarily conserved site. CONCLUSION: Our study confirmed the diagnosis of SPG4 in this family, contributing to genetic counseling for families affected by SPG4. Additionally, our study broadened the spectrum of SPAST variants and highlighted the importance of ATPases associated with various cellular activity domains of SPAST.

Overall signature of acquired KRAS gene changes in advanced non-small cell lung cancer patient with EGFR-TKI resistance.

OBJECTIVE: Numerous scattered case studies continue to demonstrate a strong correlation between acquired KRAS mutations and epidermal growth factor receptor-tyrosine kinase inhibitor resistance in non-small cell lung cancer. However, the comprehensive understanding of the KRAS pathway following the failure of epidermal growth factor receptor-tyrosine kinase inhibitor therapy remains limited. METHODS: We conducted a retrospective evaluation of the next generation sequencing data from 323 patients with advanced non-small cell lung cancer and EGFR-activating mutations after experiencing progression with epidermal growth factor receptor-tyrosine kinase inhibitor therapy. Our analysis specifically focused on the acquired changes to the KRAS gene. RESULTS: Among the 323 patients with advanced non-small cell lung cancer and EGFR-activating mutations who experienced resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy, 14 individuals (4.3%) developed resistance due to acquired KRAS alterations. Of these 14 patients, 10 cases (71.4%) were due to KRAS missense mutations, 1 case (7.2%) was due to KRAS gene fusion and 3 cases (21.4%) were due to KRAS amplification. Notably, we identified one newly demonstrated KRAS gene fusion (KRAS and LMNTD1), one KRAS G13D and one KRAS K117N. The emergence of acquired KRAS alterations was often accompanied by novel mutations and high tumor mutation burden, with TP53, CNKN2A, PIK3CA, MYC, STK11, CDK4, BRCA2 and ERBB2 being the most frequently observed concurrent mutations. The median progression-free survival and overall survival for the 14 patients were 5.2 and 7.3 months, respectively. Acquired KRAS missense variants were associated with significantly worse progression-free survival compared with other KRAS variant subtypes (P < 0.028). CONCLUSIONS: This study provides significant evidence of the role of acquired KRAS variants in the development of resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy. Our results contribute to the growing body of knowledge on the mutational profiles associated with resistance to epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Furthermore, our study highlights the KRAS gene change as a significant mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy.

Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Cognitive impairment and depression precede increased HDL-C levels in middle-aged and older Chinese adults: cross-lagged panel analyses.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. METHODS: The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. RESULTS: The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (ß = - 0.036 and ß = 0.028, respectively, P < 0.05). However, higher baseline HDL-C levels did not significantly predict cognitive performance or depression 4 years later (ß = - 0.008 and ß = 0.023, respectively, P > 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (ß = - 0.026 and ß = - 0.053, respectively, P < 0.05). CONCLUSIONS: Cognitive impairment and depression are associated with higher HDL-C levels, whereas higher HDL-C levels do not appear to protect against cognitive decline or depressive symptoms. These findings underscore the importance of preserving cognitive and mental health, which may lower the likelihood of cardiovascular disease and dementia. Future studies should validate these findings and develop targeted interventions tailored to specific populations.

Severe food allergy reactions are associated with α-tryptase.

BACKGROUND: Increased TPSAB1 copy numbers encoding ⍺-tryptase are associated with severe reactions in adults with Hymenoptera venom allergy, systemic mastocytosis, and idiopathic anaphylaxis. OBJECTIVE: The primary objective was to assess the association between ⍺-tryptase and severity of food allergy. METHODS: A total of 119 subjects underwent tryptase genotyping; 82 of them were from an observational food allergy cohort at the National Institute of Allergy and Infectious Disease (NIAID), and 37 were from a cohort of children who reacted to peanut oral food challenge (OFC) at Lurie Children's Hospital of Chicago. The primary predictor was presence or absence of ⍺-tryptase. The primary outcomes for both cohorts were measures of severity of food allergy reaction. Secondary outcomes included OFC symptom scores (Bock/Practical Allergy [PRACTALL] and Severity Grading Score for Acute Reactions [SGSAR]). Correlation between total α-tryptase isoforms and OFC scores was also assessed to account for gene dosage effects. RESULTS: Among the subjects in the NIAID cohort, the presence of ⍺-tryptase was associated with a higher prevalence of food-triggered anaphylaxis than in those with only ß-tryptase (P = .026). Similarly, only 1 of 6 subjects in the OFC cohort with only ß-tryptase (17%) had a severe reaction, whereas 20 of 31 of subjects with α-tryptase (65%) had a severe reaction (P = .066). Subjects with ⍺-tryptase also had higher total SGSAR scores than did the subjects with no ⍺-tryptase (P = .003). In addition, there were also significant positive correlations between ⍺-tryptase isoform copy numbers and both higher total SGSAR and Bock/PRACTALL OFC scores (P = .008 and P = .003, respectively). CONCLUSION: The presence of α-tryptase in subjects is correlated with a higher prevalence of anaphylaxis or severe reaction to food than in subjects without any α-tryptase.

The Role of the Mu Opioid Receptors of the Medial Prefrontal Cortex in the Modulation of Analgesia Induced by Acute Restraint Stress in Male Mice.

Mu opioid receptors (MORs) represent a vital mechanism related to the modulation of stress-induced analgesia (SIA). Previous studies have reported on the gamma-aminobutyric acid (GABA)ergic "disinhibition" mechanisms of MORs on the descending pain modulatory pathway of SIA induced in the midbrain. However, the role of the MORs expressed in the medial prefrontal cortex (mPFC), one of the main cortical areas participating in pain modulation, in SIA remains completely unknown. In this study, we investigated the contributions of MORs expressed on glutamatergic (MORGlut) and GABAergic (MORGABA) neurons of the medial prefrontal cortex (mPFC), as well as the functional role and activity of neurons projecting from the mPFC to the periaqueductal gray (PAG) region, in male mice. We achieved this through a combination of hot-plate tests, c-fos staining, and 1 h acute restraint stress exposure tests. The results showed that our acute restraint stress protocol produced mPFC MOR-dependent SIA effects. In particular, MORGABA was found to play a major role in modulating the effects of SIA, whereas MORGlut seemed to be unconnected to the process. We also found that mPFC-PAG projections were efficiently activated and played key roles in the effects of SIA, and their activation was mediated by MORGABA to a large extent. These results indicated that the activation of mPFC MORGABA due to restraint stress was able to activate mPFC-PAG projections in a potential "disinhibition" pathway that produced analgesic effects. These findings provide a potential theoretical basis for pain treatment or drug screening targeting the mPFC.

Whole-exome sequencing detected a novel AIFM1 variant in a Han-Chinese family with Cowchock syndrome.

Charcot-Marie-Tooth disease(CMT) is a hereditary peripheral neuropathy, characterized by progressive distal hypoesthesia and amyotrophia. CMT is characterized by an X- linked recessive inheritance pattern. The apoptosis-inducing factor mitochondria associated-1 (AIFM1) is the main pathogenic gene of the X-linked recessive Charcot-Marie-Tooth disease-4 with or without cerebellar ataxia (CMTX4), also known as Cowchock syndrome. In this study, we enrolled a family with CMTX from the southeast region of China and identified a novel AIFM1 variant (NM_004208.3: c.931C>G; p.L311V) using whole exon sequencing technology. The results of our study may also be useful for genetic counseling, embryo screening of in vitro fertilization embryos, and prenatal genetic diagnosis.

The effects of palliative care on patients with different classes heart function: A pilot study.

The aim of this study was to explore effects of palliative care (PC) on patients with different heart function. Patients with NYHA (New York Heart Association) class II, III, IV were divided into separate groups. The KCCQ (Kansas City Cardiomyopathy Questionnaire) and HADS (Hospital Anxiety and Depression Scale) scores were compared before and 3 months after PC intervention. After 3 months, compared with the control group, PC could further significantly improve the KCCQ, HADS-depression and -anxiety scores of patients in NYHA class IV (P < 0.05); PC could significantly improve the HADS-depression and -anxiety scores of patients with NYHA class III (P < 0.05), and had an improvement tendency on KCCQ score. The study revealed that PC can significantly improve anxiety and depression of patients with NYHA class III or IV, and significantly improve the quality of life of patients with NYHA class IV, but had no effects on patients with NYHA class II.

Comparison of the learning curve of robot-assisted and laparoscopic-assisted gastrectomy. / æœºå™¨äººè¾ åŠ©ä¸Žè ¹è ”é•œè¾ åŠ©èƒƒåˆ‡é™¤æœ¯å­¦ä¹ æ›²çº¿çš„æ¯”è¾ƒ.

OBJECTIVES: Da Vinci robot technology is widely used in clinic,with minimally invasive surgery development. This study aims to explore the possible influence of advanced surgical robotics on the surgery learning curve by comparing the initial clinical learning curves of 2 different surgical techniques: robotic-assisted gastrectomy (RAG) and laparoscopic-assisted gastrectomy (LAG). METHODS: From September 2017 to December 2020, a chief surgeon completed a total of 108 cases of radical gastric cancer from the initial stage, including 27 cases of RAG of the Da Vinci Si robotic system (RAG group) and 81 cases of LAG (LAG group). The lymph node of gastric cancer implemented by the Japanese treatment guidelines of gastric cancer. The surgical results, postoperative complications, oncology results and learning curve were analyzed. RESULTS: There was no significant difference in general data, tumor size, pathological grade and clinical stage between the 2 groups (P>0.05). The incidence of serious complications in the RAG group was lower than the LAG group (P=0.003). The intraoperative blood loss in the RAG group was lower than that in the LAG group (P=0.046). The number of lymph nodes cleaned in the RAG group was more (P=0.003), among which there was obvious advantage in lymph node cleaning in the No.9 group (P=0.038) and 11p group (P=0.015). The operation time of the RAG group was significantly longer than the LAG group (P=0.015). The analysis of learning curve found that the cumulative sum analysis (CUSUM) value of the RAG group decreased from the 10th case, while the CUSUM of the LAG group decreased from the 28th case. The learning curve of the RAG group had fewer closing cases than that of the LAG group. The unique design of the surgical robot might help to improve the surgical efficiency and shorten the surgical learning curve. CONCLUSIONS: Advanced robotics helps experienced surgeons quickly learn to master RAG skills. With the help of robotics, RAG are superior to LAG in No.9 and 11p lymph node dissection and surgical trauma reduction. RAG can clear more lymph nodes than LAG, and has better perioperative effect.

Dynamic Hydrogen-Bond Network as a Modulator of Bismuth-Antimony Complex Anodes for Self-Healable and Wider Temperature Adaptive Potassium Ion Batteries.

Antimony (Sb)-based anodes are attractive candidates in potassium-ion batteries (PIBs) due to their superior capacities and rational potassium inserting voltages. However, the sluggish kinetics and poor interface compatibility severely hinder practical application. Herein, Bi0.67 Sb1.33 S3 nanospheres embedded into in situ formed poly(3,4-ethylenedioxythiophene) crosslinked with polythioctic acid (PET@PTA) (Bi0.67 Sb1.33 S3 /PET@PTA) were elaborately conceptualized with hydrogen bonds exchangeable binding (HBEB) sites. Bi0.67 Sb1.33 S3 /PET@PTA exhibits notable self-healing ability and wider temperature adaptability. Bi0.67 Sb1.33 S3 /PET@PTA displays an impressive capacity of 819 mAh g-1 at 0.05 A g-1 , prominent cycle ability with a 73 % capacity conservation after 500 cycles at 2 A g-1 , and high capacity retention of 66 % and 84 % at -40 and 70 °C to that case at room temperature, respectively, for potassium storage. This work provides a new perspective for HBEB sites in maximizing the desirable K+ storage performance.

Cryogenic mid-wave infrared hyperspectral Fabry-Perot filter based on a tensile-strained single-layer subwavelength grating mirror.

We report here the first demonstration of a cryogenic mid-wave infrared (MWIR) hyperspectral fixed-cavity Fabry-Perot filter based on a suspended tensile-strained single-layer 2-D subwavelength grating (SWG) mirror. Optical design optimization of the 2-D SWG mirror and parameter tolerance study are performed. For the first time, process control of grating air-hole sidewall angle and the grating air-hole fill-factor fabrication error caused by e-beam lithography electron-scattering effect is reported. At 80 K, namely the operating temperature of MWIR photodetectors, the as-fabricated suspended 2-D SWG mirror has achieved excellent surface flatness with a slight center-to-edge bowing of 15 nm over a 1-mm2 large mirror area and a high average reflectivity of 0.97 across a wavelength range of 3.72-5 µm, which represents an unprecedentedly wide fractional bandwidth Δλ/λc of 30%. The cryogenically cooled Fabry-Perot filter exhibits an unrivaled high spectral resolution of 10 nm that far exceeds the optical requirement for MWIR hyperspectral imaging applications.

Three Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer: Similarities and Differences.

Osimertinib, almonertinib and furmonertinib are third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) approved for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutation. This article reviews research advances in pharmacokinetics, pharmacodynamics, treatment-related adverse events, and other aspects related to the three EGFR-TKIs were systematically reviewed in order to provide references for clinical drug selection. There are differences in dosing schedule and incidence of adverse events among three drugs. Optimization of third-generation EGFR-TKIs options for individuals may produce the maximal benefits to NSCLC patients with EGFR T790M mutation.

Heritable risk for severe anaphylaxis associated with increased α-tryptase-encoding germline copy number at TPSAB1.

BACKGROUND: An elevated basal serum tryptase level is associated with severe systemic anaphylaxis, most notably caused by Hymenoptera envenomation. Although clonal mast cell disease is the culprit in some individuals, it does not fully explain this clinical association. OBJECTIVE: Our aim was to determine the prevalence and associated impact of tryptase genotypes on anaphylaxis in humans. METHODS: Cohorts with systemic mastocytosis (SM) and venom as well as idiopathic anaphylaxis from referral centers in Italy, Slovenia, and the United States, underwent tryptase genotyping by droplet digital PCR. Associated anaphylaxis severity (Mueller scale) was subsequently examined. Healthy volunteers and controls with nonatopic disease were recruited and tryptase was genotyped by droplet digital PCR and in silico analysis of genome sequence, respectively. The effects of pooled and recombinant human tryptases, protease activated receptor 2 agonist and antagonist peptides, and a tryptase-neutralizing mAb on human umbilical vein endothelial cell permeability were assayed using a Transwell system. RESULTS: Hereditary α-tryptasemia (HαT)-a genetic trait caused by increased α-tryptase-encoding Tryptase-α/ß1 (TPSAB1) copy number resulting in elevated BST level-was common in healthy individuals (5.6% [n = 7 of 125]) and controls with nonatopic disease (5.3% [n = 21 of 398]). HαT was associated with grade IV venom anaphylaxis (relative risk = 2.0; P < .05) and more prevalent in both idiopathic anaphylaxis (n = 8 of 47; [17%; P = .006]) and SM (n = 10 of 82 [12.2%; P = .03]) relative to the controls. Among patients with SM, concomitant HαT was associated with increased risk for systemic anaphylaxis (relative risk = 9.5; P = .007). In vitro, protease-activated receptor-2-dependent vascular permeability was induced by pooled mature tryptases but not α- or ß-tryptase homotetramers. CONCLUSIONS: Risk for severe anaphylaxis in humans is associated with inherited differences in α-tryptase-encoding copies at TPSAB1.

Routine KIT p.D816V screening identifies clonal mast cell disease in patients with Hymenoptera allergy regularly missed using baseline tryptase levels alone.

BACKGROUND: Clonal mast cell disorders and elevated basal serum tryptase (BST) levels with unknown cause(s) are associated with severe Hymenoptera venom-triggered anaphylaxis (HVA). However, some individuals with clonal disease have a normal BST level (<11.4 ng/mL). OBJECTIVE: Our aim was to evaluate whether screening for KIT p.D816V in the blood is a useful clinical tool to risk-stratify patients with venom allergy. METHODS: We prospectively recruited 374 patients with Hymenoptera allergy and no overt signs of mastocytosis who were referred to our center during the years 2018 and 2019. KIT p.D816V was determined in their peripheral blood by quantitative PCR, and tryptase genotyping was performed by droplet digital PCR. RESULTS: In all, 351 patients (93.9%) had normal levels of BST, and KIT p.D816V was detected in 8% of patients (28 of 351), predominantly in patients with the most severe Mueller grade IV anaphylaxis (18.2% [24 of 132] vs 1.8% in patients with lower grades [4 of 88 with grade III and 0 of 131 with other grades]; P < .001). In grade IV patients with a normal BST level, KIT p.D816V was associated with more severe symptoms, including a significantly higher frequency of loss of consciousness (58.3% [14 of 24] vs 34.3% [37 of 108]; P = .03) and absence of skin symptoms (41.7% [10 of 24] vs 15.7% [17 of 108]; P = .004). Among patients with a normal BST level, KIT p.D816V (OR = 10.25 [95% CI = 3.75-36.14]; P < .0001) was the major risk factor associated with severe HVA. Hereditary α-tryptasemia (HαT) due to increased germline copies of TPSAB1 encoding α-tryptase was the most common cause (65.2% [15 of 23]) of elevated BST level in patients with HVA, and together with KIT p.D816V, it accounted for 90% of BST level elevations (20 of 23) in patients with HVA. CONCLUSION: These results indicate that routine KIT p.D816V screening identifies clonal disease in high-risk patients with HVA who are regularly missed when BST level is used alone.

[Analysis of the Effects of Femoral Nerve Block on Pain Level and Knee Mobility in Patients With Total Knee Replacement].

BACKGROUND: Osteoarthritis is a common cause of inactivity and reduced quality of life in the elderly. Total knee replacement (TKR) surgery, a last-stage treatment option for osteoarthritis, often results in postoperative pain that influences knee flexion and the ability to perform prescribed rehabilitation exercises. PURPOSE: This study was designed to examine the effectiveness of single femoral nerve block (FNB) on pain level and knee mobility in patients with TKR. METHODS: A quasi-experimental, two-group, longitudinal study was designed. The participants were distributed into the FNB group (n = 86) and non-FNB group (n = 86). The outcome measurements included pain scale (Numerical Rating Scale) score and knee continuous passive motion knee flexion angle. The five assessments and followed-up times were as follows: admission day (T0) and post-surgery day 1, 2, 3, and 4. RESULTS: The results of the generalized estimating equations model showed that the pain level in the FNB group was significantly lower than in the non-FNB group, (p < .001). In terms of analgesics demand from post-surgery day 1 to day 4, the FNB group exhibited a significantly lower demand than the non-FNB group (p < .01). In addition, significant differences in the continuous passive motion rehabilitation exercise angle were found between the two groups from post-surgery day 1 through day 4 (p < .05). Finally, significant differences in knee flexion angles between the two groups were observed between hospital admission and discharge (p < .001). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The findings of this study support the positive effects of the femoral nerve block intervention on patients who receive total knee replacement surgery. The results were significant in terms of pain relief and knee mobility recovery. This intervention should be made available for use in the clinical care of TKR patients.

An auto real-time jump tagging system for exploring stereotyped jumping behavior in mice.

The jump is one of the common stereotyped behavior in rodents which can be found in certain types of disease models, such as addiction. It can be easily identified by the human eye. However, it is difficult to be tagged in real-time by manual operation, which limits the detailed exploration of its neural mechanisms with the new techniques, such as fiber photometry recording. Here we introduced an auto real-time jump tagging system (Art-JT system) to record the jump based on online monitoring the pressure changes of the floor in which the mouse is free exploring. Meanwhile, the Art-JT system can send the digital signal of the jump timing to the external device for tagging the events in the fiber photometry system. We tested it with the mice induced by Naloxone precipitated withdrawal jumping and found that it could accurately record the jump events and provide several detailed parameters of the jump. We also confirmed that the jump was correlated with the medial prefrontal cortex and primary motor cortex neuronal activities by combining the Art-JT system, GCaMP6 mice, and fiber photometry system. Our results suggested that the Art-JT system may be a powerful tool for recording and analyzing jumps efficiently and helping us to understand stereotyped behavior.

Transcriptome analysis reveals key genes and pathways associated with piglet fetal mummification.

China has the largest pork consumption worldwide. However, the high incidence of piglet fetal mummification (3%-5%) is an important factor that causes the slow improvement of pig reproductive capacity, and the genetic mechanism is still unclear. This study aimed to identify candidate genes associated with piglet fetal mummification. RNA-seq technology was used to compare transcriptome profiling of blood from healthy and mummified piglets at different stages of pregnancy (35, 56, 77, and 98 days). A total of 137-420 differentially expressed genes (DEGs) were detected at each stage. Seven DEGs were significantly differentially expressed at various stages. IL-9R, TLR8, ABLIM3, FSH-α, ASCC1, PRKCZ, and GCK may play important roles in the course of piglet fetal mummification. The differential genes we identified between the groups were mainly enriched in immune and inflammation regulation, while others were mainly enriched in reproduction. Considering the function of candidate genes, IL-9R and TLR8 were suggested as the most promising candidate genes involved in mummified piglet traits. We speculate that during pregnancy, it may be the combined effects of the above-mentioned inflammation, immune response, and reproduction-related signaling pathways that affect the occurrence of mummified piglets and further affect pig reproduction.

Establishment and validation of a prediction model for the probability of malignancy in solid solitary pulmonary nodules in northwest China.

BACKGROUND AND OBJECTIVES: To construct a prediction model of solitary pulmonary nodules (SPNs), to predict the possibility of malignant SPNs in patients aged 15-85 years in northwest China for clinical diagnostic and therapeutic decision-making. METHODS: The features of SPNs were assessed by multivariate logistic regression, followed by visualization using a nomogram. Hosmer lemeshow was applied to evaluate the fitting degree of the model. The area under the receiver operating characteristic (ROC) curve was identified to determine the discriminative ability of the model. RESULTS: Lobulation, spiculation, pleural-tag, carcinoembryonic antigen, neuron-specific enolase, and total serum protein were independent predictors of malignant pulmonary nodules (p < .05). Lobulation (100 points) scored the highest in the nomogram, and the Hosmer-Lemeshow goodness-of-fit statistic was 0.805 (p > .05). The area under curve (AUC) of the modeling and validation groups using logistic regression were 0.859 (95% CI, 0.805-0.903) and 0.823 (95% CI, 0.738-0.890), respectively. Moreover, the AUC of our model was higher than that of the Mayo model, VA model, and Peking University (AUC 0.823 vs. 0.655 vs. 0.603 vs. 0.521). CONCLUSION: Our prediction model is more suitable for predicting the possibility of malignant SPNs in northwest China, and can be calculated using a nomogram to determine further treatments.