PcEiger links the Imd/Relish pathway to ROS production in the intestine of the red swamp crayfish.

In the arthropod gut, commensal microbiota maintain the immune deficiency (Imd)/Relish pathway for expression of antimicrobial peptides, whereas pathogenic bacteria induce dual oxidase 2 (Duox2) for production of extracellular microbicidal reactive oxygen species (ROS). The Imd/Relish pathway and the Duox2/ROS system are regarded as independent systems. Here, we report that these two systems are bridged by the tumor necrosis factor (TNF) ortholog PcEiger in the red swamp crayfish Procambarus clarkii. PcEiger expression is induced by commensal bacteria or the Imd/Relish pathway. PcEiger knockdown alters bacterial abundance and community composition due to variations in the oxidative status of the intestine. PcEiger induces Duox2 expression and ROS production by regulating the activity of the transcription factor Atf2. Moreover, PcEiger mediates regulation of the Duox2/ROS system by commensal bacteria and the Imd/Relish pathway. Our findings suggest that the Imd/Relish pathway regulates the Duox2/ROS system via PcEiger in P. clarkii, and they provide insights into the crosstalk between these two important mechanisms for arthropod intestinal immunity.

Genome-wide analysis and expression profiling of the HD-ZIP gene family in kiwifruit.

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.

AntDAS-GCMS: A New Comprehensive Data Analysis Platform for GC-MS-Based Untargeted Metabolomics with the Advantage of Addressing the Time Shift Problem.

Over the years, a number of state-of-the-art data analysis tools have been developed to provide a comprehensive analysis of data collected from gas chromatography-mass spectrometry (GC-MS). Unfortunately, the time shift problem remains unsolved in these tools. Here, we developed a novel comprehensive data analysis strategy for GC-MS-based untargeted metabolomics (AntDAS-GCMS) to perform total ion chromatogram peak detection, peak resolution, time shift correction, component registration, statistical analysis, and compound identification. Time shift correction was specifically optimized in this work. The information on mass spectra and elution profiles of compounds was used to search for inherent landmarks within analyzed samples to resolve the time shift problem across samples efficiently and accurately. The performance of our AntDAS-GCMS was comprehensively investigated by using four complex GC-MS data sets with various types of time shift problems. Meanwhile, AntDAS-GCMS was compared with advanced GC-MS data analysis tools and classic time shift correction methods. Results indicated that AntDAS-GCMS could achieve the best performance compared to the other methods.

Small immune effectors coordinate peptidoglycan-derived immunity to regulate intestinal bacteria in shrimp.

Small antibacterial effectors, including lysozymes, lectins, and antimicrobial peptides, are key regulators of intestinal immunity. However, whether there is coordination among them during regulation is an interesting, but largely unknown, issue. In the present study, we revealed that small effectors synergistically regulate peptidoglycan-derived intestinal immunity in the kuruma shrimp, Marsupenaeus japonicus. A C-type lysozyme (LysC) was screened as a responsive factor for the intestine-bacteria interaction. LysC functions to restrict intestinal bacteria, mainly by cleaving Photobacterium damselae peptidoglycan to generate muropeptides which are powerful stimulators that induce anti-lipopolysaccharides factor B1 (AlfB1), an effective bactericidal peptide. The muropeptides also induce a C-type lectin (Ctl24), which recognizes peptidoglycan and coats bacteria. By counteracting LysC-mediated muropeptide release and AlfB1's bactericidal activity, Ctl24 prevents the continuous elimination of intestinal bacteria. Therefore, this study demonstrates a mechanism by which small immune effectors coordinate to achieve intestinal homeostasis, and provides new insights into peptidoglycan-derived intestinal immunity in invertebrates.

Red blood cell distribution width is associated with sarcopenia risk in early-stage non-small cell lung cancer.

BACKGROUND: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. METHODS: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. RESULTS: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. CONCLUSION: RDW is associated with sarcopenia risk in early-stage NSCLC.

Growth and thermal maturation of the Toba magma reservoir.

The Toba volcanic system in Indonesia has produced two of the largest eruptions (>2,000 km3 dense-rock equivalent [DRE] each) on Earth since the Quaternary. U-Pb crystallization ages of zircon span a period of ∼600 ky before each eruptive event, and in the run-up to each eruption, the mean and variance of the zircons' U content decrease. To quantify the process of accumulation of eruptible magma underneath the Toba caldera, we integrated these observations with thermal and geochemical modeling. We show that caldera-forming eruptions at Toba are the result of progressive thermal maturation of the upper crustal magma reservoir, which grows and chemically homogenizes, by sustained magma influx at average volumetric rates between 0.008 and 0.01 km3/y over the past 2.2 My. Protracted thermal pulses related to magma-recharge events prime the system for eruption without necessarily requiring an increased magma-recharge rate before the two supereruptions. If the rate of magma input was maintained since the last supereruption of Toba at 75 ka, eruptible magma is currently accumulating at a minimum rate of ∼4.2 km3 per millennium, and the current estimate of the total volume of potentially eruptible magma available today is a minimum of ∼315 km3 Our approach to evaluate magma flux and the rate of eruptible magma accumulation is applicable to other volcanic systems capable of producing supereruptions and thereby could help in assessing the potential of active volcanic systems to feed supereruptions.

Dual Synthetic Receptor-Based Sandwich Electrochemical Sensor for Highly Selective and Ultrasensitive Detection of Pathogenic Bacteria at the Single-Cell Level.

Sensitive and rapid detection of pathogenic bacteria is essential for effective source control and prevention of microbial infectious diseases. However, it remains a substantial challenge to rapidly detect bacteria at the single-cell level. Herein, we present an electrochemical sandwich sensor for highly selective and ultrasensitive detection of a single bacterial cell based on dual recognition by the bacteria-imprinted polymer film (BIF) and aptamer. The BIF was used as the capture probe, which was in situ fabricated on the electrode surface within 15 min via electropolymerization. The aptamer and electroactive 6-(Ferrocenyl)hexanethiol cofunctionalized gold nanoparticles (Au@Fc-Apt) were employed as the signal probe. Once the target bacteria were anchored on the BIF-modified electrode, the Au@Fc-Apt was further specifically bound to the bacteria, generating enhanced current signals for ultrasensitive detection of Staphylococcus aureus down to a single cell in phosphate buffer solution. Even in the complex milk samples, the sensor could detect as low as 10 CFU mL-1 of S. aureus without any complicated pretreatment except for 10-fold dilution. Moreover, the current response to the target bacteria was hardly affected by the coexisting multiple interfering bacteria, whose number is 30 times higher than the target, demonstrating the excellent selectivity of the sensor. Compared with most reported sandwich-type electrochemical sensors, this assay is more sensitive and more rapid, requiring less time (1.5 h) for the sensing interface construction. By virtue of its sensitivity, rapidity, selectivity, and cost-effectiveness, the sensor can serve as a universal detection platform for monitoring pathogenic bacteria in fields of food/public safety.

AntDAS-DDA: A New Platform for Data-Dependent Acquisition Mode-Based Untargeted Metabolomic Profiling Analysis with Advantage of Recognizing Insource Fragment Ions to Improve Compound Identification.

Data-dependent acquisition (DDA) mode in ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) can provide massive amounts of MS1 and MS/MS information of compounds in untargeted metabolomics and can thus facilitate compound identification greatly. In this work, we developed a new platform called AntDAS-DDA for the automatic processing of UHPLC-HRMS data sets acquired under the DDA mode. Several algorithms, including extracted ion chromatogram extraction, feature extraction, MS/MS spectrum construction, fragment ion identification, and MS1 spectrum construction, were developed within the platform. The performance of AntDAS-DDA was investigated comprehensively with a mixture of standard and complex plant data sets. Results suggested that features in complex sample matrices can be extracted effectively, and the constructed MS1 and MS/MS spectra can benefit in compound identification greatly. The efficiency of compound identification can be improved by about 20%. AntDAS-DDA can take full advantage of MS/MS information in multiple sample analyses and provide more MS/MS spectra than single sample analysis. A comparison with advanced data analysis tools indicated that AntDAS-DDA may be used as an alternative for routine UHPLC-HRMS-based untargeted metabolomics. AntDAS-DDA is freely available at http://www.pmdb.org.cn/antdasdda.

[Effect of mogroside VI on acute liver injury induced by sepsis in mice and related mechanisms].

OBJECTIVE: To study the effect of mogroside VI (MVI) on acute liver injury induced by sepsis in mice and its possible mechanisms. Methods A total of 60 male C57BL/6 mice were randomly divided into five groups: sham-operation, model, low-dose MVI (25 mg/kg), high-dose MVI (100 mg/kg), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) inhibitor (100 mg/kg MVI+30 mg/kg PGC-1α inhibitor SR-18292), with 12 mice in each group. Cecal ligation and puncture were performed to establish a mouse model of sepsis. The drugs were given by intraperitoneal injection after the model was established, once a day for 3 consecutive days. ELISA was used to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Colorimetry was used to measure the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in liver tissue. Hematoxylin-eosin staining was used to observe liver histopathological changes. Liver mitochondrial respiratory function was measured, and mitochondrial respiratory control rate was calculated. RT-PCR was used to measure the copy number of mitochondrial DNA (mtDNA) in liver tissue and the mRNA expression levels of PGC-1α, nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) in liver tissue. Western blot was used to measure the protein expression levels of PGC-1α, NRF-1, and TFAM in liver tissue. RESULTS: Compared with the sham-operation group, the model group had significant increases in the serum levels of ALT and AST and the content of MDA in liver tissue (P<0.05) and significant reductions in the activities of GSH-Px and SOD in liver tissue (P<0.05). The model group had also severe liver histopathological injury and significant reductions in the mitochondrial respiratory control rate, the copy number of mtDNA, and the mRNA and protein expression levels of PGC-1α, NRF-1, and TFAM in liver tissue (P<0.05). Compared with the model group, the high-dose group had significant reductions in the serum levels of ALT and AST and the content of MDA in liver tissue (P<0.05), significant increases in the activities of GSH-Px and SOD in liver tissue (P<0.05), significant improvement in liver histopathological injury, and significant increases in the mitochondrial respiratory control rate, the copy number of mtDNA, and the mRNA and protein expression levels of PGC-1α, NRF-1, and TFAM in liver tissue (P<0.05). There were no significant differences in the above indicators between the low-dose and model groups (P>0.05). The PGC-1α inhibitor SR-18292 significantly inhibited the intervention effect of high-dose MVI (P<0.05). CONCLUSIONS: MVI can effectively alleviate acute liver injury caused by sepsis in mice, possibly by enhancing mitochondrial biosynthesis mediated by PGC-1α.

Targeting the RhoA-ROCK pathway to regulate T-cell homeostasis in hypoxia-induced pulmonary arterial hypertension.

BACKGROUND: Hypoxic pulmonary arterial hypertension (PAH) is a crippling disease with limited therapeutic methods. The imbalance of T helper 17 cell (Th17)/regulatory T cell (Treg) plays an important role in the development of Hypoxic PAH. However, whether targeting the ras homolog family member A-Rho kinase (RhoA-ROCK) pathway (activation and inhibition) by lysophosphatidic acid (LPA) and fasudil (FSD) regulate T-cell homeostasis in Hypoxic PAH remain unknown. OBJECTIVE: To examine the effects of LPA and FSD on hypoxic pulmonary vascular remodeling and homeostasis of Th17/Treg cells in Hypoxic PAH. METHODS: Rats were exposed to hypoxia (10 ±â€¯0.5% O2) to induce Hypoxic PAH. The experiments consists of two parts. Forty rats were randomly divided into four groups (n = 10): normoxia group, normoxia + LPA group, hypoxia group and hypoxia + LPA group. Thirty rats were randomly divided into another three groups (n = 10): normoxia group, hypoxia group, and hypoxia + FSD group. Rats in normoxia + LPA group and hypoxia + LPA group were intraperitoneally injected 40 µg/kg LPA daily. Rats in hypoxia + FSD group were intraperitoneally injected 30 mg/kg fasudil daily. The effects of LPA and FSD on the development of hypoxic PAH and right ventricle (RV) hypertrophy, on pulmonary vascular remodeling, and on changes of Th17/Treg cells and levels of interleukin-17 (IL-17) and IL-10 were examined. RESULTS: PAH and RV hypertrophy occurred in rats exposed to hypoxia. LPA exacerbated hypoxic pulmonary vascular remodeling and FSD inhibited it. LPA increased Th17/Treg imbalance in peripheral blood and spleen. However, after treatment with FSD, hypoxic PAH rats showed an obvious reduction of Th17 cells as well as an increase of Treg cells. LPA increased the expression of phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) and reduced the p-STAT5 in peripheral blood and spleen in hypoxic PAH rats. The expression of p-STAT3 and p-STAT5 in hypoxic PAH rats treated with FSD showed opposite changes. LPA increased the expression of IL-17 and reduced the IL-10 in small intrapulmonary arteries and serum in hypoxic PAH. However, the expression of IL-17 and IL-10 in hypoxic PAH rats treated with FSD showed opposite changes. CONCLUSIONS: Activation and inhibition of RhoA-ROCK pathway by LPA and FSD modulated the homeostasis of Th17/Treg cells via regulating STAT3/STAT5 phosphorylation in hypoxic PAH. Thus, Apart from influence of pulmonary vascular remodeling, regulation of Th17/Treg homeostasis by RhoA-ROCK pathway play a key role in hypoxic PAH.

AntDAS: Automatic Data Analysis Strategy for UPLC-QTOF-Based Nontargeted Metabolic Profiling Analysis.

High-quality data analysis methodology remains a bottleneck for metabolic profiling analysis based on ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. The present work aims to address this problem by proposing a novel data analysis strategy wherein (1) chromatographic peaks in the UPLC-QTOF data set are automatically extracted by using an advanced multiscale Gaussian smoothing-based peak extraction strategy; (2) a peak annotation stage is used to cluster fragment ions that belong to the same compound. With the aid of high-resolution mass spectrometer, (3) a time-shift correction across the samples is efficiently performed by a new peak alignment method; (4) components are registered by using a newly developed adaptive network searching algorithm; (5) statistical methods, such as analysis of variance and hierarchical cluster analysis, are then used to identify the underlying marker compounds; finally, (6) compound identification is performed by matching the extracted peak information, involving high-precision m/z and retention time, against our compound library containing more than 500 plant metabolites. A manually designed mixture of 18 compounds is used to evaluate the performance of the method, and all compounds are detected under various concentration levels. The developed method is comprehensively evaluated by an extremely complex plant data set containing more than 2000 components. Results indicate that the performance of the developed method is comparable with the XCMS. The MATLAB GUI code is available from http://software.tobaccodb.org/software/antdas .

Aspirin alleviates cardiac fibrosis in mice by inhibiting autophagy.

Aspirin (ASA) is a cardioprotective drug with anti-cardiac fibrosis action in vivo. This study was aimed to clarify the anti-cardiac fibrosis action of ASA and the underlying mechanisms. Two heart injury models (injection of isoproterenol and ligation of the left anterior descending branch) were used in mice to induce cardiac fibrosis. The animals were treated with ASA (10 mg·kg-1·d-1, ig) for 21 and 14 d, respectively. ASA administration significantly improved cardiac function, and ameliorated heart damage and fibrosis in the mice. The mechanisms underlying ASA's anti-fibrotic effect were further analyzed in neonatal cardiac fibroblasts (CFs) exposed to hypoxia in vitro. ASA (0.5-5 mmol/L) dose-dependently inhibited the proliferation and Akt phosphorylation in the CFs. In addition, ASA significantly inhibited CF apoptosis, and decreased the levels of apoptosis markers (cleaved caspase 3 and Parp1), which might serve as a side effect of anti-fibrotic effect of ASA. Furthermore, ASA dose-dependently inhibited the autophagy in the CFs, as evidenced by the reduced levels of autophagy marker LC3-II. The autophagy inhibitor Pepstatin A (PepA) promoted the inhibitory effect of ASA on CF proliferation, whereas the autophagy inducer rapamycin rescued ASA-caused inhibition of CF proliferation, suggesting an autophagy-dependent anti-proliferative effect of ASA. Both p38 inhibitor SB203580 and ROS scavenger N-acetyl-cysteine (NAC) significantly decreased Akt phosphorylation in CFs in the basal and hypoxic situations, but they both significantly increased LC3-II levels in the CFs. Our results suggest that an autophagy- and p38/ROS-dependent pathway mediates the anti-cardiac fibrosis effect of ASA in CFs. As PepA and SB203580 did not affect ASA-caused inhibition of CF apoptosis, the drug combination will enhance ASA's therapeutic effects.

Sphingosylphosphorylcholine protects cardiomyocytes against ischemic apoptosis via lipid raft/PTEN/Akt1/mTOR mediated autophagy.

Autophagy, evoked by diverse stresses including myocardial ischemia/reperfusion (I/R), profoundly affects the development of heart failure. However, the specific molecular basis of autophagy remains to be elucidated. Here we report that sphingosylphosphorylcholine (SPC), a bioactive sphingolipid, significantly suppressed apoptosis and induced autophagy in cardiomyocytes. Blocking this SPC evoked autophagy by 3-methyladenine (3MA)-sensitized cardiomyocytes to serum deprivation-induced apoptosis. Subsequent studies revealed that SPC downregulated the phosphorylation of p70S6K and 4EBP1 (two substrates of mTOR) but enhanced that of JNK when inducing autophagy. We identified SPC as a switch for the activity of Akt1, a supposed upstream modulator of both mTOR and JNK. Furthermore, ß-cyclodextrin, which destroys membrane cholesterol, abolished the SPC-reduced phosphorylation of both Akt and PTEN, thus inhibiting SPC-induced autophagy. In conclusion, SPC is a novel molecule protecting cardiomyocytes against apoptosis by promoting autophagy. The lipid raft/PTEN/Akt1/mTOR signal pathway is the underlying mechanism and might provide novel targets for cardiac failure therapy.

[Value of blood lactic acid in evaluating disease severity and prognosis in children with sepsis].

OBJECTIVE: To investigate the value of blood lactic acid (BLA) in evaluating disease severity and prognosis in children with sepsis. METHODS: A total of 484 children with sepsis were enrolled and divided into common sepsis group (n=310), severe sepsis group (n=105), and septic shock group (n=69). BLA level was measured before treatment, and the results of BLA re-examination after early fluid resuscitation were collected for children with septic shock and a BLA level of >2 mmol/L. RESULTS: The BLA level increased with the increasing severity of sepsis. The analysis of the receiver operating characteristic curve showed that the cut-off value of BLA for the diagnosis of septic shock was 2.25 mmol/L, with a sensitivity of 82.6% and a specificity of 79.8%. The fatality rates in the BLA ≤1 mmol/L, BLA 1.1-2 mmol/L, BLA 2.1-4 mmol/L, and BLA >4 mmol/L groups were 8.5%, 9.4%, 27.2%, and 67.6%, respectively, and the risk of death in the BLA >4 mmol/L group was 22.4 times that in the BLA ≤1 mmol/L group. In children with septic shock who had a BLA level of >2 mmol/L before treatment and whose BLA levels were ≤2 mmol/L or >2 mmol/L after resuscitation, the fatality rates were 33.3% and 69.2%, respectively. CONCLUSIONS: BLA can be used to evaluate disease severity and prognosis in children with sepsis, and a BLA level of 2.25 mmol/L has a high value in diagnosing septic shock. Early resuscitation helps BLA level return to normal and can improve the prognosis of children with septic shock.

Influence of human myasthenia gravis thymus on the differentiation of human cord blood stem cells in SCID mice.

The normal thymus contributes to T lymphocytes differentiation and induction of tolerance to self-antigens. Myasthenia gravis (MG) is characterized by abnormal thymic hyperplasia. To assess the potential influence of MG-thymus on the differentiation of T lymphocytes differentiation, we used the MG-thymus transplanted severe combined immunodeficiency (SCID) mice model to evaluate the human cord blood stem cells differentiation. Thymus fragments from MG patient and human cord blood stem cells were transplanted into SCID mice successively. SCID mice were observed to develop sustained human T lymphocytes and a functional anti-tumor immune. The levels of various T cell subsets in SCID mice with MG-thymus were different from that of control group. Among that, the frequency of CD4(+)CD25(+) T cells was significant lower in SCID mice with MG-thymus. The deficiency of CD4(+)CD25(+) T cells seens to contribute to the pathogenesis of MG.

Design, synthesis, and evaluation of novel ferrostatin derivatives for the prevention of HG-induced VEC ferroptosis.

Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated cell death. It has been shown that high glucose (HG) could induce ferroptosis in vascular endothelial cells (VECs), consequently contributing to the development of various diseases. This study synthesized and evaluated a series of novel ferrostatin-1 (Fer-1) derivatives fused with a benzohydrazide moiety to prevent HG-induced VEC ferroptosis. Several promising compounds showed similar or improved inhibitory effects compared to positive control Fer-1. The most effective candidate 12 exhibited better protection against erastin-induced ferroptosis and high glucose-induced ferroptosis in VECs. Mechanistic studies revealed that compound 12 prevented mitochondrial damage, reduced intracellular ROS accumulation, upregulated the expression of GPX4, and decreased the amounts of ferrous ion, LPO and MDA in VECs. However, compound 12 still exhibited undesirable microsomal stability like Fer-1, suggesting the need for further optimization. Overall, the present findings highlight ferroptosis inhibitor 12 as a potential lead compound for treating ferroptosis-associated vascular diseases.

Systemic lupus erythematosus with multicentric reticulohistiocytosis: A case report.

BACKGROUND: Multicentric reticulohistiocytosis (MRH)/systemic lupus erythematosus (SLE) overlap syndrome is an uncommon disease in the clinic and is diagnosed through characteristic clinical manifestations, histopathology, and immunopathology. Here, we report the case of a 30-year-old woman with SLE who developed MRH. CASE SUMMARY: A 30-year-old woman with a history of polyarthritis for the past 12 years had multiple skin nodules on her body for 10 years, including the sacrococcygeal area, dorsum of the hands, interphalangeal joint of the feet and sternoclavicular joint. The histopathology of a biopsy of the distal interphalangeal joint of the hands revealed granulomatous inflammation, fibrous hyperplasia with ground-glass degeneration, inflammatory cell exudation and focal necrosis. The immunohistochemical stains showed positive staining for CD68 and negative staining for S100 and acid-fast staining. The patient was diagnosed with SLE with MRH. Her symptoms were improved after a combined treatment of prednisone, hydroxychloroquine and cyclophosphamide. CONCLUSION: MRH/SLE overlap syndrome is difficult to diagnose and treat. Cyclophosphamide may be an alternative choice for the treatment of MRH.

Complement-related proteins in crustacean immunity.

As an important part of innate immune system, complement system is widely involved in defense response and immune regulation, and plays an important biological role. The complement system has been deeply studied. More than 30 complement-related molecules and three major complement-activation pathways have been identified in vertebrates. Crustacean animals do not have complement system. There are only some complement-related proteins in crustaceans which are important for host defense. In this review, we summarize the current knowledge about complement-related proteins in crustaceans, and their functions in crustacean immunity. We also make a comparation of the crustacean pro-phenoloxidase activating system and the mammalian complement system. This review provides a better understanding of the evolution and function of complement-related proteins in crustaceans.

Preoperative small airway dysfunction is associated with skeletal muscle loss in early-stage non-small cell lung cancer.

BACKGROUND: Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. METHODS: There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. RESULTS: This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5 ± 8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p = 0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p = 0.046; for FEF50%, r = -0.142, p = 0.008; and for FEF25-75%, r=-0.124, p = 0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p > 0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p = 0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P = 0.041) were associated with postoperative complications. CONCLUSION: Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.

Lower subcutaneous fat index predicts bone metastasis in breast cancer.

BACKGROUND: Bone metastases affect 50% to 70% of breast cancer (BC) patients and have a high mortality rate. Adipose tissue loss plays a pivotal role in the progression of cancer. OBJECTIVE: This study aims to evaluate the prognostic value of adipose tissue for bone metastasis in BC patients. METHODS: 517 BC patients were studied retrospectively. Patients' characteristics before the surgery were collected. Quantitative measurements of the subcutaneous fat index (SFI) were performed at the level of the eleventh thoracic vertebra. In order to adjust for the heterogeneity between the low SFI and high SFI groups, propensity score matching (PSM) was used. The Kaplan-Meier method was used to estimate the 5-year bone metastatic incidence. The prognostic analysis was performed with the Cox regression models. RESULTS: Compared with the patients without bone metastasis, the patients with bone metastasis had reduced SFI levels. In addition, Kaplan-Meier analysis revealed that patients with low SFI were more likely to develop bone metastases. The independent predictive value of SFI for bone metastases was confirmed by Cox regression analysis. The survival analysis was repeated after PSM with a 1:1 ratio, yielding similar results (P< 0.05). CONCLUSIONS: SFI is an independent predictor of bone metastasis in BC patients.