An Observational Study on the Clinical Characteristics and Prognosis of Patients With Interstitial Lung Disease Secondary to Dermatomyositis and Antisynthetase Syndrome.

Objective: Identify the clinical characteristics and prognostic factors in patients with idiopathic inflammatory myopathy (IIM) combined with interstitial lung disease (ILD). Methods: IIM-ILD patients who were hospitalized at Guangxi Medical University from January 2017 to December 2022 were retrospectively analyzed and classified as having dermatomyositis (DM)-ILD or -ILD. Clinical and laboratory results were analyzed. Results: There were 39 males and 111 females, the mean age of disease onset was 50.4 ± 12.3 years, and the median disease duration was 3 months (range: 1-6). Ninety-seven patients had DM-ILD, and 53 had ASS-ILD. The DM-ILD group had 72% positivity for the anti-MDA5 antibody and 5.2% positivity for the anti-Mi-2 antibody; the ASS-ILD group had 67.9% positivity for the anti-Jo-1 antibody and 17% positivity for the anti-EJ antibody. Muscle symptoms, skin ulcers, rash, rapidly progressing interstitial lung disease (RP-ILD), and elevated levels of serum carcinoembryonic antigen were more common in DM-ILD patients (all p < 0.05). However, pericardial effusion and pleural effusion, elevated creatinine kinase, and elevated C-reactive protein were more common in ASS-ILD patients. After a median follow-up of 15.5 months, there were more deaths in the DM-ILD group (42.3% vs. 13.2%, p < 0.001). Multivariate Cox regression analysis showed that RP-ILD, dyspnea, and the usual interstitial pneumonia type of ILD had negative associations with overall survival (OS), and arthralgia had a positive association with OS (all p < 0.05). Conclusion: DM-ILD patients were more prone to secondary RP-ILD and skin ulcers, had milder symptoms of myositis and less severe serositis, and had lower survival rates than the ASS-ILD patients. RP-ILD, dyspnea, and the usual interstitial pneumonia type of ILD had adverse effects on prognosis, but arthralgia was a protective factor.

Screening bioactive compounds from Fangji Huangqi decoction for treating rheumatoid arthritis via COX-2 magnetic ligand fishing combined with in vivo validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Fangji Huangqi Decoction (FHD) is a classical Chinese compound formula for treating rheumatoid arthritis (RA) with satisfactory effects. FHD is reputed for its ability to tonify qi with strengthening exterior, and dispel wind while removing dampness, but its mechanisms and bioactive compounds for treating RA remain unclear. AIM OF THE STUDY: The aim of this study was to explore the key target and bioactive compounds that were responsible for FHD-mediated improvements in RA. MATERIALS AND METHODS: Using network pharmacology, we discovered that cyclooxygenase-2 (COX-2) was the key target of FHD against RA. We utilized a ligand fishing technique with COX-2 immobilized magnetic beads to recognize the bioactive components that act on COX-2. Then we carried out an in vitro assay of COX-2 enzyme inhibition and in vivo assay of carrageenan-induced inflammation and collagen-induced arthritis (CIA) to validate the bioactive effects of these captured ingredients. In the CIA assay, micro-CT, hematoxylin‒eosin staining and safranin-O/fast green staining were employed to assess the influence of the captured ligand on bone damage, pathological injury and cartilage destruction, respectively. Immunohistochemistry (IHC) and enzyme-linked immunosorbent assays (ELISAs) were used to detect the expression of COX-2 target in the ankle joint. interleukin-6 (IL-6) levels in the serum were also detected by ELISA. Molecular docking was used to reveal the binding mechanism of the COX-2 protein and the captured ligand. RESULTS: Eleven ligands, including tetrandrine, fangchinoline, cyclanoline, licochalcone B, ononin, calycosin and liquiritin, were specifically bound to the COX-2 protein, as determined by ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS), seven of which were present at high levels. One ligand, tetrandrine, not only had a great inhibitory effect on COX-2 enzyme activity but also significantly reduced carrageenan-induced inflammation. In the CIA assay, middle- and high-dose tetrandrine (25 and 50 mg/kg) had effects comparable to those of FHD and celecoxib on ameliorating RA symptoms in CIA mice via the COX-2 target. Furthermore, compared with the low-dose tetrandrine group (12.5 mg/kg), the FHD group exhibited significantly lower arthritis index scores and serum IL-6 expression, although the content of tetrandrine in FHD extract solution was approximately 0.1% of that in the low-dose tetrandrine group. CONCLUSIONS: Hence, we inferred that tetrandrine was the main bioactive component responsible for the effects of FHD against RA by suppressing the expression of the COX-2 protein and inhibiting the enzyme catalytic activity of COX-2. The reason for these effects may be that tetrandrine can interact with the residue Tyr385 of COX-2, the enzymatic catalytic site of COX-2 to transform arachidonic acid (AA) to prostaglandin E2 (PGE2), and thereby reduce the production of prostaglandins and inflammatory metabolites. Moreover, in addition to tetrandrine, FHD contains other compounds that could supplement the activity of tetrandrine when FHD was used to treat RA, which is manifested the "multi-component" characteristic of how Traditional Chinese Medicine formulas treat diseases.

Nomogram for the preoperative prediction of Ki-67 expression and prognosis in stage IA lung adenocarcinoma based on clinical and multi-slice spiral computed tomography features.

OBJECTIVE: This study developed and validated a nomogram utilizing clinical and multi-slice spiral computed tomography (MSCT) features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma. Additionally, we assessed the predictive accuracy of Ki-67 expression levels, as determined by our model, in estimating the prognosis of stage IA lung adenocarcinoma. MATERIALS AND METHODS: We retrospectively analyzed data from 395 patients with pathologically confirmed stage IA lung adenocarcinoma. A total of 322 patients were divided into training and internal validation groups at a 6:4 ratio, whereas the remaining 73 patients composed the external validation group. According to the pathological results, the patients were classified into high and low Ki-67 labeling index (LI) groups. Clinical and CT features were subjected to statistical analysis. The training group was used to construct a predictive model through logistic regression and to formulate a nomogram. The nomogram's predictive ability and goodness-of-fit were assessed. Internal and external validations were performed, and clinical utility was evaluated. Finally, the recurrence-free survival (RFS) rates were compared. RESULTS: In the training group, sex, age, tumor density type, tumor-lung interface, lobulation, spiculation, pleural indentation, and maximum nodule diameter differed significantly between patients with high and low Ki-67 LI. Multivariate logistic regression analysis revealed that sex, tumor density, and maximum nodule diameter were significantly associated with high Ki-67 expression in stage IA lung adenocarcinoma. The calibration curves closely resembled the standard curves, indicating the excellent discrimination and accuracy of the model. Decision curve analysis revealed favorable clinical utility. Patients with a nomogram-predicted high Ki-67 LI exhibited worse RFS. CONCLUSION: The nomogram utilizing clinical and CT features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma demonstrated excellent performance, clinical utility, and prognostic significance, suggesting that this nomogram is a noninvasive personalized approach for the preoperative prediction of Ki-67 expression.

Geniposide ameliorates brain injury in mice with intracerebral hemorrhage by inhibiting NF-κB signaling.

BACKGROUND: Neuroinflammation and oxidative stress are critical players in intracerebral hemorrhage (ICH). Geniposide is an active component of Gardenia that has anti-inflammatory effects. This study focused on the roles and mechanisms of geniposide in ICH. METHODS: ICH was established by injecting collagenase IV into C57BL/6 mice. To determine the functions of geniposide and NF-κB inhibition in ICH model mice, geniposide (1, 25, or 50 mg/kg) or PDTC (a NF-κB inhibitor) was administered. Neurological functions were assessed with the modified neurological severity score (mNSS) test. Hematoxylin and eosin staining were performed to identify pathological changes. IL-1ß and TNF-α levels were estimated with ELISA kits. NF-κB p65 localization was determined by immunofluorescence staining. Oxidative stress was analyzed by measuring ROS levels. RESULTS: Geniposide alleviated cerebral edema and neurological deficits. Geniposide inhibited neuroinflammation and oxidative stress after ICH, and the inhibitory effects were enhanced by NF-κB inhibition. Additionally, geniposide inhibited NF-κB signaling. CONCLUSION: Geniposide alleviates brain injury by suppressing inflammation and oxidative stress damage in experimental ICH models by inhibiting NF-κB signaling.

Activation of APE1 modulates Nrf2 protected against acute liver injury by inhibit hepatocyte ferroptosis and promote hepatocyte autophagy.

BACKGROUND: Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) plays a crucial role in DNA base excision repair, cell apoptosis, cell signaling, and the regulation of transcription factors through redox modulation and the control of reactive oxygen species (ROS). However, the connection between APE1 and acute liver injury (ALI) remains enigmatic. This study aims to unravel the molecular mechanisms underlying ALI and shed light on the role of APE1 in this context. METHOD: We induced acute liver injury (ALI) in mice by lipopolysaccharide/D-galactosamine (LPS/GalN) and intervened with the APE1 inhibitor E3330. We examined the expression of APE1 in ALI mice and ALI patient tissues after E3330 intervention, Additionally, we measured hepatic oxidative stress, ferroptosis, and autophagy marker proteins and genes. In establishing an AML-12 liver cell injury model, we utilized the Nrf2 activator tert-butylhydroquinone (TBHQ) as an intervention and examined APE1, Nrf2, ferroptosis-related proteins, and autophagy marker proteins and mRNA. RESULTS: Both ALI patients and ALI mice exhibited reduced APE1 expression levels. After E3330 intervention, there was a significant exacerbation of liver injury, oxidative stress, and a reduction in the expression of proteins, including GPX4, X-CT, ATG3, ATG5, and LC3 (LC3I/II). Consistent results were also observed in AML-12 cells. With TBHQ intervention, Nrf2 expression increased, along with the expression of proteins associated with iron death and autophagy. Mechanistically, APE1 activation regulates Nrf2 to inhibit ferroptosis and promote autophagy in hepatocytes. CONCLUSION: The data suggest that APE1 is a pivotal player in ALI, closely linked to its regulation of Nrf2. Strategies involving APE1 activation to modulate Nrf2, thereby inhibiting hepatocyte ferroptosis and promoting autophagy, may represent innovative therapeutic approaches for ALI. Additionally, tert-butylhydroquinone (TBHQ) holds significant promise in the treatment of acute liver injury.

Myofibrillar proteins' intermolecular interaction weakening and degradation: Are they mainly responsible for the tenderization of meat containing l-arginine, l-lysine, or/and NaCl?

This study explored the effects of l-arginine, l-lysine, and NaCl alone and in combination on the tenderness of porcine meat. Arg, Lys, and NaCl alone improved the tenderness, decreased the cooking loss, and increased the myofibrillar fragmentation index (MFI) of porcine meat; Both Arg and Lys cooperated with NaCl to better achieve this effect. Furthermore, Arg/Lys collaborated with NaCl to increase muscle fiber swelling and moisture content of the meat and promoted the extraction of main myofibrillar proteins. FT-IR revealed that Arg, Lys, or NaCl alone or in combination caused changes in protein-water interactions. Western blotting revealed varying degrees of meat protein degradation in all cases, but the results did not well coincide with those of shear force and the MFI. Therefore, the weakening of intermolecular forces between myofibrillar proteins was considered the main reason for meat tenderization under the present study conditions.

A novel selective ERK1/2 inhibitor, Laxiflorin B, targets EGFR mutation subtypes in non-small-cell lung cancer.

Extracellular regulated protein kinases 1/2 (ERK1/2) are key members of multiple signaling pathways, including the ErbB axis. Ectopic ERK1/2 activation contributes to various types of cancer, especially drug resistance to inhibitors of RTK, RAF and MEK, and specific ERK1/2 inhibitors are scarce. In this study, we identified a potential novel covalent ERK inhibitor, Laxiflorin B, which is a herbal compound with anticancer activity. However, Laxiflorin B is present at low levels in herbs; therefore, we adopted a semi-synthetic process for the efficient production of Laxiflorin B to improve the yield. Laxiflorin B induced mitochondria-mediated apoptosis via BAD activation in non-small-cell lung cancer (NSCLC) cells, especially in EGFR mutant subtypes. Transcriptomic analysis suggested that Laxiflorin B inhibits amphiregulin (AREG) and epiregulin (EREG) expression through ERK inhibition, and suppressed the activation of their receptors, ErbBs, via a positive feedback loop. Moreover, mass spectrometry analysis combined with computer simulation revealed that Laxiflorin B binds covalently to Cys-183 in the ATP-binding pocket of ERK1 via the D-ring, and Cys-178 of ERK1 through non-inhibitory binding of the A-ring. In a NSCLC tumor xenograft model in nude mice, Laxiflorin B also exhibited strong tumor suppressive effects with low toxicity and AREG and EREG were identified as biomarkers of Laxiflorin B efficacy. Finally, Laxiflorin B-4, a C-6 analog of Laxiflorin B, exhibited higher binding affinity for ERK1/2 and stronger tumor suppression. These findings provide a new approach to tumor inhibition using natural anticancer compounds.

ROS-Responsive Prodrug Micelle Co-Delivery System for Synergistic Antiatherosclerotic Therapy.

Tanshinone IIA (TS-IIA) and salvianic acid A (SAA) are the main pharmacological active constituents of Danshen, which exhibit potent effects on atherosclerosis. A combination of TS-IIA and SAA might exert a synergistic antiatherosclerotic effect. However, the opposite solubility profiles of TS-IIA and SAA might lead to difficulty in achieving a synergistic combined effect of the two active components. Therefore, in this work, we fabricated a ROS-responsive prodrug micelle for the codelivery of TS-IIA and SAA (TS-IIA-PM) by self-assembling amphiphilic block copolymer PEG5000-SAA/PLA10000-APBA. The amphiphilic polymer was characterized by 1H NMR, FTIR, and alizarin red S competition tests. The ROS responsiveness of TS-IIA-PM was evidenced by time-course monitoring of particle size and morphology changes and drug release behavior in the presence of 1 mM H2O2. We found TS-IIA-PM was stable according to its critical micelle concentration and the unchanged particle sizes in 10% FBS for 7 days. The results of in vitro and in vivo tests revealed that TS-IIA-PM was safe and biocompatible. Furthermore, it was observed that TS-IIA and prodrug micelle could produce synergistic antiatherosclerotic effect based on the results of the antioxidant study, which was further confirmed by a series of pharmocodynamics studies, such as in vitro DiI-oxLDL uptake study, oil red O staining, cholesterol efflux study, inflammatory cytokine analysis, in vivo CD68 immunostaining, and lipid disposition staining studies. Collectively, TS-IIA-PM holds great potential for the safe and efficient codelivery of TS-IIA and SAA for synergistic antiatherosclerosis.

Effect of different concentrations of gellan gum with/without 0.50% basil essential oil on the physicochemical properties of gellan gum-rice bran oil coating emulsions and their application in egg preservation.

This work investigated the effects of different concentrations (0.10 %, 0.15 % or 0.20 %, w/v) of gellan gum (GG) with/without 0.50 % (v/v) basil essential oil (BEO) on physicochemical properties of gellan gum-rice bran oil (GG-RBO) emulsions. The results showed that GG-RBO emulsions with 0.15 % or 0.20 % GG were more stable than GG-RBO emulsion with 0.10 % GG (as evidenced by higher apparent viscosity and absolute zeta potential, but smaller average particle size and lower turbidity), thus displaying better coating performances (as evidenced by bigger contact angle but lower moisture content). The presence of BEO further improved their stability and coating performances. Coating with GG-BRO or GG-RBO-BEO emulsion with 0.15 % GG significantly delayed the increase in weight loss, and the decrease in haugh unit, yolk index and albumen pH of eggs during 42 days storage; moreover, GG-RBO-BEO emulsion caused lower total aerobic plate count. Therefore, GG-RBO, especially GG-RBO-BEO emulsion has potential in egg preservation.

The Biomechanical Characteristics of Swallowing in Tracheostomized Patients with Aspiration following Acquired Brain Injury: A Cross-Sectional Study.

Objectives: Investigate the biomechanical characteristics in tracheostomized patients with aspiration following acquired brain injury (ABI) and further explore the relationship between the biomechanical characteristics and aspiration. Methods: This is a single-center cross-sectional study. The tracheostomized patients with aspiration following ABI and age-matched healthy controls were recruited. The biomechanical characteristics, including velopharynx (VP) maximal pressure, tongue base (TB) maximal pressure, upper esophageal sphincter (UES) residual pressure, UES relaxation duration, and subglottic pressure, were examined by high-resolution manometry and computational fluid dynamics simulation analysis. The penetration−aspiration scale (PAS) score was evaluated by a videofluoroscopic swallowing study. Results: Fifteen healthy subjects and fifteen tracheostomized patients with aspiration following ABI were included. The decreased VP maximal pressure, increased UES residual pressure, and shortened UES relaxation duration were found in the patient group compared with the control group (p < 0.05). Furthermore, the subglottic pressure significantly decreased in patients (p < 0.05), while no significant difference was found in TB maximal pressure between groups (p > 0.05). In addition, in the patient group, VP maximal pressure (rs = −0.439; p = 0.015), UES relaxation duration (rs = −0.532; p = 0.002), and the subglottic pressure (rs = −0.775; p < 0.001) were negatively correlated with the PAS score, while UES residual pressure (rs = 0.807; p < 0.001) was positively correlated with the PAS score (p < 0.05), the correlation between TB maximal pressure and PAS score (rs = −0.315; p = 0.090) did not reach statistical significance. Conclusions: The biomechanical characteristics in tracheostomized patients with aspiration following ABI might manifest as decreased VP maximal pressure and subglottic pressure, increased UES residual pressure, and shortened UES relaxation duration, in which VP maximal pressure, UES relaxation duration, subglottic pressure, and UES residual pressure were correlated with aspiration.

6-Shogaol inhibits the proliferation, apoptosis, and migration of rheumatoid arthritis fibroblast-like synoviocytes via the PI3K/AKT/NF-κB pathway.

BACKGROUND: Fibroblast-like synoviocytes (FLSs) are essential for joint destruction in rheumatoid arthritis (RA). 6-Shogaol, a phenolic extract isolated from ginger, has been found to have potential benefits in the treatment of diverse inflammatory and immune disorders. However, the role of 6-shogaol in RA has yet to be explored. PURPOSE: To reveal the effect of 6-shogaol on RA FLSs and MH7A cells and to investigate the molecular mechanism of 6-shogao in RA. METHODS: We performed MTT, EdU, cell apoptosis, cell migration and invasion, RT-qPCR, western blot analysis, and immunofluorescence to elucidate the effect of 6-shogaol on the proliferation, apoptosis, and migration of RA FLSs and MH7A cells and revealed its modulation of the PI3K/AKT/NF-κB pathway. The in vivo therapeutic effect of 6-shogaol was verified in mice with collagen-induced arthritis (CIA). RESULTS: 6-Shogaol suppressed proliferation, migration, and invasion, and induced apoptosis in RA FLSs and MH7A cells. 6-Shogaol also reduced the production of TNF-α, IL-1ß, IL-6, IL-8, MMP-2, and MMP-9. Molecular analysis revealed that 6-shogaol inhibited the PI3K/AKT/NF-κB pathway by activating PPAR-γ. Treatment with 6-shogaol ameliorated joint destruction of mice with CIA. CONCLUSION: This study revealed that 6-shogaol inhibited proliferation, migration, invasion, cytokine, and MMPs production, and induced apoptosis in RA FLSs via the PI3K/AKT/NF-κB pathway, providing a new natural potential drug for future RA treatments.

Gancao Fuzi decoction regulates the Th17/Treg cell imbalance in rheumatoid arthritis by targeting Foxp3 via miR-34a.

ETHNOPHARMACOLOGICAL RELEVANCE: During the Eastern Han Dynasty, Zhang Zhongjing first recorded the Gancao Fuzi decoction (GCFZD) formula in the "Synopsis of the Golden Chamber", which is reportedly an effective and safe treatment for rheumatoid arthritis (RA). However, the mechanism underlying the observed improvement in the T helper 17 (Th17)/regulatory T (Treg) cell imbalance in RA obtained with GCFZD has not been reported. AIM OF THE STUDY: This study aimed to demonstrate whether GCFZD ameliorated RA by modulating the Th17/Treg imbalance in RA mice. MATERIALS AND METHODS: Collagen was used to induce a model of collagen-induced arthritis (CIA) in mice. GCFZD was administered by gavage, and the arthritis index score, imaging and histopathological changes of the ankle joints, and the levels of the immunoglobulin G (IgG) class antibodies and proinflammatory factors in serum were determined. In addition, the frequencies of Th17 and Treg cells, the levels of relevant transcription factors and functional factors and the miR-34a gene in the spleen and the levels of interleukin-17A (IL-17A) and IL-10 in serum were determined. RESULTS: GCFZD significantly reduced the arthritis score, improved joint swelling and bone damage, reduced the pathological score, and decreased the serum levels of IgG class antibody (IgG and IgG2a) and proinflammatory factor [tumour necrosis factor-alpha (TNF-α), IL-1ß and IL-6]. Moreover, the Th17-cell proportion, the expression level of the Th17-specific transcription factor retinoic acid-related orphan receptor γt (RORγt) and functional factor IL-17A in the spleen, and the serum IL-17A level were decreased, whereas the Treg cell proportion, expression levels of the Treg-specific transcription factor forkhead box P3 (Foxp3) and functional factor IL-10 in the spleen, and the serum IL-10 level were increased. Furthermore, GCFZD inhibited miR-34a gene expression while promoting Foxp3 protein expression. CONCLUSIONS: The findings of this study demonstrate the therapeutic effect of GCFZD on mice with CIA, and the mechanism is related to an improvement in the Th17/Treg cell imbalance by targeting Foxp3 via miR-34a.

Biomechanical mechanism of reduced aspiration by the Passy-Muir valve in tracheostomized patients following acquired brain injury: Evidences from subglottic pressure.

Objective: Aspiration is a common complication after tracheostomy in patients with acquired brain injury (ABI), resulting from impaired swallowing function, and which may lead to aspiration pneumonia. The Passy-Muir Tracheostomy and Ventilator Swallowing and Speaking Valve (PMV) has been used to enable voice and reduce aspiration; however, its mechanism is unclear. This study aimed to investigate the mechanisms underlying the beneficial effects of PMV intervention on the prevention of aspiration. Methods: A randomized, single-blinded, controlled study was designed in which 20 tracheostomized patients with aspiration following ABI were recruited and randomized into the PMV intervention and non-PMV intervention groups. Before and after the intervention, swallowing biomechanical characteristics were examined using video fluoroscopic swallowing study (VFSS) and high-resolution manometry (HRM). A three-dimensional (3D) upper airway anatomical reconstruction was made based on computed tomography scan data, followed by computational fluid dynamics (CFD) simulation analysis to detect subglottic pressure. Results: The results showed that compared with the non-PMV intervention group, the velopharynx maximal pressure (VP-Max) and upper esophageal sphincter relaxation duration (UES-RD) increased significantly (P < 0.05), while the Penetration-Aspiration Scale (PAS) score decreased in the PMV intervention group (P < 0.05). Additionally, the subglottic pressure was successfully detected by CFD simulation analysis, and increased significantly after 2 weeks in the PMV intervention group compared to the non-PMV intervention group (P < 0.001), indicating that the subglottic pressure could be remodeled through PMV intervention. Conclusion: Our findings demonstrated that PMV could improve VP-Max, UES-RD, and reduce aspiration in tracheostomized patients, and the putative mechanism may involve the subglottic pressure. Clinical trial registration: [http://www.chictr.org.cn], identifier [ChiCTR1800018686].

Individual effects of rosemary extract and green tea polyphenols on the physicochemical properties of soybean oil-myosin emulsion with l-arginine or l-lysine.

This study aimed to investigate the individual effects of rosemary extract and green tea polyphenols on the stability of the soybean oil-myosin emulsions with l-arginine or l-lysine. The results showed that l-arginine or l-lysine increased the physical stability of emulsion in all cases. In the presence of metallic cations, rosemary extract increased the physical stability, while green tea polyphenols decreased the physical stability. l-Arginine or l-lysine retarded the lipid and protein oxidation of emulsion in the absence of metallic cations during storage, but accelerated it in the presence of metallic cations. The two antioxidants delayed l-arginine- or l-lysine-induced lipid and protein oxidation in the presence of metallic cations. The results provide a new method for improving the physical and chemical stability of emulsion sausages in which l-arginine or l-lysine is applied to improve the quality attributes of emulsion sausage.

Effects of manual washing with three alkaline sterilizing agent solutions on egg quality during storage.

This study aimed to investigate the abundance of microorganisms and quality of eggs washed with different washings (tap water, 0.03% calcium hypochlorite solution, 0.25% hydrogen peroxide solution, or 1% sodium percarbonate solution) and unwashed for 28-day storage. The results showed that the washing significantly decreased the abundance of microorganisms in all cases. Washing with one of the three alkaline sterilizing agent solutions significantly inhibited the deterioration of egg quality (evidenced by lower weight loss, air cell depth, albumen pH, yolk pH, and total volatile base nitrogen, but higher Haugh unit and yolk index) during storage, while washing with tap water showed opposite effects. The texture profile analysis and high-resolution scanning electron microscopy observation showed that all washings had slight negative effects on eggshell quality (eggshell breaking strength and microstructure), and washing with the alkaline sterilizing agent solution had no additional effects. The results might be attractive to egg preservation industry.

The c.612A>G mutation of MC4R affects constitutive activity and signaling in domestic goats.

As a key gene for balancing energy and regulating feeding behavior, MC4R is relevant to the growth of ruminants. In this presentation, a highly conserved c.612A>G site in the coding sequence (CDS) of MC4R has been selected during a selective sweep analysis of 35 Yiling goats and 20 other wild goats. This site mutation results in an amino acid change from Ile to Met. The genotyping analysis of the c.612A>G site revealed that the A allele was the dominant allele in the domestic goat populations, while the wild goat individuals only had the G allele. For a better understanding of the biological significance of this site, we examined the protein localization and signal detection to explain the function of the two MC4R receptors. The results showed that both the M204 and I204 receptors can normally localize on the membrane. When stimulating the M204 type without α-MSH, it was defective at the level of basal cAMP and decreased significantly against the I204 type. In contrast, the signaling capacity of the M204 receptor was also lower than that of I204 under the stimulation of α-MSH. In the ERK1/2 pathway, stimulating MC4R with NDP-α-MSH, both the M204 and I204 receptors had normal pERK1/2 levels. These results indicate that the p.I204M mutation may change the function by damaging the constitutive activity and signaling, and thus may regulate goats' appetite. This study has potential application for rearing domestic goats.

Shedding of SARS-CoV-2 for 85 Days in COVID-19 Patients With Type 2 Diabetes Mellitus and Lung Metastasis: A Case Report.

Background: COVID-19 (coronavirus disease 2019) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seriously endangers people's lives. The variation in SARS-CoV-2 makes the research and development of vaccines and specific drugs particularly important. However, the prevention and diagnosis of COVID-19 cannot be underestimated in the control of the epidemic. Case Presentation: We introduced a 65-year-old female patient who was diagnosed with COVID-19. The SARS-CoV-2 nucleic acid test result of this patient was positive again during treatment. It took 85 days from the first symptom to the final cure. According to the known reports, she is currently the patient with the longest virus shedding in Sichuan Province, China. Due to the patient's special condition, she was treated in four hospitals before and after, and she was diagnosed with type 2 diabetes mellitus (T2DM) and right lung metastatic adenocarcinoma. We fully introduced the patient's epidemiological history, diagnosis, testing, and treatment process. The patient was finally discharged from the hospital under the treatment of antiviral, hypoglycaemic, anti-anxiety, and a combination of Chinese and Western medicine. Conclusions: The epidemic is still rampant, and we should not relax our efforts in the prevention and control of viruses. For the elderly, especially those who are suffering from complications or vulnerable to diseases, it is recommended to extend the observation time. Additionally, medical workers should pay attention to the mental state of patients.

Application of MSCT characteristic nomogram model in predicting invasion of pancreatic solid pseudopapillary neoplasms.

OBJECTIVE: To evaluate the value of multi-slice computed tomography (MSCT) characteristic nomogram model in predicting invasion of pancreatic solid pseudopapillary neoplasms (pSPN). METHODS: From January 2016 to January 2021, the clinical characteristics, pathology and imaging data of 114 patients with pSPN were retrospectively analyzed. 42 cases were classified in invasive group while 72 cases in non-invasive group. The tumor location, shape, growth pattern, growth angle, margin calcification, floating cloud sign, annular enhancement, pancreatic and bile duct dilation, distal pancreatic atrophy, capsule, cystic degeneration and cystic to solid ratio between the two groups were analyzed. The maximum diameter and the CT value of the solid parts in the lesion were measured. RESULTS: There were significant differences in tumor shape, growth pattern, margin, annular enhancement, capsule, CT value in arterial phase and venous phase (P < 0.05). There was no significant difference in tumor location, growth angle, calcification, floating cloud sign, pancreatic and bile duct dilation, distal pancreatic atrophy, cystic degeneration, cystic-solid ratio and CT value of lesion in plain scan (P > 0.05). The independent predictors of pSPN invasion included growth pattern, annular enhancement, capsule, and CT value of lesion in arterial phase. A nomogram model was successfully established to predict the invasion of pSPN. The area under the receiver operating characteristic curve was 0.888, and the calibration prediction curve was in good agreement with the standard curve. CONCLUSION: The nomogram model based on MSCT features has high application value in preoperative prediction of tumor invasion of pancreatic solid pseudopapillary neoplasms.

MicroRNA-146a inhibition promotes total neurite outgrowth and suppresses cell apoptosis, inflammation, and STAT1/MYC pathway in PC12 and cortical neuron cellular Alzheimer's disease models.

This study aimed to explore the effect of microRNA (miR)-146a inhibition on regulating cell apoptosis, total neurite outgrowth, inflammation, and STAT1/MYC pathway in Alzheimer's disease (AD). PC12 and cortical neuron cellular AD models were constructed by Aß1-42 insult. For the former model, nerve growth factor (NGF) stimulation was previously conducted. miR-146a inhibitor and negative-control (NC) inhibitor were transfected into the two cellular AD models, and then cells were named miR-inhibitor group and NC-inhibitor group, respectively. After transfection, cell apoptosis, total neurite outgrowth, supernatant inflammation cytokines, and STAT1/MYC pathway were detected. miR-146a expression was similar between PC12 cellular AD model and control cells (NGF-stimulated PC12 cells), while miR-146a expression was increased in cortical neuron cellular AD model compared with control cells (rat embryo primary cortical neurons). In both PC12 and cortical neuron cellular AD models, miR-146a expression was reduced in miR-inhibitor group compared with NC-inhibitor group after transfection. Furthermore, cell apoptosis was attenuated, while total neurite outgrowth was elevated in miR-inhibitor group compared with NC-inhibitor group. As for supernatant inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-17 levels were lower in miR-inhibitor group than in NC-inhibitor group. Additionally, STAT1 and c-Myc mRNA and protein expressions were attenuated in miR-inhibitor group compared with NC-inhibitor group. In conclusion, miR-146a potentially represented a viable therapeutic target for AD.

MicroRNA-146a inhibition promotes total neurite outgrowth and suppresses cell apoptosis, inflammation, and STAT1/MYC pathway in PC12 and cortical neuron cellular Alzheimer's disease models

This study aimed to explore the effect of microRNA (miR)-146a inhibition on regulating cell apoptosis, total neurite outgrowth, inflammation, and STAT1/MYC pathway in Alzheimer's disease (AD). PC12 and cortical neuron cellular AD models were constructed by Aβ1-42 insult. For the former model, nerve growth factor (NGF) stimulation was previously conducted. miR-146a inhibitor and negative-control (NC) inhibitor were transfected into the two cellular AD models, and then cells were named miR-inhibitor group and NC-inhibitor group, respectively. After transfection, cell apoptosis, total neurite outgrowth, supernatant inflammation cytokines, and STAT1/MYC pathway were detected. miR-146a expression was similar between PC12 cellular AD model and control cells (NGF-stimulated PC12 cells), while miR-146a expression was increased in cortical neuron cellular AD model compared with control cells (rat embryo primary cortical neurons). In both PC12 and cortical neuron cellular AD models, miR-146a expression was reduced in miR-inhibitor group compared with NC-inhibitor group after transfection. Furthermore, cell apoptosis was attenuated, while total neurite outgrowth was elevated in miR-inhibitor group compared with NC-inhibitor group. As for supernatant inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-17 levels were lower in miR-inhibitor group than in NC-inhibitor group. Additionally, STAT1 and c-Myc mRNA and protein expressions were attenuated in miR-inhibitor group compared with NC-inhibitor group. In conclusion, miR-146a potentially represented a viable therapeutic target for AD.