Abstract In this study, echinacoside was extracted from Cistanche tubulosa (Schenk) R. Wight, and its protective effect on liver injury in sepsis rats was investigated. Forty-five rats were randomly divided into control, sepsis and echinacoside groups, 15 rats in each group. The sepsis model was established in sepsis and echinacoside groups. In echinacoside group, the rats were treated with echinacoside at 1 h before modeling. At 24 h after modeling, compared with sepsis group, in echinacoside group the serum aspartate aminotransferase and alanine aminotransferase levels were decreased, the liver injury score and hepatocyte apoptosis rate were decreased, the serum monocyte chemoattractant protein-1, tumor necrosis factor α, interleukin 6 and interleukin 1β levels were decreased, the liver tissue catalase, superoxide dismutase and glutathione peroxidase levels were increased, the liver tissue malondialdehyde level was decreased, and the liver tissue nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein expression levels were increased. The difference of all above comparisons was significant (P < 0.05). In conclusion, echinacoside can inhibit the inflammatory response, activate the Nrf2/HO-1 signal pathway, and reduce the oxidative stress, thus alleviating the liver injury in sepsis rats.

The mutations of breast cancer susceptibility gene 1 (BRCA1) play an important role in inherited breast cancers. Thus, the sensitive assay of the BRCA1 gene is extremely important for disease diagnosis and human health. Herein, a fast, sensitive and selective assay technique has been constructed based on fluorescent copper nanoclusters (CuNCs). The CuNCs were successfully formed with poly(AT-TA) double stranded DNA (dsDNA) as template. In the absence of the target, a strong red emission was observed under 365 nm ultraviolet (UV) lamp and a big fluorescence response was obtained. However, in the presence of BRCA1 gene, there was only weak red emission and a low response signal was produced because of the target-proximity induced quenching of the fluorescence of CuNCs. The linear range for the BRCA1 gene assay was 2-600 nM, and the limit of detection was 2 nM. The assay technique showed good selectivity, good stability and satisfactory recoveries for the detection of BRCA1 gene in diluted serum samples. Moreover, by integrating a UV lamp and a smartphone, the fluorescence sensor would be transferred to a microfluidic chip, providing a prospective application in point-of-care for monitoring breast cancer risk.

Abstract Background Currently, only a few studies have described the general characteristics of patients with primary Sjögren's syndrome (pSS) who tested negatives for anti-SSA and anti-SSB antibodies. We aimed to further investigate the clinical characteristics of these patients in a large sample. Methods Data from patients with pSS who were treated at a tertiary hospital in China between 2013 and 2022 were retrospectively analyzed. Clinical characteristics of the patients were compared between those with and without anti-SSA and anti-SSB antibody negativity. Factors associated with anti-SSA and anti-SSB negativity were identified by logistic regression analysis. Results Overall, 934 patients with pSS were included in this study, among whom 299 (32.0%) tested negative for anti-SSA and anti-SSB antibodies. Compared with patients testing positive for anti-SSA or anti-SSB antibodies, that testing negative for the two antibodies had a lower proportion of females (75.3% vs. 90.6%, p < 0.001) and thrombocytopenia (6.7% vs. 13.6%, p = 0.002), but a higher proportion of abnormal Schirmer I tests (96.0% vs. 89.1%, p = 0.001) and interstitial lung disease (ILD) (59.2% vs. 28.8%, p = 0.001). Anti-SSA and anti-SSB negativity was positively associated with male sex (odds ratio [OR] = 1.86, 95% confidence interval [CI]: 1.05, 3.31), abnormal Schirmer I tests (OR = 2.85, 95% CI: 1.24, 6.53), and ILD (OR = 2.54, 95% CI: 1.67, 3.85). However, it was negatively related to thrombocytopenia (OR = 0.47, 95% CI: 0.24, 0.95). Conclusion Approximately one third of pSS patients had anti-SSA and anti-SSB negativity. pSS patients testing negative for anti-SSA and anti-SSB showed a higher risk of abnormal Schirmer I tests and ILD, but a lower risk of thrombocytopenia.

SUMMARY: The atlanto-occipital joint is composed of the superior fossa of the lateral masses of the atlas (C1) and the occipital condyles. Congenital Atlanto-occipital fusion (AOF) involves the osseous union of the base of the occiput (C0) and the atlas (C1). AOF or atlas occipitalization/assimilation represents a craniovertebral junction malformation (CVJM) which can be accompanied by other cranial or spinal malformations. AOF may be asymptomatic or patients may experience symptoms from neural compression as well as limited neck movement. The myodural bridge (MDB) complex is a dense fibrous structure that connects the suboccipital muscular and its related facia to the cervical spinal dura mater, passing through both the posterior atlanto-occipital and atlanto-axial interspaces. It is not known if atlas occipitilization can induce structural changes in the MDB complex and its associated suboccipital musculature. The suboccipital region of a cadaveric head and neck specimen from an 87-year-old Chinese male having a congenital AOF malformation with resultant changes to the MDB complex was observed. After being treated with the P45 plastination method, multiple slices obtained from the cadaveric head and neck specimen were examined with special attention paid to the suboccipital region and the CVJM. Congenital atlanto-occipital fusion malformations are defined as partial or complete fusion of the base of the occiput (C0) with the atlas (C1). In the present case of CVJM, unilateral fusion of the left occipital condyle with the left lateral mass of C1 was observed, as well as posterior central fusion of the posterior margin of the foramen magnum with the posterior arch of C1. Also noted was a unilateral variation of the course of the vertebral artery due to the narrowed posterior atlanto-occipital interspace. Surprisingly, complete agenesis of the rectus capitis posterior minor (RCPmi) and the obliques capitis superior (OCS) muscles was also observed in the plastinated slices. Interestingly, the MDB, which normally originates in part from the RCPmi muscle, was observed to originate from a superior bifurcation within an aspect of the nuchal ligament. Therefore, the observed changes involving the MDB complex appear to be an effective compensation to the suboccipital malformations.

RESUMEN: La articulación atlanto-occipital está compuesta por las caras articulares superiores de las masas laterales del atlas (C1) y los cóndilos occipitales. La fusión atlanto-occipital congénita (FAO) implica la unión ósea de la base del occipucio (C0) y el atlas (C1). La FAO u occipitalización/asimilación del atlas representa una malformación de la unión craneovertebral (MUCV) que puede presentar otras malformaciones craneales o espinales. La FAO puede ser asintomática o los pacientes pueden experimentar síntomas de compresión neural así como movimiento limitado del cuello. El complejo del puente miodural (PMD) es una estructura fibrosa densa que conecta el músculo suboccipital y su fascia relacionada con la duramadre espinal cervical, pasando a través de los espacios intermedios atlanto-occipital posterior y atlanto-axial. No se sabe si la occipitilización del atlas puede inducir cambios estructurales en el complejo PMD y en la musculatura suboccipital. Se observó en la región suboccipital de un espécimen cadavérico, cabeza y cuello de un varón chino de 87 años con una malformación congénita de FAO con los cambios resultantes en el complejo PMD. Se examinaron múltiples cortes obtenidos de la muestra de cabeza y cuello después de ser tratados con el método de plastinación P45, con especial atención a la región suboccipital y la MUCV. Las malformaciones congénitas por fusión atlanto-occipital se definen como la fusión parcial o completa de la base del occipucio (C0) con el atlas (C1). En el presente caso de MUCV se observó la fusión unilateral del cóndilo occipital izquierdo con la masa lateral izquierda de C1, así como fusión posterior central del margen posterior del foramen magnum con el arco posterior de C1. También se observó una variación unilateral del curso de la arteria vertebral por el estrechamiento del espacio interatlanto-occipital posterior. Se observó además agenesia completa de los músculos Rectus capitis posterior minor (RCPmi) y oblicuos capitis superior (OCS) en los cortes plastinados. Curiosamente, se observó que el MDB, que normalmente se origina en parte del músculo RCPmi, se origina en una bifurcación superior dentro de un aspecto del ligamento nucal. Por lo tanto, los cambios observados en el complejo PMD parecen ser una compensación de las malformaciones suboccipitales.

A series of novel betulin-28-hydrazone derivatives (7a-7o) were synthesized. All compounds were evaluated for their in vitro cytotoxicities in four human carcinoma cells (HepG2, MCF-7, HCT-116 and A549). Among them, compound 7l displayed the most potent cytotoxicity with an IC50 (concentration of the tested compound that inhibits 50% of cell growth) value of 7.37 ± 0.38 μM against MCF-7 cells. The preliminary cellular mechanism studies indicated that compound 7l could induce MCF-7 cells apoptosis. The above findings indicated that compound 7l may be used as a lead compound for antitumor agents with improved efficacy.

Abstract Introduction: The objective of this study was to investigate the effect of mivacurium in the application of fast-track anesthesia for transthoracic device closure of ventricular septal defects (VSDs) in children. Methods: The data of 108 children who underwent transthoracic device closure of VSDs from December 2018 to June 2020 were recorded and analyzed. All children were divided into group M (mivacurium group, n=55) and group C (cisatracurium group, n=53) according to the different muscle relaxant drug used. Results: No statistically significant differences in general preoperative data, intraoperative hemodynamic changes, or the incidence of adverse reactions were noted between the two groups (P>0.05). However, the intubation condition rating of children in group M was better than that in group C. The onset time, duration of clinical action and recovery index of the muscle relaxant, postoperative mechanical ventilation duration, and length of intensive care unit stay in group M were significantly lower than those in group C (P<0.05). Conclusion: It is safe and feasible to use mivacurium as a muscle relaxant in children undergoing fast-track cardiac anesthesia during transthoracic device closure of VSDs.

Abstract Lactic acid bacteria (LAB) can produce extracellular polysaccharides that can be used as thickeners, emulsifiers, and gels in foods. The immobilization technology can effectively simplify and improve the separation and regeneration of extracellular polysaccharides. In this study, six strains of LAB, including the extracellular polysaccharide-producing strain Lactobacillus plantarum, were screened. The different immobilized carriers of sodium alginate, agar, gelatin-glutaraldehyde, and carrageenan were assessed for fermentation by these six LAB. Different diameters of beads were selected, and the optimum culture temperature, carrier concentration, and inoculum volume were evaluated. The results showed that the agar-embedding method was the best immobilization method and the optimum process conditions were as follows: 3% inoculum of L. plantarum, 30 g/L of agar as immobilization carrier with a particle diameter of 1 cm, and fermentation at 37 °C for 24 h. Through orthogonal experiments, the maximum exopolysaccharide (EPS) yield obtained was 1489.9 mg/L.

Abstract To study the maternal and neonatal outcomes of pregnancy complicated with Systemic Lupus Erythematosus (SLE). Clinical data of 84 pregnant women complicated with SLE were collected. All patients were divided into the different groups based on the pregestational status of SLE, SLE status during pregnancy and the type of medicine administration respectively. The incidence rates of pregnancy loss and preterm labor in the pregestational and gestational stable SLE groups were significantly lower and the incidence rate of full-term labor was considerably higher than those in the active SLE groups. In the pregestational stable SLE group, the incidence of PIH was significantly lower than that in the active SLE group. The incidence of PIH and FGR in the gestational active SLE group was dramatically higher than that in the gestational stable SLE group. Among 84 women, 56 (66.7%) received cesarean section, 18 (21.4%) vaginal delivery and 10 (11.9%) labor induction. The status of SLE is intimately correlated with maternal and neonatal outcomes. PIH is a major complication of active SLE and associated with adverse pregnancy outcomes. SLE can cause congenital fetal injury, especially congenital heart block.

Abstract Characterizations of rat mandibular second molar extraction socket with significantly different buccal and lingual alveolar ridge width remain unclear. Objective: To observe alterations in the alveolar ridge after extraction of mandibular second molars, and to examine processes of alveolar socket healing in an experimental model of alveolar ridge absorption and preservation. Methodology: Eighteen Wistar rats were included and divided into six groups regarding healing time in the study. Bilateral mandibular second molars were extracted. The rats with tooth extraction sockets took 0, 1.5, 2, 3, 4 and 8 weeks of healing. Histological observation, tartrate-resistant acidic phosphatase (TRAP) staining, Masson’s trichrome staining, immunohistochemical staining and micro-computed tomography (micro-CT) were applied to estimate alterations in the alveolar ridge. Results: Different buccal and lingual alveolar ridge width led to different height loss. Lingual wall height (LH) decreased significantly two weeks after tooth extraction. Buccal wall height rarely reduced its higher ridge width. From two to eight weeks after extraction, bone volume (BV/TV), density (BMD), and trabecular thickness (Tb.Th) progressively increased in the alveolar socket, which gradually decreased in Tb.Sp and Tb.N. LH showed no significant change during the same period. Osteogenic marker OCN and OPN increased during bone repair from two to eight weeks. The reduced height of the lingual wall of the tooth extraction socket was rarely repaired in the later repair stage. Osteoclast activity led to absorption of the alveolar ridge of the alveolar bone wall within two weeks after operation. We observed positive expression of EMMPRIN and MMP-9 in osteoclasts that participated in the absorption of the spire region. Conclusion: Extraction of rat mandibular second molars may help the study of alveolar ridge absorption and preservation. The EMMPRIN-MMP-9 pathway may be a candidate for further study on attenuating bone resorption after tooth extraction.

ABSTRACT We examined differences in slaughter performance and meat quality of Honghe yellow cattle of different ages. We randomly selected nine Honghe bulls for slaughter at 12 (12M), 36 (36M), and 60 (60M) months of age. There were significant differences in antemortem live weight, carcass weight, and net weight among the three groups, all of which increased with age. Backfat thickness in 36M (4.77±0.25 mm) and 60M (5.50±0.50 mm) was significantly higher than in 12M (3.00±0.00 mm), and the loin-eye area in 60M (68.02±16.02) was higher than in 12M (27.01±1.89). There was no significant difference in the pH value of the month-old group. Compared with 12M (29.33±4.93%) and 60M (23.87±5.08%), the cooking loss of meat in 36M (36.50±5.07%) was significantly higher; meanwhile, a* value was also the highest in 36M (22.39±1.34), the protein and fat content of muscle in 12M was lower, while the content of meat in 60M was lower. There was no significant difference in muscle ash, Ca, and P contents; the total amino acid and essential amino acid contents of 36M were higher than those of 12M and 60M, and the unsaturated fatty acids of meat in 12M were higher than those in 36M and 60M. The change of age has a certain influence on the slaughter performance and meat quality of Honghe yellow cattle.

ABSTRACT Purpose: This study investigated the effects of oral administration of Clostridium butyricum (C. butyricum) on inflammation, oxidative stress, and gut flora in rats with hepatic ischemia reperfusion injury (HIRI). Methods: The rats from C. butyricum group were given C. butyricum for 5 days. Then, hepatic ischemia for 30 min and reperfusion for 6 h were performed in all the rats. After the animals were sacrificed, alanine transaminase (ALT), aspartate aminotransferase (AST), lipopolysaccharide (LPS) in serum, short-chain fatty acids (SCFAs), and gut microbiota composition in feces, and malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), Toll-like receptor 4 (TLR4), nuclear factor-kappa Bp65 (NF-κBp65) and histological analysis in the liver were performed. Results: The rats given C. butyricum showed decreased ALT, AST, LPS, and MDA; improved GSH and histological damage; changes in SCFAs; declined TNF-α, IL-6, TLR4, and pNF-κBp65/NF-κBp65; and changes in the gut microbial composition, which decreased the Firmicutes/Bacteroidetes ratio and increased the relative abundance (RA) of probiotics. Conclusions: C. butyricum supplementation protected against HIRI by regulating gut microbial composition, which contributed to the decreased LPS and attenuation of inflammation and oxidative stress. These indicate C. butyricum may be a potent clinical preoperative dietary supplement for HIRI.

Recombinant human peroxiredoxin-5 (hPRDX5), isolated from anti-cancer bioactive peptide (ACBPs), shows a homology of 89% with goat peroxiredoxin-5 (gPRDX5) and is reported to display anti-tumor activity in vivo. Herein, we explored the effect of hPRDX5 and the responsible mechanism in treating pancreatic cancer. Tumor-bearing mice were randomly divided into normal PBS group and treatment group (n=5; 10 mg/kg hPRDX5). Flow cytometry was employed to examine lymphocytes, myeloid-derived suppressor cell subsets, and the function proteins of natural killer (NK) cells in peripheral blood, spleen, and tumor tissues of mice. Western blot was used to measure the protein expressions of the key nodes in TLR4-MAPK-NF-κB signaling pathway. The rate of tumor suppression was 57.6% at a 10 mg/kg dose in orthotopic transplanted tumor mice. Moreover, the population of CD3+CD4+T cells, NK cells, and CD3+CD8+T cells was significantly increased in the tumor tissue of the hPRDX5 group, while the proportion of granulocytic-myeloid-derived suppressor cells decreased slightly. In addition, after treatment with hPRDX5, the percentage of NK cells in blood increased more than 4-fold. Our findings indicated that hPRDX5 effectively suppressed pancreatic cancer possibly via the TLR4-MAPK-NF-κB signaling cascade; hence hPRDX5 could be a prospective immunotherapy candidate for treating pancreatic cancer.

ABSTRACT Purpose: To investigate the role of renal denervation (RDN) on endogenous ouabain (EO) secretion in spontaneously hypertensive rats (SHR). Methods: Sixteen 12-week-old male SHR were randomly separated into the renal denervation group (RDNX group) and sham operation group (sham group), and eight age-matched Wistar Kyoto rats (WKY) were served as control group. EO concentrations, the Na+- K+-ATPaseactivity, and the expression of Na+-K+-ATPase were assessed. Results: EO levels in serum, kidneys and hypothalamus of sham group were higher than in RDNX group (p < 0.05). Renal Na+-K+-ATPase activity subjected to denervation surgery showed significantly reduction when compared with the sham groups (p < 0.05). A positive correlation existed between norepinephrine (NE) content and Na+-K+-ATPase activity in the kidney (r2 = 0.579). Renal Na+-K+-ATPase α1 subunit mRNA expression was down-regulated in the RDNX group compared with the sham group (P < 0.05), while renal Na+-K+-ATPase α1 subunit mRNA expression was no statistical significance between the groups (P = 0.63). Immunohistochemical analysis showed that there were significant differences in the renal expression of Na+-K+-ATPasebetween the three groups (P < 0.05). Conclusions: These experiments demonstrate that RDN exerted an anti-hypertensive effect with reduction of EO levels and Na+-K+-ATPase activity and Na+-K+-ATPase α1 subunit expression of kidney in SHR.

Abstract Gut bacterial β-glucuronidase (GUS) can reactivate xenobiotics that exert enterohepatic circulation- triggered gastrointestinal tract toxicity. GUS inhibitors can alleviate drug-induced enteropathy and improve treatment outcomes. We evaluated the inhibitory effect of Polygonum cuspidatum Siebold & Zucc. and its major constituents against Escherichia coli GUS (EcGUS), and characterized the inhibitory mechanism of each of the components. Trans-resveratrol 4’-O-β-D-glucopyranoside (HZ-1) and (-)-epicatechin gallate (HZ-2) isolated from P. cuspidatum were identified as the key components and potent inhibitors. These two components displayed strong to moderate inhibitory effects on EcGUS, with Ki values of 9.95 and 1.95 μM, respectively. Results from molecular docking indicated that HZ-1 and HZ-2 could interact with the key residues Asp163, Ser360, Ile 363, Glu413, Glu504, and Lys 568 of EcGUS via hydrogen bonding. Our findings demonstrate the inhibitory effect of P. cuspidatum and its two components on EcGUS, which supported the further evaluation and development of P. cuspidatum and its two active components as novel candidates for alleviating drug-induced damage in the mammalian gut.

Abstract Objective: To investigate the impact of recombinant human interferon α1b (rhIFNα1b) treatment in infants hospitalized with lower respiratory tract infections on subsequent wheezing. Methods: The clinical data of infants (n = 540) with viral pneumonia, wheezy bronchitis, or bronchiolitis hospitalized in 19 Chinese hospitals from June 2009 to June 2015 were retrospectively analyzed. The parameters relevant to wheezing episodes within the last year were collected by telephone and questionnaires. The rhIFNα1b treatment group (n = 253) and control group (n = 287) were compared in terms of wheezing episodes within the last year. Moreover, the wheezing group (95 cases) and non-wheezing group (445 cases) were compared. Results: Out of 540 cases, 95 (17.6%) experienced wheezing episodes, 13.8% (35/253) cases treated with rhIFNα1b, and 20.9% (60/287) cases without rhIFNα1b experienced wheezing episodes within the last year. The rhIFNα1b treatment significantly improved wheezing episodes within the last year, compared with the control peers (p = 0.031). Single-factor regression showed statistically significant differences between the wheezing and non-wheezing groups in terms of age, rhIFNα1b use, childhood and family history of allergy, housing situation, and feeding history (p < 0.05). Binary logistic regression showed a childhood history of allergy (OR = 2.14, p = 0.004), no rhIFNα1b use (OR = 1.70, p = 0.028), and living in a crowded house (OR = 1.92, p = 0.012) might be risk factors of subsequent wheezing. Accordingly, breastfeeding (OR = 0.44, p = 0.008) and hospitalization age of 1-year-old (OR = 0.58, p = 0.024) were protective factors. Conclusions: Early use of rhIFNα1b in infants hospitalized with lower respiratory tract infections and breastfeeding could prevent subsequent wheezing. Living in a crowded house could promote subsequent wheezing.