RopB-regulated SpeB cysteine protease degrades extracellular vesicles-associated streptolysin O and bacterial proteins from group A Streptococcus.

Extracellular vesicles (EVs) can be released from gram-positive bacteria and would participate in the delivery of bacterial toxins. Streptococcus pyogenes (group A Streptococcus, GAS) is one of the most common pathogens of monomicrobial necrotizing fasciitis. Spontaneous inactivating mutation in the CovR/CovS two-component regulatory system is related to the increase of EVs production via an unknown mechanism. This study aimed to investigate whether the CovR/CovS-regulated RopB, the transcriptional regulator of GAS exoproteins, would participate in regulating EVs production. Results showed that the size, morphology, and number of EVs released from the wild-type strain and the ropB mutant were similar, suggesting RopB is not involved in controlling EVs production. Nonetheless, RopB-regulated SpeB protease degrades streptolysin O and bacterial proteins in EVs. Although SpeB has crucial roles in modulating protein composition in EVs, the SpeB-positive EVs failed to trigger HaCaT keratinocytes pyroptosis, suggesting that EVs did not deliver SpeB into keratinocytes or the amount of SpeB in EVs was not sufficient to trigger cell pyroptosis. Finally, we identified that EV-associated enolase was resistant to SpeB degradation, and therefore could be utilized as the internal control protein for verifying SLO degradation. This study revealed that RopB would participate in modulating protein composition in EVs via SpeB-dependent protein degradation and suggested that enolase is a potential internal marker for studying GAS EVs.

Incidence and contributing factors of non-root canal treated teeth with chronic fatigue root fracture: A cross-sectional study.

BACKGROUND/PURPOSE: Chronic fatigue root fracture describes a root fracture in a non-root canal treated (non-RCT) tooth. This study aimed to report the incidence and contributing factors of non-RCT teeth with chronic fatigue root fracture in a Taiwanese population. METHODS: This cross-sectional study included teeth extracted at Taipei Veterans General Hospital in Taiwan between 2018 and 2019. The reasons for extractions were recorded and included vertical and horizontal root fractures (VRF and HRF). Comparisons of clinical factors between teeth with fatigue VRF and teeth with fatigue HRF were performed by chi-square or Fisher exact test, where appropriate. RESULTS: Of the 4207 extracted teeth examined, 263 (6.25%) had tooth fracture. Thirty-two non-RCT teeth had chronic fatigue root fracture, including 16 with VRF and 16 with HRF. The incidence was 0.76% (32/4207). The occurrence of chronic fatigue root fracture was higher in males (83.9%). The mean age of the 31 patients with chronic fatigue root fracture was 71.7 ± 13.1 years. More than half of these teeth had intact crowns with severe attrition. The fatigue VRF occurred more frequently in molars (P = 0.003), in roots with a long oval cross-section (P = 0.037), and in terminal teeth (P = 0.013) than the fatigue HRF. CONCLUSION: The incidence of chronic fatigue root fracture is 0.76%. Both VRF and HRF occur mainly in aged males, in posterior teeth with attrition, and in teeth without restoration. Tooth position, cross-section root morphology, and terminal tooth are contributing factors related to chronic fatigue root fracture.

RopB represses the transcription of speB in the absence of SIP in group A Streptococcus.

RopB is a quorum-sensing regulator that binds to the SpeB-inducing peptide (SIP) under acidic conditions. SIP is known to be degraded by the endopeptidase PepO, whose transcription is repressed by the CovR/CovS two-component regulatory system. Both SIP-bound RopB (RopB-SIP) and SIP-free RopB (apo-RopB) can bind to the speB promoter; however, only RopB-SIP activates speB transcription. In this study, we found that the SpeB expression was higher in the ropB mutant than in the SIP-inactivated (SIP*) mutant. Furthermore, the deletion of ropB in the SIP* mutant derepressed speB expression, suggesting that apo-RopB is a transcriptional repressor of speB Up-regulation of PepO in the covS mutant degraded SIP, resulting in the down-regulation of speB We demonstrate that deleting ropB in the covS mutant derepressed the speB expression, suggesting that the speB repression in this mutant was mediated not only by PepO-dependent SIP degradation but also by apo-RopB. These findings reveal a crosstalk between the CovR/CovS and RopB-SIP systems and redefine the role of RopB in regulating speB expression in group A Streptococcus.

Missense mutation of c.635 T > C in CAPN3 impairs muscle injury repair in a Limb-Girdel Muscular Dystropy Model.

Limb-girdle muscular dystrophy recessive 1 (LGMDR1), previously known as LGMD2A, is a specific LGMD caused by a gene mutation encoding the calcium-dependent neutral cysteine protease calpain-3 (CAPN3). In our study, the compound heterozygosity with two missense variants c.635 T > C (p.Leu212Pro) and c.2120A > G (p.Asp707Gly) was identified in patients with LGMDR1. However, the pathogenicity of c.635 T > C has not been investigated. To evaluate the effects of this novel likely pathogenic variant to the motor system, the mouse model with c.635 T > C variant was prepared by CRISPR/Cas9 gene editing technique. The pathological results revealed that a limited number of inflammatory cells infiltrated the endomyocytes of certain c.635 T > C homozygous mice at 10 months of age. Compared with wild-type mice, motor function was not significantly impaired in Capn3 c. 635 T > C homozygous mice. Western blot and immunofluorescence assays further indicated that the expression levels of the Capn3 protein in muscle tissues of homozygous mice were similar to those of wild-type mice. However, the arrangement and ultrastructural alterations of the mitochondria in the muscular tissues of homozygous mice were confirmed by electron microscopy. Subsequently, muscle regeneration of LGMDR1 was simulated using cardiotoxin (CTX) to induce muscle necrosis and regeneration to trigger the injury modification process. The repair of the homozygous mice was significantly worse than that of the control mice at day 15 and day 21 following treatment, the c.635 T > C variant of Capn3 exhibited a significant effect on muscle regeneration of homozygous mice and induced mitochondrial damage. RNA-sequencing results demonstrated that the expression levels of the mitochondrial-related functional genes were significantly downregulated in the mutant mice. Taken together, the results of the present study strongly suggested that the LGMDR1 mouse model with a novel c.635 T > C variant in the Capn3 gene was significantly dysfunctional in muscle injury repair via impairment of the mitochondrial function.

Inhibitory Effect of Astragalus Polysaccharide on Premetastatic Niche of Lung Cancer through the S1PR1-STAT3 Signaling Pathway.

As a common malignant tumor, the morbidity and mortality of lung cancer have been rising in recent years. The concept of "premetastatic niche" may lead to a revolutionary change in antitumor metastasis therapeutic strategies. Traditional Chinese medicine with multitargets and lower poisonous agents may be a potentially effective means to intervene in the "premetastatic niche (PMN)" to prevent and treat tumor metastasis. Astragalus polysaccharide (APS) is a substance with strong immune activity in Astragalus membranaceus that has excellent biological activities such as immunomodulation, anti-inflammatory, and antitumor. In this study, we constructed a tumor lung metastasis animal model to explore the intervention mechanism of APS on the premetastatic niche. We found that APS inhibited the formation of the lung premetastatic niche and inhibited the recruitment of myeloid-derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and gene expression of S1PR1, STAT3, and p-STAT3 in the S1PR1/STAT3 signaling pathway were suppressed by APS. In line with the above findings, our results confirmed that APS may inhibit the accumulation of MDSCs in the premetastatic niche through the intervention of the S1PR1-STAT3 signaling pathway to achieve the antitumor effect.

The Bacterial Markers of Identification of Invasive CovR/CovS-Inactivated Group A Streptococcus.

Necrotizing fasciitis is a severe infectious disease that results in significant mortality. Streptococcus pyogenes (group A Streptococcus, GAS) is one of the most common bacterial pathogens of monomicrobial necrotizing fasciitis. The early diagnosis of necrotizing fasciitis is crucial; however, the typical cutaneous manifestations are not always presented in patients with GAS necrotizing fasciitis, which would lead to miss- or delayed diagnosis. GAS with spontaneous inactivating mutations in the CovR/CovS two-component regulatory system is significantly associated with destructive diseases such as necrotizing fasciitis and toxic shock syndrome; however, no specific marker has been used to identify these invasive clinical isolates. This study evaluated the sensitivity and specificity of using CovR/CovS-controlled phenotypes to identify CovR/CovS-inactivated isolates. Results showed that the increase of hyaluronic acid capsule production and streptolysin O expression were not consistently presented in CovS-inactivated clinical isolates. The repression of SpeB is the phenotype with 100% sensitivity of identifying in CovS-inactivated isolates among 61 clinical isolates. Nonetheless, this phenotype failed to distinguish RopB-inactivated isolates from CovS-inactivated isolates and cannot be utilized to identify CovR-inactivated mutant and RocA (Regulator of Cov)-inactivated isolates. In this study, we identified and verified that PepO, the endopeptidase which regulates SpeB expression through degrading SpeB-inducing quorum-sensing peptide, was a bacterial marker to identify isolates with defects in the CovR/CovS pathway. These results also inform the potential strategy of developing rapid detection methods to identify invasive GAS variants during infection. IMPORTANCE Necrotizing fasciitis is rapidly progressive and life-threatening; if the initial diagnosis is delayed, deep soft tissue infection can progress to massive tissue destruction and toxic shock syndrome. Group A Streptococcus (GAS) with inactivated mutations in the CovR/CovS two-component regulatory system are related to necrotizing fasciitis and toxic shock syndrome; however, no bacterial marker is available to identify these invasive clinical isolates. Inactivation of CovR/CovS resulted in the increased expression of endopeptidase PepO. Our study showed that the upregulation of PepO mediates a decrease in SpeB-inducing peptide (SIP) in the covR mutant, indicating that CovR/CovS modulates SIP-dependent quorum-sensing activity through PepO. Importantly, the sensitivity and specificity of utilizing PepO to identify clinical isolates with defects in the CovR/CovS pathway, including its upstream RocA regulator, were 100%. Our results suggest that identification of invasive GAS by PepO may be a strategy for preventing severe manifestation or poor prognosis after GAS infection.

Effectiveness of home-based telerehabilitation programs on functional capacity and cardiac function in elderly heart failure patients: A prospective longitudinal study.

Decreased functional capacity and reduced cardiac function were the main symptoms in patients with heart failure (HF) and the incidence increases with advanced age. The guidelines recommend that exercise training should be considered for medically stable HF outpatients. Studies have confirmed that exercise can improve functional capacity, prognosis, and reduced hospitalization rates; however, very few studies have investigated the elderly. It is not clear whether exercise could be feasible in elderly HF. The aim of this study was to evaluate the effect of the 6-month heart failure post-acute care program focused on home-based cardiac telerehabilitation (HCTR) on functional capacity, cardiac function, and readmission rates in HF patients. A prospective longitudinal study was conducted. Study duration was from January 2018 to December 2019. HF patients with a left ventricular ejection fraction <40% and age ≧65 years were included and divided into intervention (n = 40) and control group (n = 41). We arranged a 6-month heart failure post-acute care program that included outpatient cardiac rehabilitation and home exercise for the intervention group. The response to home exercise was followed by telemonitor. The exercise parameters were recorded on the HF health management mobile application system platform by each patient and daily transmission to hospital's cloud database as HCTR, usual care program for the control group. Information such as general data, laboratory data, six-minute walk test, cardiac function, and admission record was collected from all patients. Eighty one patients between the ages of 65 and 92 completed the study. The mean age was 73.3 ± 5.0 and 75.6 ± 6.0 years in control and intervention group, respectively. The intervention group showed a statistically significant improvement in functional capacity, percentage change in the of six-minute walk distance (51.2% vs 17.7%, P < .05, 95% confidence interval -45.9 to -6.3). Left ventricular ejection fraction increased by 7.7%, which corresponds to 25.6% in relative terms (P < .05, 95% confidence interval -7.8 to -0.5). The readmission rate was 4.6% in the intervention group. Six months of post-acute HF focused on HCTR programs was safe, improved functional capacity, cardiac function, and decreased readmission rate in elderly patients with HF patients.

Total flavonoids of Oxytropis falcata Bunge have a positive effect on idiopathic pulmonary fibrosis by inhibiting the TGF-ß1/Smad signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with unknown etiology. Oxytropis falcata Bunge (O. falcata) is a 1-35 cm high perennial clustered herb, also known as edaxia, has viscosity and a special smell, and is mainly distributed in the western areas of China. The root of O. falcata has a diameter of 6 mm, is straight and deep, dark red and its stems are shortened, woody and multibranched. O. falcata has heat-clearing, detoxification, analgesic, anti-inflammatory, antibacterial, hemostatic and antitumor activities. Furthermore, O. falcata has excellent anti-inflammatory and analgesic effects, and it is one of the three major anti-inflammatory drugs in Tibetan medicine, known as "the king of herbs". Total flavonoids of Oxytropis falcata Bunge (FOFB) were previously extracted, and their pharmacological activities are consistent with those of the whole herb. In this study, FOFB was extracted from O. falcata by ethanol extraction, and the mechanism of FOFB on IPF was verified by in vivo and in vitro experiments. AIM OF THE STUDY: In this study, we aimed to observe the effects of FOFB on idiopathic pulmonary fibrosis. MATERIALS AND METHODS: In in vivo experiments, an IPF rat model was established by bleomycin induction. The rats were treated with FOFB (100, 200, 400 mg kg-1·d-1) for 4 weeks. Masson staining and the expression of TGF-ß, p-Smad2, p-Smad3 and Smad7 in the lung tissue of rats were detected. In in vitro experiments, we perfused normal rats with FOFB (100, 200, 400 mg kg-1·d-1) and obtained the corresponding drug-containing serum. The HFL-1 cell model induced by TGF-ß1 was used to detect the corresponding indices through intervention with drug-containing serum. The best intervention time for drug-containing serum was detected by the CCK-8 method. Changes in apoptosis, cytoskeleton and rough endoplasmic reticulum structure were detected. Finally, the expression of TGF-ß, p-Smad2, p-Smad3 and Smad7 in cells was examined. RESULTS: In vivo, Masson staining indicated that the degree of pulmonary fibrosis increased significantly, the expression of TGF-ß, p-smad2 and p-Smad3 increased significantly, and the expression of Smad7 decreased in the model group. We found that the degree of pulmonary fibrosis gradually decreased and that the inhibition of the TGF-ß/Smad signaling pathway became more obvious with increasing FOFB dose. FOFB (400 mg kg-1·d-1) significantly improved the degree of pulmonary fibrosis in rats. In in vitro experiments, the CCK-8 results showed that 120 h was the best intervention time for drug-containing serum. In the model group, there was no obvious apoptosis or changes in microfilaments and microtubules, the number of rough endoplasmic reticulum increased, and the expression of TGF-ß, p-Smad2 and p-Smad3 increased significantly, while the expression of Smad7 decreased significantly. We found that with the increase in drug-containing serum concentration, the apoptosis, cytoskeleton and degree of destruction of the rough endoplasmic reticulum in the HFL-1 cell model also increased, and the inhibition of the TGF-ß/Smad signaling pathway became more pronounced; the effect of the drug-containing serum administered with FOFB (400 mg kg-1·d-1) was the most significant. CONCLUSIONS: The results suggest that FOFB can improve the occurrence and development of IPF. The effect of FOFB on IPF may be mediated by inhibition of the TGF-ß1/Smad signaling pathway.

Effect of Total Flavonoids of Oxytropis falcata Bunge on the Expression of p-JAK1-and p-STAT1-Related Proteins in Idiopathic Pulmonary Fibrosis.

OBJECTIVE: The study aimed to explore the effect of total flavonoids of Oxytropis falcata Bunge (FOFB) on the expression of p-JAK1/p-STAT1 and SOCS3 proteins in idiopathic pulmonary fibrosis (IPF). METHODS: Rats model with IPF was established by one-off intratracheal injection of bleomycin (BLM, 5 mg/kg). After 14 days, the same volume of low dose (100 mg/kg), medium dose (200 mg/kg), and high dose (400 mg/kg) of FOFB and prednisolone acetate (20 mg/kg) as positive control drugs, as well as normal saline, were orally administered to rats once a day for 28 consecutive days. Subsequently, the degree of fibrosis and alveolitis in rat lung tissue was observed, respectively, by HE and Masson staining. Further more, observing the ultrastructure of lung tissue by transmission electron microscopy (TEM), the detection of JAK/STAT pathway related indicators including p-JAK1, p-STAT1, and SOCS3 with immunohistochemistry and SOCS3 with real-time PCR (RT-PCR) was performed. RESULTS: Compared with the BLM group, the degree of alveolitis and fibrosis improved significantly, and the expression of p-JAK1 and p-STAT1 decreased; conversely, the expression of SOCS3 increased in the treatment group. CONCLUSION: IPF causes high expression of p-JAK1 and p-STAT1 and low expression of SOCS3. FOFB can play a role in the treatment of IPF via upregulating SOCS3 and downregulating p-JAK1 and p-STAT1.

Temperature elevation and Vibrio cyclitrophicus infection reduce the diversity of haemolymph microbiome of the mussel Mytilus coruscus.

Haemolymph microbiome was considered to be unique to healthy invertebrates and beneficial to the host against external pathogens, including disease resistance and maintenance of homeostasis. Here, we investigated the effects of elevated water temperature on infection of haemolymph microbiome of the hard-shelled mussel (Mytilus coruscus). Exposure to Vibrio. cyclitrophicus resulted in high mortality of mussels on day nine at 27 °C. The haemolymph was collected to determine the microbiota by 16 S rRNA gene sequencing. Exposure to waterborne V. cyclitrophicus increased the mortality of mussels that was associated with a reduction in the diversity of their microbial community. Principal coordinate analysis (PCoA) revealed that temperature was an essential factor in shaping microbial communities in mussel haemolymph. Vibrio exposure promoted the proliferation of opportunistic pathogens (e.g., Arcobacter and Francisella) at a lower temperature. A high abundance of Vibrio present in live and dead mussels, at 27 °C might contribute greatly to mortality, as indicated by linear discriminant analysis effect size (LEfSe). These data suggested that the dynamics of microbial community have unique biomarker species in mussel haemolymph that could be used as health indicators. An elevated temperature may reduce the ability of bacterial elimination function against infection in mussel haemolymph.

Characterization of Gut Microbiome in the Mussel Mytilus galloprovincialis in Response to Thermal Stress.

The gut microbiota is essential for utilization of energy and nutrition and may have a role in host immunity in response to environmental shifts. The present study evaluated the temperature stress (increasing from 21 to 27°C) on gut microbiome and dynamics of the mussel Mytilus galloprovincialis by 16S rRNA gene sequencing with the aim of discovering the gut microbiome resilience to warming. Exposure to high temperature of 27°C significantly reduced the survival of M. galloprovincialis associated with increased microbial diversity of gut. The microbial communities were shifted with elevated temperature (from 21 to 27°C) and different exposure time (from day 0 to day 7) by principal coordinate analysis (PCoA). Linear discriminant analysis effect size (LEfSe) revealed that the relative abundance of Vibrio and Arcobacter presented in live animals as the top genus-level biomarkers during the initial exposure to 27°C and followed by microbiomes fluctuation with increasing exposure time at day 4 and day 7. The proliferation of opportunistic pathogens such as genus Vibrio and Arcobacter might increase host susceptibility to disease and contributed greatly to mortality. The results obtained in this study provide the knowledge on ecological adaptation for south domestication of M. galloprovincialis and host-bacteria interaction during temperature stress (27°C).

Blood-typing and irregular antibody screening through multi-channel microfluidic discs with surface antifouling modification.

A novel surface modification technology for microfluidic disks was developed for multichannel blood-typing detection and irregular antibody screening. The antifouling material, poly(ethylene glycol) methacrylate (PEGMA), was used to modify the surface of the microfluidic disk for improving its hydrophilicity and blood compatibility. With the modification of PEGMA, the hydrophilicity was sufficiently improved with a 44.5% reduction of water contact angle. The modified microfluidic disk also showed good biocompatibility with a reduction of hemolytic index (from 3.4% to 1.2%) and platelet adhesion (from 4.6 × 104/cm2 to 1.9 × 104/cm2). Furthermore, the PEGMA modification technique conducted on the microfluidic disk achieved successful adjustment of burst frequency for each chamber in the microchannel, allowing a sequential addiction of reagents in the test protocol of manual polybrene (MP) blood typing. Clinical studies showed that the proposed MP microfluidic disk method not only performed at extremely high consistency with the traditional tube method in the identification of ABO/RhD blood types, but also accomplished an effective screening method for detecting irregular antibodies. In conclusion, this study demonstrated that the easily mass-produced MP microfluidic disk exhibited good blood-typing sensitivity and was suitable for clinical applications.

Two toll-like receptors identified in the mantle of Mytilus coruscus are abundant in haemocytes.

Toll-like receptors (TLRs) are a large family of pattern recognition receptors (PRRs) that play a critical role in innate immunity. TLRs are activated when they recognize microbial associated molecular patterns (MAMPs) of bacteria, viruses, or fungus. In the present study, two TLRs were isolated from the mantle of the hard-shelled mussel (Mytilus coruscus) and designated McTLR2 and McTLR3 based on their sequence similarity and phylogenetic clustering with Crassostrea gigas, CgiTLR2 and CgiTLR3, respectively. Quantitative RT-PCR analysis demonstrated that McTLR2 and McTLR3 were constitutively expressed in many tissues but at low abundance.

Home-based cardiac rehabilitation improves quality of life, aerobic capacity, and readmission rates in patients with chronic heart failure.

BACKGROUND: Exercise tolerance and cardiac output have a major impact on the quality of life (QOL) of patients experiencing heart failure (HF). Home-based cardiac rehabilitation can significantly improve not only exercise tolerance but also peak oxygen uptake ((Equation is included in full-text article.)peak), and the QOL in patients with HF. The aim of this prospective study was to evaluate the beneficial effects of home-based cardiac rehabilitation on the quality of medical care in patients with chronic HF. METHODS: This study was a randomized prospective trial. HF patients with a left ventricular ejection fraction (LVEF) of less than 50% were included in this study. We randomly assigned patients to the control group (n = 18) and the interventional group (n = 19). Within the interventional group, we arranged individualized rehabilitation programs, including home-based cardiac rehabilitation, diet education, and management of daily activity over a 3-month period. Information such as general data, laboratory data, Cardiopulmonary Exercise Test (CPET) results, Six-minute Walk Test (6MWT) results, and the scores for the Minnesota Living with Heart Failure Questionnaire (MLHFQ) before and after the intervention, was collected from all patients in this study. RESULTS: Patients enrolled in the home-based cardiac rehabilitation programs displayed statistically significant improvement in (Equation is included in full-text article.)peak (18.2 ±â€Š4.1 vs 20.9 ±â€Š6.6 mL/kg/min, P = .02), maximal 6-Minute Walking Distance (6MWD) (421 ±â€Š90 vs 462 ±â€Š74 m, P = .03), anaerobic threshold (12.4 ±â€Š2.5 vs 13.4 ±â€Š2.6 mL/kg/min, P = .005), and QOL. In summary, patients receiving home-based cardiac rehabilitation experienced a 14.2% increase in (Equation is included in full-text article.)peak, a 37% increase in QOL score, and an improvement of 41 m on the 6MWD test. The 90-day readmission rate for patients reduced to 5% from 14% after receiving cardiac rehabilitation. CONCLUSION: Home-based cardiac rehabilitation offered the most improved results in functional capacity, QOL, and a reduced the rate of readmission within 90 days.

Is thyroid status associated with cognitive impairment in elderly patients in China?

BACKGROUND: The relationship between alterations in thyroid function and cognitive deficits has been investigated in several previous studies. Hypo-or hyperthyroidism and, to a lesser extent, subclinical thyroid dysfunction can negatively affect cognitive performance. However, limited data are available on the potential association of thyroid function with mild cognitive impairment (MCI) and Alzheimer's disease (AD) in the elderly Chinese population. METHODS: In the present study focusing on a population of elderly Chinese individuals ≥ 50 years of age, 77 cognitively normal controls, 64 patients with MCI, and 154 patients diagnosed with AD underwent assessment of thyroid status using thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) levels as variables. Cognitive function was evaluated with the aid of comprehensive neuropsychological tests, such as the Mini-Mental State Examination (MMSE) and Memory and Executive Screening (MES). RESULTS: Overall, 88.1 % of the subjects displayed normal thyroid function, 4.7 % were diagnosed with clinical hypothyroidism, 3.1 % with subclinical hypothyroidism, and 4.1 % with subclinical hyperthyroidism. After adjusting for covariates (age, sex, education years and body mass index), no association was evident between mild cognitive impairment or AD and thyroid dysfunction. However, lower serum TSH was correlated with risk of AD (odds ratio [OR]: 2.78, 95 % confidence interval [95% CI]: 1.11-6.99). CONCLUSION: Neither hypothyroidism nor subclinical hyperthyroidism was associated with AD and MCI in this population-based elderly Chinese cohort. Our findings need to be confirmed in a longitudinal study.

[Effects of Banxia Xiexin Decoction Containing Serum on Proliferation, Invasion and Metastasis of Gastric Cancer Peritoneal Metastasis Cell Line GC9811-P].

Objective To observe the effects of Banxia Xiexin Decoction (BXD) containing ser- um on proliferation, invasion and metastasis of in vitro human gastric cancer peritoneum cell strain GC9811-P (which has high metastatic potential). Methods BXD containing serum was prepared. GC9811-P cells were inoculated in the E-Plate 96 and CIM Plate 16, and then 0, 25, 50, 100 µL/mL BXD containing serums were added respectively. Meanwhile, GC9811-P cells were stained by Diff-Quik stai- ning method. Inhibition of BXD containing serum on cell index (CI) for proliferation of GC9811-P cells, invasion and metastasis were observed by real time cellular analysis (RTCA) and Diff-Quik staining method. Results BXD containing serum could obviously inhibit the proliferation of GC9811-P cells. The Cl approximated to 0 after 70 h. Most stained Diff-Quik cells died. Cell migration curve showed that 25, 50, 100 µL/mL BXD containing serums could obviously inhibit the capacities for cell migration of GC9811-P cells in concentration dependent manner. The number of migration cells was reduced more obviously, as com- pared with 0 µL/mL BXD containing serum (P <0. 05). Conclusion BXD containing serums could inhibit the proliferation, invasion and metastasis of GC9811-P cells, which might be associated with blocking peritoneal metastasis of gastric cancer.

Influence of ß-blockers on heart rate recovery and rating of perceived exertion when determining training intensity for cardiac rehabilitation.

BACKGROUND: The influence of ß-blockers on heart rate recovery (HRR) and rating of perceived exertion (RPE) during Phase I cardiac rehabilitation (CR) for patients with a recent episode of acute myocardial infarction (AMI) is not clear. METHODS: From October 2009 to July 2011, 105 patients with a recent episode of AMI who received a successful percutaneous coronary intervention were recruited into this study. Before entering Phase II CR, each patient underwent a cardiopulmonary exercise test (CPET), where RPE was assessed every minute and related parameters were recorded. RESULTS: The participants entering CR had relatively low mean peak oxygen consumption (VO2max). However, the peak heart rate and VO2max were lower in those taking ß-blockers. The RPE value at the ventilatory threshold (VT) was significantly higher (12.7 ± 1.7) in participants who were taking ß-blockers relative to those who were not (11.5 ± 1.4). The HRR value was lower (12.5 ± 8.8) in participants who were taking ß-blockers relative to those who were not (17.0 ± 9.1). CONCLUSION: These findings suggest that use of ß-blockers increased the RPE value at the VT. In addition, HRR was attenuated by ß-blockers. In patients who do not undergo CPET, the use of ß-blockers should be taken into consideration when using RPE for the initial exercise prescription to determine training intensity.

Adjustable bioadhesive control of PEGylated hyperbranch brushes on polystyrene microplate interface for the improved sensitivity of human blood typing.

A PEGylated 96-well polystyrene (PS) microplate was first introduced for applications in high-throughput screening for selective blood typing to minimize the risks in blood transfusions. Herein, we present a hemocompatible PS 96-well microplate with adjustable PEGylated hyperbranch brush coverage prepared by ozone pretreated activation and thermally induced surface PEGylation. The grafting properties, hydration capacity, and blood compatibility of the PEGylated hyperbrush immobilized PS surfaces in human blood were illustrated by the combined chemical and physical properties of the surface, and the dependence of the specific absorption of human plasma fibrinogen onto the PEGylated surfaces on the grafting density was analyzed by monoclonal antibodies. The surface coverage of PEGylated brushes plays a major role in the bioadhesive properties of modified PS microplates, which in turn control the level of agglutination sensitivity in blood typing. The bioadhesive resistance toward proteins, platelets, and erythrocytes in human whole blood showed a correlation to the controlled hydration properties of the PEGylated hyperbrush-modified surfaces. Therefore, we suggested that the surface coverage of PEGylated hyperbrushes on PS surfaces can increase the sensitivity of cross-matching blood agglutination by up to 16-fold compared to that of the conventional 96-well virgin PS due to the regulated biorecognition of hematocrit and antibodies of the PEGylated hyperbrush-modified surfaces.

[The characteristics and clinical manifestation of subjects with non-specific pattern of pulmonary function tests].

OBJECTIVE: To analyze the characteristics of pulmonary function and the clinical significance of non-specific pattern (NSP). METHODS: A total of 1933 pulmonary function tests of adult patients were analyzed, and those with NSP were selected. The pulmonary function test results, clinical diagnosis and radiological manifestations were analyzed. Normal distribution data were compared by t test, while non-normal distribution data were compared by Mann-Whitney U test, and χ(2) test was used to compare ratios. RESULTS: There were 61 patients in the NSP group and 1017 in the control group. The BMI of the 2 groups was (24.5 ± 4.6) and (24.5 ± 3.8) kg/m(2), respectively, being not significantly different (t = 0.008, P > 0.05). The age was 64 (49-74) years and 56 (42-70) years, and the smoking index was 0.4 (0-20) and 0 (0-10), respectively, showing no significant differences (Z values were -2.209 and -2.571, respectively, all P < 0.05). In the NSP group, FEV1 was 69% (66%-73%) predicted, FVC 75% (70%-77%) predicted, FEV1/FVC 75% (73%-78%), RV 118% (105%-145%) predicted, and TLC 86% (82%- 93%) predicted, which were significantly different as compared to those of the control group [95% (87%-104%), 98% (90%-106%), 79% (76%-84%), 101% (88%-114%) and 94% (88%-102%), respectively],(Z values are -13.059--5.185, all P < 0.05). RV/TLC was (52 ± 11)% in the NSP group and (39 ± 9)% in the control group, the difference being significant (t = -10.351, P < 0.05). The decreased TLC indicated restricted ventilation, while the increased RV and RV/TLC indicated air trapping. The clinical diagnosis of NSP included obstructive and restrictive diseases, some of which showed severe radiological abnormalities, but there were 31 patients without pulmonary lesions. CONCLUSIONS: Age and smoking, but not obesity, may play a role in NSP.NSP has characteristics of obstructive and restrictive ventilation defects, but does not associate with particular diseases, thus having limited clinical significance.

A NMR-based metabolomic approach for differentiation of hagfish dental and somatic skeletal muscles.

The hagfish dental muscle is a large and specialized element of the feeding apparatus that helps ingest food. This muscle has enzymatic activities and contractile properties different from the hagfish somatic skeletal muscle. To verify the functional relevance of protein alterations, we examined the metabolomic differentiation of hagfish dental and somatic skeletal muscles using ¹H-nuclear magnetic resonance (NMR)-based metabolomics and multivariate analysis that separated hagfish dental and somatic muscles by principal component analysis and partial least squares for discriminant analysis. Our analysis of assigned metabolites showed that anserine and taurine levels were higher in dental muscle, but creatine, fructose, glucose, glycerate, pyruvate, and succinate levels were higher in somatic muscle. We concluded that the primary energy sources of dental and somatic muscles are related to the citric acid cycle and the anaerobic glycolysis and metabolism of creatine. Thus, ¹H-NMR-based metabolomics can be integrated with the previous proteomic approach to derive biochemical and physiological information about hagfish muscles.