AbstractPurpose: This study aimed to explore the regulation and mechanism of Cathepsin K (CTSK) in bone invasive pituitary adenomas (BIPAs). Experimental Design: A total of 1437 patients with pituitary adenomas were included and followed up. RNA sequencing, immunohistochemistry, and RT-PCR were used to analyze to detect CTSK expression. The impact of CTSK on cellular proliferation, bone matrix degradation, and osteoclasts differentiation was determined by gain/loss of function experiments in vitro and vivo. The exploration of signaling pathway was determined by molecular biology experiments. Results: Here, we reported a significant fraction (~10%) of pituitary adenoma patients developed bone invasion. Bone invasion was correleted with tumor recurrence. Shorter recurrence free survival was found in BIPA patients. CTSK expression was increased in BIPA patients and strongly associated with worse prognosis. Increased CTSK expression promoted pituitary adenoma cell proliferation via activation of mammalian target of rapamycin (mTOR) signaling pathway and bone invasion via increasing osteoclast differentiation in vitro and in vivo. CTSK inhibitor (odanacatib) could inhibit pituitary adenoma cell proliferation and bone invasion in vitro and in vivo. CTSK promoted osteoclast differentiation by promoting the RANKL expression of MC3T3-E1 cells through interaction with TLR4. Conclusion: CTSK may become a novel predictive biomarker and potential therapeutic target for BIPAs.
Abstract Background Mycoplasma conjunctivae ( M. conjunctivae ) belongs to the Mycoplasma species of the Mycoplasma family and it is the main pathogen that causes infectious keratoconjunctivitis in goats. Infectious keratoconjunctivitis (IKC), also known as red eye disease, is a highly contagious disease that is prevalent worldwide. Case presentation: In October 2022, a goat farm in Tongxin County, Ningxia Hui Autonomous Region, China began to show leukoplakia in the eyes of goats 3 days later due to the introduction of a batch of goats and no isolation observation. The diseased goat showed listlessness and poor appetite. Its body temperature was as high as 41°C. The eyes began to appear white spots, and its range gradually expanded, covering the entire eyeball. 200 goats were purchased, 40 goats were affected, the incidence rate was 20%. Eye secretions of 15 diseased goats were collected and were amplified by using specific primers. The amplified products were sequenced and phylogenetic trees were constructed. The phylogenetic tree showed that Mco 01, Mco 02, Mco 03, Mco 04, Mco 05, Mco 06, Mco 07, Mco 08, Mco 09, Mco 10, Mco 11, Mco 12, Mco 13, Mco 14 and Mco 15 had the closest genetic distance with the reported M.conjunctivae Goat 655 and M165 / 69 strains, and the self-test support rate with Goat 655 was as high as 98. Conclusions This study is the first to identify M.conjunctivae from the eye secretions of goats with IKC in goats from Ningxia Hui Autonomous Region. Under the stress conditions of long-distance transportation, the health status of goats should be highly concerned, and timely prevention of M. conjunctivae disease can improve the survival rate of purchased goats.
Hepatitis B virus (HBV) is a hepatotropic DNA virus and its infection results in acute or chronic hepatitis.It is reported that the host innate immune system contributes to viral control and liver pathology, while whether and how HBV can trigger the components of innate immunity remains controversial.In recent years, the data accumulated from HBV-infected patients, cellular and animal models have challenged the concept of a stealth virus for HBV infection.This editorial focuses on the current findings about the innate immune recognition to HBV.Such evaluation could help us to understand HBV immunopathogenesis and develop novel immune therapeutic strategies to combat HBV infection.
Abstract Background In recent years, the prevalence of hand, foot, and mouth disease (HFMD) caused by enteroviruses other than enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) has gradually increased. The pathogen spectrum of HFMD also continues to change. In this study, we analyzed the epidemiological characteristics of HFMD and the genetic characteristics of the coxsackievirus A10 (CVA10) virus identified in Taiyuan City, Shanxi Province. Methods The epidemiological data from 2016–2020 on HFMD in Taiyuan City was collected from the China Information System For Disease Control and Prevention. The throat swab specimens of 2701 HFMD cases were tested, theVP1regions of CVA10 RNA were amplified using RT-PCR, and phylogenetic analysis of CVA10 was performed. The study results were analyzed using Pearson's Chi-Square Test. Results Children aged 1–5 years accounted for the majority (81.65%) of all HFMD cases, and the average annual incidence is higher in boys than in girls. Of the 2,701 specimens collected, 1,439 (53.28%) were positive for human enterovirus (EV). The positivity rates of EV-A71, CVA16, and other EVs were 15.22% (219/1439), 28.77% (414/1439), and 56.01% (806/1439), respectively. The proportion of specimens positive for other EVs was significantly higher than that of EV-A71 and CVA16. CVA10 is one of the important viruses of other EVs. A total of 52 CVA10 strains were used for phylogenetic analysis based on theVP1region. Of the 52 CVA10 strains, 31 were from this study, and 21 were downloaded from GenBank. All CVA10 sequences could be assigned to seven genotypes (A, B, C, D, E, F, and G), and genotype C was further divided into C1 and C2 subtypes. Of the 31 CVA10 strains identified in this study, only one belonged to subtype C1 and the remaining 30 belonged to C2. Conclusions This study emphasized the importance of strengthening the surveillance of the HFMD in order to understand the mechanisms of pathogen variation and evolution, so as to provide a scientific basis for HFMD prevention, control, and vaccine development.
Background: Patients with diabetes and co-existing chronic kidney disease and/or cardiovascular disease have complex medical needs with multiple indications for different guideline-directed medical therapies and require high health care resource utilization. The Cardiac and Renal Endocrine Clinic (C.a.R.E. Clinic) is a multi- and interdisciplinary clinic offering a unique care model to this population to overcome barriers to optimal care. Objective: To describe the patient characteristics and clinical data of consecutive patients seen in the C.a.R.E. Clinic between 2014 and 2020, with a focus on the feasibility, strengths, and challenges of this outpatient care model. Design: Single-center retrospective cohort study. Setting: The C.a.R.E. Clinic is a multi- and interdisciplinary clinic at Toronto General Hospital in Toronto, Canada. Patients: We reviewed the charts of all 118 patients who had been referred to the C.a.R.E. Clinic with type 2 diabetes mellitus, co-existing renal disease, and/or cardiovascular disease. Measurements: Demographic data, medication data, clinic blood pressure measurements, and laboratory data were assessed at the first and last available clinic visit. Methods: Data were extracted via manual chart review of paper and electronic medical records. Results: First and last attended clinic visit data were available for descriptive analysis in 74 patients. There was a significant improvement in low-density lipoprotein (LDL) cholesterol (1.9 mmol/L vs 1.5 mmol/L, P < .01), hemoglobin A1C (7.5% vs 7.1%, P = .02), and the proportion of patients with blood pressure at target (52.7% vs 36.5%, P = .04), but not body mass index (29.7 kg/m² vs 29.6 kg/m², P = .15) between the last and first available clinic visits. There was higher uptake in evidence-based medication use including statins (93.2% vs 81.1%, P = .01), SGLT-2i (35.1% vs 4.1%, P < .01), and GLP-1 receptor agonists (13.5% vs 4.1%, P = .02), while RAAS inhibitor use was already high at baseline (81.8% vs 78.4%, P = .56). There remains a significant opportunity for therapy with sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Limitations: This is a retrospective chart review lacking a control group, therefore clinical improvements cannot be causally attributed to the clinic alone. New evidence and changes to guideline-recommended therapies also contributed to practice changes during this time period. Conclusions: A multi- and interdisciplinary clinic is a feasible and potentially effective way to improve evidence-based and patient-centered care for patients with diabetes, kidney, and cardiovascular disease.
Objective
To assess the efficacy and safety of nebulized hypertonic saline solution in infant with bronchiolitis.
Methods
From January 2014 to January 2016, 95 patients at 3-13 months old in our hospital who diagnosed as bronchiolitis were randomly divided into three groups.On the basis of conventional suit support treatment, the observation group A was given nebulized 3% hypertonic saline (n=32), the observation group B was given nebulized 3% hypertonic saline and salbutamol (n=32), and the control group C was given nebulized normal saline(0.9%) and salbutamol (n=31), this therapy was repeated every 6 hours until discharge.The Lowell score, clinical symptoms remission time, days of hospitalization and incidence rate of adverse reaction of the three groups were compared.
Results
After treatment, the symptoms and signs of the three groups were all improved.The Lowell scores were lower in the two observation groups compared to the control group C in 24, 48, 72 hours after treatment[(5.81±1.53)points and (5.85±1.37) points vs.(6.61±1.54) points, (4.75±1.34) points and (4.72±1.30) points vs.(5.52±1.29) points, (3.19±1.15) points and (3.22±1.16) points vs.(3.90±1.01) points, Z=-1.999, -2.241, -2.518 and -2.002, -2.335, -2.316, all P 0.05]. Children in three groups had no serious adverse events (all P>0.05).
Conclusion
Nebulized hypertonic saline in the treatment of bronchiolitis can relieve symptoms and signs, shorten the hospitalization time, and has less adverse reaction, it is worthy of clinical use.
Key words:
Bronchiolitis; Sodium chloride; Nebulize
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