Adjusted Global Antiphospholipid Syndrome Score (aGAPSS) and PLT, APTT: Predictive Value of Thrombotic Risk Assessment in SLE Patients.

BACKGROUND: Risk assessment of vascular thrombosis in SLE patients with the presence of antiphospholipid antibodies (aPL) remains a challenge. The adjusted global antiphospholipid syndrome score (aGAPSS) has been validated and used to predict aPL-related thrombosis in SLE patients in some countries. Relevant data of aGAPSS in thrombotic evaluation in SLE population from China has not been reported. We aim to validate aGAPSS in thrombosis assessment in Chinese patients with SLE and to explore the correlations of aGAPSS with routine laboratory parameters and their clinical significance as well. METHODS: A total of 166 consecutive SLE patients were retrospectively analyzed. Multivariate logistic regression analysis was performed to examine the impact of multiple cardiovascular risk factors and laboratory parameters in recurrent thrombosis risk in SLE. ROC was conducted to explore the discriminative ability of aGAPSS and platelet (PLT), activated partial thromboplastin time (APTT), alone or in combination. RESULTS: Significantly higher value of aGAPSS was seen in SLE patients with vascular thrombosis. ROC curve indicated that aGAPSS of 3.5 or more had the best diagnostic accuracy for the prediction of aPL-related thrombosis in SLE patients. PLT with cutoff of 187.5 x 109/L and APTT with 37.5 seconds were predictors of aPL-related thrombosis as well. The combination of aGAPSS with PLT and APTT improved AUC compared to aGAPSS alone. CONCLUSIONS: The aGAPSS could predict the risk of aPL-related vascular thrombosis in SLE patients from China. The combination of aGAPSS with PLT and APTT was first time proved to have better predictive performance in thrombosis risk assessment in SLE.

The hydroxamic acid derivative YPX-C-05 alleviates hypertension and vascular dysfunction through the PI3K/Akt/eNOS pathway.

BACKGROUND: Hypertension is a prevalent cardiovascular disease characterized by elevated blood pressure and increased vascular resistance. HDAC inhibitors have emerged as potential therapeutic agents due to their ability to modulate gene expression and cellular processes. YPX-C-05, a novel hydroxamic acid-based HDAC inhibitor, shows promise in its vasodilatory effects and potential targets for hypertension treatment. In this study, we aimed to elucidate the mechanisms underlying YPX-C-05's vasodilatory effects and explore its therapeutic potential in hypertension. METHODS: To determine the ex vivo vasodilatory effects of YPX-C-05, isolated aortic rings precontracted with phenylephrine were used. We assessed YPX-C-05's inhibitory effects on HDACs and its impact on histone H4 deacetylation levels in endothelial cells. Network pharmacology analysis was employed to predict putative targets of YPX-C-05 for hypertension treatment. To investigate the involvement of the PI3K/Akt/eNOS pathway, we employed enzyme-linked immunosorbent assay and to assess the levels of NO, ET-1, BH2, and BH4 in human umbilical vein endothelial cells. And we also analyzed the mRNA expression of eNOS and ET-1. Furthermore, Western blotting was conducted to quantify the phosphorylated and total Akt and eNOS levels in human umbilical vein endothelial cell lysates following treatment with YPX-C-05. In order to elucidate the vasodilatory mechanism of YPX-C-05, we employed pharmacological inhibitors for evaluation purposes. Furthermore, we evaluated the chronic antihypertensive effects of YPX-C-05 on N-omega-nitro-L-arginine-induced hypertensive mice in an in vivo model. Vascular remodeling was assessed through histological analysis. RESULTS: Our findings demonstrated that YPX-C-05 exerts significant vasodilatory effects in isolated aortic rings precontracted with phenylephrine. Furthermore, YPX-C-05 exhibited inhibitory effects on HDACs and increased histone H4 acetylation in endothelial cells. Network pharmacology analysis predicted YPX-C-05 might activate endothelial eNOS via PI3K/Akt signaling pathway. Inhibition of the PI3K/Akt/eNOS pathway attenuated the vasodilatory effects of YPX-C-05, as evidenced by reduced levels of phosphorylated Akt and eNOS in human umbilical vein endothelial cell lysates. The chronic administration of YPX-C-05 in N-omega-nitro-L-arginine-induced hypertensive mice resulted in significant antihypertensive effects. Histological analysis demonstrated a reduction in vascular remodeling, further supporting the therapeutic potential of YPX-C-05 in hypertension. CONCLUSION: This study demonstrates for the first time that the novel hydroxamic acid-based HDAC inhibitor YPX-C-05 produces significant antihypertensive and vasodilatory effects through the PI3K/Akt/eNOS pathway. Our findings support the developing prospect of YPX-C-05 as a novel antihypertensive drug.

Multiple metastases of clear cell sarcoma at diagnosis presented in bone marrow aspirate: A case report.

Clear cell sarcoma (CCS) is a rare and aggressive soft-tissue sarcoma that arises most commonly in adolescents and young adults of both sexes. CCS presents a diagnostic challenge due to its morphological and immunohistochemical similarity to malignant melanoma. We present a rare and severe case of CCS simultaneously with multiple bone and lymph node metastases at the time of initial diagnosis in a previously healthy 15-year-old Chinese man. Detailed information on clinical manifestations, laboratory profiles, histopathological findings and poor outcome were described. The cytomorphology of bone marrow aspirate in CCS in Wright-Giemsa staining smear was first depicted in this case. The diagnostic difficulties of the rare case was also discussed.

Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation.

The existence of latent viral reservoirs (LVRs), also called latent cells, has long been an acknowledged stubborn hurdle for effective treatment of HIV-1/AIDS. This stable and heterogeneous reservoir, which mainly exists in resting memory CD4+ T cells, is not only resistant to highly active antiretroviral therapy (HAART) but cannot be detected by the immune system, leading to rapid drug resistance and viral rebound once antiviral treatment is interrupted. Accordingly, various functional cure strategies have been proposed to combat this barrier, among which one of the widely accepted and utilized protocols is the so-called 'shock-and-kill' regimen. The protocol begins with latency-reversing agents (LRAs), either alone or in combination, to reactivate the latent HIV-1 proviruses, then eliminates them by viral cytopathic mechanisms (e.g., currently available antiviral drugs) or by the immune killing function of the immune system (e.g., NK and CD8+ T cells). In this review, we focuse on the currently explored small molecular LRAs, with emphasis on their mechanism-directed drug targets, binding modes and structure-relationship activity (SAR) profiles, aiming to provide safer and more effective remedies for treating HIV-1 infection.

Cryptococcal Meningitis in a Patient with Sjogren's Syndrome: a Case Report.

BACKGROUND: Cryptococcal meningitis (CM) is a life-threatening infectious disease and causes high morbidity and mortality. No information about Cryptococcal meningitis in populations with Sjogren's syndrome (SS) was available. METHODS: This report details the first case of Cryptococcal meningitis in a 75-year-old female patient with 10-years history of Sjogren's syndrome. RESULTS: Detailed findings of C. neoformans from CSF examinations, including routine examination, India ink stain, immunological test, culturing, mass spectrum analysis and molecular biology identification were all delineated in this case, which facilitated understanding of detection methods in C. neoformans infection. The etiological exploration was initiated from a positive finding of yeast cells in routine examination of unstained CSF in the present case. Morphology description of C. neoformans in unstained CSF was depicted for the first time. CONCLUSIONS: Clinicians should consider the possible complication of Cryptococcal meningitis when patients with Sjogren's syndrome show neurological symptoms. Importance of screening yeast cells from unstained CSF for routine examination was emphasized, which may reduce errors in cell counting and trigger further etiological ex-ploration of C. neoformans infection in laboratory and clinical practice.

Evaluation of efficacy and safety of propofol in the treatment of procedural sedation/anesthesia in neonates: A protocol for systematic review and meta-analysis.

BACKGROUND: In newborns, propofol anesthesia is commonly utilized. Propofol is increasingly being shown to be effective and safe in treating procedural sedation and anesthesia in neonates. This research aims to evaluate the efficacy and safety of propofol in neonates using systematic review and meta-analysis methodologies. METHODS: A thorough review and meta-analysis of studies on propofol anesthesia in neonates will be conducted. Conduct comprehensive searches in Web of Science, PubMed, Cochrane Library, EMBASE database, WanFang database, and Chinese biomedical literature database before May 25, 2021, to obtain published and qualified research. Two reviewers will assess the quality of the included papers and extract the data independently. Then, for meta-analysis, we will utilize RevMan 5.3 software. RESULTS: This study will pool the data of separate trials to analyze the efficacy and safety of propofol in the treatment of procedural sedation/anesthesia in neonates. CONCLUSION: Our findings will give strong data for determining whether propofol is an effective treatment for procedural anesthesia in neonates.

Strongyloides stercoralis Infection in a Patient with Chronic Renal Failure from North China.

INTRODUCTION: Human strongyloidiasis is a generally neglected parasitic disease of major global distribution, spreading commonly in tropical and subtropical areas. As for China, strongyloidiasis occur mainly in South of China and no relevant information about the parasite infection in North China was available. CASE PRESENTATION: An 84-year-old man from Shanxi province, North China, was admitted to Department of Nephrology with complaints of a 7-month history of intermittent edema of both lower extremity with foam urine and 3-day history of fever, chill and diarrhea. Large numbers of rhabditiform larva of Strongyloides stercoralis (S. stercoralis) were observed in a stool sample. Diagnosis of S. stercoralis infection was established by morphological observations of larvae under the microscope in both wet mount and Wright-Giemsa staining smear and further confirmed by molecular biology identification. CONCLUSIONS: We report a rare case of S. stercoralis infection in a patient with chronic renal failure from North China, which implies the possibility of developing human strongyloidiasis in cooler climates. In addition, our case suggests that clinicians should consider the complication of S. stercoralis infection in immunosuppressed patient populations with chronic renal failure. Morphological details of S. stercoralis in Wright-Giemsa staining was first described in the present case. Our results also support the use of molecular techniques targeting COX1 gene sequence for the diagnosis of S. stercoralis infection, which was prove to be necessary in laboratory practice, especially for those inexperienced morphologists in temperature zone.

A 49-Year-Old Man Presents With Fever of Unknown Origin and Cough.

CASE PRESENTATION: A 49-year-old man presented with 3 months of persistent fever, cough, shortness of breath, and chest tightness. He had no response to treatment with antibiotics. He had been treated with an empiric 2-week course of steroids approximately 2 months before presentation, with mild and transient improvement. He did not use tobacco and had not experienced any weight loss, hemoptysis, arthralgia, or myalgia, and was otherwise in good health. He denied contact with anyone with pulmonary TB or other respiratory illnesses.

Confirmed Cryoglobulinemia and Hyperviscosity Syndrome Secondary to Multiple Myeloma-IgA Kappa from Routine Blood Test: a Case Report.

BACKGROUND: Cryoglobulins and hyperviscosity syndrome (HS) sometimes occur in multiple myeloma (MM), which are considered clinical emergencies. In laboratory practice, aspiration failure in routine blood tests sometimes occurs when the sample is inadequate. Here, a case of cryoglobulinemia and HS associated with advanced multiple myeloma was reported, which unusually is initially confirmed by aspiration failure in a routine blood test with sufficient sample. METHODS: A case of a 48-year-old female whose diagnosis of cryoglobulinemia and hyperviscosity syndrome secondary to MM-IgA kappa was confirmed from routine blood test. RESULTS: The sufficient sample for routine blood test could not be analyzed in a hematology analyzer due to aspiration failure, which was found to be caused by high viscosity and poor liquidity. A peripheral blood smear showed numerous non-cellular clouds, erythrocyte rouleaux formation, and plasma cell infiltration. After a water bath, the non-cellular clouds evidently disappeared, and the routine blood test was successfully conducted. Centrifugation of the sample for biochemical test, which had previously failed, was also possible. The case was confirmed as complications of cryoglobulinemia and HS associated with advanced MM, and the non-cellular clouds were identified as cryoglobulins. CONCLUSIONS: This case report provides an effective way for clinicians to deal with this kind of abnormal sample and limited but important laboratory evidence to establish early diagnosis of cryoglobulinemia and HS secondary to MM.

Dysentery Caused by Balantidium coli in China.

Balantidium coli human infection predominantly occurs in tropical and subtropical regions in the world. Human case is extremely rare in China. This report details a case of B. coli infection in a 68-year-old man in China, who presented with history of abdominal pain, tenesmus, diarrhea with blood and was diagnosed as B. coli-caused dysentery. Our case indicates possible occurrence of Balantidium coli-related disease in cooler climates. This case is presented not only because of its rarity but also for future references.

Anesthetic management of a patient with an unusual broken tracheostomy tube: a case report.

OBJECTIVE: This study was performed to investigate the management of general anesthesia in an unusual case involving a patient with a broken tracheostomy tube presenting as an airway foreign body. METHODS: We herein describe the anesthetic management of a patient with a broken tracheostomy tube. A 77-year-old Chinese man who had been involved in a car accident underwent a tracheostomy. One year later, he presented with cough and bleeding at the tracheostomy site. Preoperative evaluation revealed that the metal tracheostomy tube was lodged in his left main bronchus. General anesthesia was induced to maintain spontaneous breathing, and adequate topical anesthesia of the airway was administered. RESULTS: The metal tracheostomy tube was successful removed, and a new tracheal tube was put in place. CONCLUSIONS: General anesthesia to maintain spontaneous breathing and adequate topical anesthesia of the airway can be safely used when removing broken tracheostomy tubes.

Dexmedetomidine mitigates sevoflurane-induced cell cycle arrest in hippocampus.

BACKGROUND: Epidemiologic studies suggest the possibility of a modestly elevated risk of adverse neurodevelopmental outcomes in children exposed to anesthesia during early childhood. Sevoflurane is widely used in pediatric anesthetic practice because of its rapid induction and lower pungency. However, it is reported that sevoflurane leads to the long-term cognitive impairment. Some evidence revealed that the selective α2-adrenoreceptor agonist dexmedetomidine (DEX) exerts neuroprotective effects in various brain injury models of animals. But the role of DEX on sevoflurane-induced neuro-damage remains elusive. MATERIALS AND METHODS: In our study, we isolated the hippocampal neuron cells from newborn neonatal rats and verified the purity of neurons by immunocytochemistry. We employed the flow cytometry and western blot to examine the effect of sevoflurane, DEX and α2-adrenergic receptor antagonist yohimbine on cell cycle distribution. RESULTS: Immunocytochemistry results showed the purity of neurons > 94%, which provided a good model for neural pharmacology experiments. The exposure of sevoflurane-induced cell cycle arrest at S phase and suppressed the expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB). The addition of DEX suppressed sevoflurane-induced cell cycle arrest and the inhibitory of BDNF and TrkB expression. But the function of DEX was partly blocked by a α2 adrenergic receptor blocker yohimbine. CONCLUSION: Sevoflurane suppressed neuron cell proliferation via inhibiting the expression of BDNF and TrkB, and DEX relieved the neurotoxicity induced by sevoflurane via α2 adrenergic receptor. These findings provided new evidence that DEX exerted as a neuroprotective strategy in sevoflurane-induced neuro-damage, and provided new basis for the clinical application of DEX.

Monoclonal antibody-based colloid gold immunochromatographic strip for the rapid detection of Tomato zonate spot tospovirus.

BACKGROUND: Tomato zonate spot virus (TZSV), a new species of genus Tospovirus, caused significant losses in yield and problems in quality of many important vegetables and ornamentals in Southwest China and posed a serious threat to important economic crops for the local farmers. A convenient and reliable method was urgently needed for rapid detection and surveillance of TZSV. METHODS: The nucleocapsid protein (N) of TZSV was expressed in Escherichia coli and purified, and was used as the antigen to immunize BALB/c mice. Three monoclonal antibodies (mAbs) 3A2, 5D2 and 5F7 against TZSV were obtained through the hybridoma technique. The mAb 3A2 was conjugated with colloid gold as detecting reagent; mAb 5D2 was coated on a porous nitrocellulose membrane as the detection line and protein A was coated as the control line respectively. The colloid gold immunochromatographic (GICA) strip was assembled. RESULTS: The analysis of Dot-ELISA and Western blot showed that the obtained three independent lines of mAbs 3A2, 5D2 and 5F7 specifically recognized TZSV N. Based on the assembly of GICA strip, the detection of TZSV was achieved by loading the infected sap onto the test strip for visual inspection. The analysis could be completed within 5-10 min. No cross-reaction occurred between TZSV and other tested viruses. The visual detection limit of the test strip for TZSV was 800 fold dilutions of TZSV-infected leaf samples. CONCLUSION: The mAbs were specific and the colloidal GICA strip developed in this study was convenient, fast and reliable for the detection of TZSV. The method could be applied for the rapid diagnosis and surveillance of TZSV in the field.