Celastrol ameliorates energy metabolism dysfunction of hypertensive rats by dilating vessels to improve hemodynamics.

The impact of hypertension on tissue and organ damage is mediated through its influence on the structure and function of blood vessels. This study aimed to examine the potential of celastrol, a bioactive compound derived from Tripterygium wilfordii Hook F, in mitigating hypertension-induced energy metabolism disorder and enhancing blood perfusion and vasodilation. In order to investigate this phenomenon, we conducted in vivo experiments on renovascular hypertensive rats, employing indirect calorimetry to measure energy metabolism and laser speckle contrast imaging to evaluate hemodynamics. In vitro, we assessed the vasodilatory effects of celastrol on the basilar artery and superior mesenteric artery of rats using the Multi Wires Myograph System. Furthermore, we conducted preliminary investigations to elucidate the underlying mechanism. Moreover, administration of celastrol at doses of 1 and 2 mg/kg yielded a notable enhancement in blood flow ranging from 6 to 31% across different cerebral and mesenteric vessels in hypertensive rats. Furthermore, celastrol demonstrated a concentration-dependent (1 × 10-7 to 1 × 10-5 M) arterial dilation, independent of endothelial function. This vasodilatory effect could potentially be attributed to the inhibition of Ca2+ channels on vascular smooth muscle cells induced by celastrol. These findings imply that celastrol has the potential to ameliorate hemodynamics through vasodilation, thereby alleviating energy metabolism dysfunctions in hypertensive rats. Consequently, celastrol may hold promise as a novel therapeutic agent for the treatment of hypertension.

Diagnostic performance and prognostic value of circulating tumor DNA methylation marker in extranodal natural killer/T cell lymphoma.

Circulating tumor DNA (ctDNA) carries tumor-specific genetic and epigenetic variations. To identify extranodal natural killer/T cell lymphoma (ENKTL)-specific methylation markers and establish a diagnostic and prognosis prediction model for ENKTL, we describe the ENKTL-specific ctDNA methylation patterns by analyzing the methylation profiles of ENKTL plasma samples. We construct a diagnostic prediction model based on ctDNA methylation markers with both high specificity and sensitivity and close relevance to tumor staging and therapeutic response. Subsequently, we built a prognostic prediction model showing excellent performance, and its predictive accuracy is significantly better than the Ann Arbor staging and prognostic index of natural killer lymphoma (PINK) risk system. Notably, we further establish a PINK-C risk grading system to select individualized treatment for patients with different prognostic risks. In conclusion, these results suggest that ctDNA methylation markers are of great value in diagnosis, monitoring, and prognosis, which might have implications for clinical decision-making of patients with ENKTL.

Prepayment Model of Supply Chain Financing Based on Internet of Things and Machine Learning Algorithm.

Nowadays, the relationship between all kinds of things is constantly strengthened, and the regional restrictions on things are also constantly weakened, especially in the aspect of trade. In the past, people could only buy some basic goods in a relatively small area if they wanted to buy them in a relatively small area, but now the situation is very different. People's dependence on traders is gradually decreasing; that is to say, the traditional advantages of traders are gradually losing. Particularly, in today's fierce competition, survival of the fittest, and limited profits, the entire trade industry is facing a lot of impacts, not to mention the survival of traders relying on this industry. Therefore, traders must think of a new way to adapt to the characteristics of the new era, to continue to make profits and maintain their own survival. In fact, for the whole industry, this is also the most urgent problem to be solved. This study mainly explores the above problems and puts forward some feasible methods to solve the problems, hoping to cause some thinking of the industry personnel, so that they can modify and adjust their working mode. In addition, it should be emphasized that the mode of using Internet of things and machine learning to achieve the purpose of innovation is of great practical significance.

Performance evaluation of the BC-720 auto hematology analyzer and establishment of the reference intervals of erythrocyte sedimentation rate in healthy adults.

Background: Erythrocyte sedimentation rate (ESR) is a new reporting parameter of the BC-720 auto hematology analyzer; however, no biological reference interval for healthy adults has been established for this parameter. Methods: Outpatients or hospitalized patients with ESR test orders were selected. The ESR was measured by the standard method of ESR (Westergren) recommended by the International Council for Standardization in Hematology (ICSH), the BC-720 hematology analyzer, and the LBY-XC40B auto ESR analyzer. The data were statistically analyzed and compared among different methods. The repeatability and carryover rate (CR) of the BC-720 were assessed in randomly selected samples for each range segment. Blood Samples from three hospitals in China were collected, and the reference interval of the BC-720 ESR was determined. Results: The ESR results measured by the BC-720 correlated well with the Westergren method (r=0.957, y = 0.359 + 1.016x), and there was no significant difference between these two methods (P>0.05). The correlation between LBY-XC40B auto ESR analyzer and Westergren was y = 1 + 1.25x and r=0.856. The BC-720 ESR has good repeatability [standard deviation (SD) ≤1 mm/h, coefficient of variation (CV) ≤5%], and the CR was less than 1%. The 95th percentile of the biological reference interval for BC-720 ESR is 15 mm/h for men and 24 mm/h for women. Conclusions: The Mindray BC-720 ESR showed high accuracy and good repeatability, which provided a faster, safer, and more reliable method to measure ESR. The reference intervals for BC-720 ESR could guide better clinical decisions for the laboratories utilizing this new method.

Postoperative online follow-up improves the quality of life of patients who undergo extraction of impacted madibular third molars: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of online follow-up on the quality of life of patients who undergo extraction of impacted mandibular third molars. MATERIALS AND METHODS: This study enrolled patients with impacted mandibular third molars who were treated at the Department of Oral and Maxillofacial Surgery of the Stomatological Hospital at Southern Medical University and divided them into test and control groups. The test group received an online follow-up on the first, third, and fifth days after tooth extraction, while the control group was not followed up with. Patients in both groups were reexamined on the postoperative seventh day, completing the postoperative symptom severity (PoSSe) scale to comprehensively and quantitatively evaluate their quality of life after tooth extraction. A visual analogue scale (VAS) was used to evaluate the degree of approval for an online follow-up after tooth extraction by 20 senior doctors (≥ 40 years old) and 20 young doctors (<4 0 years old). RESULTS: The PoSSe scale scores of the remaining options in the test group were significantly lower than those in the control group. The VAS score of senior doctors for online follow-up was significantly lower than that of young doctors. CONCLUSIONS: A postoperative online follow-up effectively improved the quality of life of patients who underwent extraction of impacted mandibular third molars. Compared with senior doctors, young doctors were more likely to approve an online follow-up after tooth extraction. CLINICAL RELEVANCE: Online medical care can be considered as an auxiliary tool to improve the effect of oral treatment.

Preparation of artificial antigen and egg yolk-derived immunoglobulin (IgY) of citrinin for enzyme-linked immunosorbent assay.

OBJECTIVE: To prepare artificial antigens and anti-citrinin egg yolk-derived immunoglobulin (IgY) to build an enzyme-linked immunosorbent assay (ELISA) for citrinin (CTN). METHODS: CTN was conjugated with bovine serum albumin (BSA), ovalbumin (OVA) with formaldehyde condensation method to prepare artificial antigens and identified by ultraviolet (UV) spectrometry and Infrared (IR) spectrometry. Artificial antigens for CTN and anti-CTN IgY were purified with polyethylene glycol two-step precipitation method and identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). ELISA with IgY was established. Cross-reactivity of IgY with various structural similarities to CTN and possible co-occurrence with CTN in agricultural commodities were studied. RESULTS: UV and IR absorption spectra suggested that CTN was correlated with the carrier protein of BSA or OVA. SDS-PAGE patterns showed that the anti-CTN IgY was almost pure with a molecular weight of approximate 100 KD. The indirect competitive ELISA showed that the detection limit of CTN was 10 ng x mL(-1), with a good linearity ranging 20-640 ng x mL(-1). CONCLUSION: Artificial antigens of CTN can be successfully synthesized. The established ELISA can be used to determine CTN- contaminated samples.

Adrenaline induces chemoresistance in HT-29 colon adenocarcinoma cells.

Psychological distress and its ensuing chronic elevation of plasma catecholamines (adrenaline and noradrenaline) lead to poor response of tumors to chemotherapy, and constitute a poor prognostic factor for survival. Colorectal cancer patients suffer from various forms of psychological stress reflected in elevated plasma catecholamines, and their cancer cells express adrenergic receptors. Our objective was to investigate whether adrenergic activation contributes to the chemoresistance of colon cancers, and to explore the signal transduction pathway involved in the activation. The mRNA expression of the ABCB1 gene (previously MDR1) in human colon carcinoma HT-29 cell line was measured after treatment with an adrenergic receptor agonist (adrenaline) and various antagonists (propranolol, prazosin, and yohimbine). The function of P-glycoprotein, the protein product of the ABCB1 gene, was assessed by rhodamine 123 (Rh123)-retention assay, and chemosensitivity was determined by evaluating the cytotoxicity of 5-fluorouracil (5-FU) on the tumor cells. Increased ABCB1 mRNA expression and P-glycoprotein function levels in HT-29 cells by adrenaline was dose-dependent. This was accompanied by promotion of Rh123 efflux, and resistance to the growth-inhibiting effect of 5-FU in the tumor cells. The alpha2-adrenergic receptor antagonist yohimbine completely abolished the induction of ABCB1 mRNA, the stimulatory effect of adrenaline on Rh123 efflux, and the growth-inhibiting effect of 5-FU. The alpha1-adrenergic receptor and beta-adrenergic receptor antagonists did not inhibit the induction of ABCB1. The stimulating effects were coupled with extracellular receptor kinase 1/2 (Erk1/2) phosphorylation, but were not associated with protein kinase A activity. We conclude that adrenaline induces multidrug resistance in colon cancer cells by upregulating ABCB1 gene expression via alpha2-adrenergic receptors, and such effects were associated with the mitogen activated protein kinase (MAPK) pathway.

Upregulation of mitochondrial gene expression in PBMC from convalescent SARS patients.

The observations that Lymphopenia is common in severe acute respiratory syndrome (SARS) patients and that peripheral blood mononuclear cell (PBMC) could be infected by SARS-CoV indicate that PBMC could be useful in identifying the gene expression profile in convalescent patients and tracing the host response to SARS-CoV infection. In this study, the altered genes expressions in the PBMC of convalescent SARS patients were investigated with suppression subtractive hybridization (SSH). We found that genes encoded by mitochondrial DNA (mtDNA) were obviously upregulated, while mitochondria were now found to be closely connected with antiviral immunity. The identification of a viral gene, M, in SSH cDNA library shows the long-term existence of SARS-CoV in vivo. In addition, some oxidative stress sensitive genes, heat shock proteins, transcription factors, and cytokines showed remarkable elevation. Thin-section electron microscope shows increased lysosome-like granule and mitochondria in PBMC of patients. These results provide important intracellular clue for tracing host response to SARS-CoV infection and suggest a role of mitochondria in that process.

Serum neopterin for early assessment of severity of severe acute respiratory syndrome.

Neopterin and C-reactive protein (CRP) concentrations were determined in serum samples from 129 severe acute respiratory syndrome (SARS) patients and 156 healthy blood donors. In the patients with confirmed SARS, an early neopterin elevation was detected already at the day of onset of symptoms and rose to a maximum level of 45.0 nmol/L 3 days after the onset. All SARS patients had elevated neopterin concentrations (>10 nmol/L) within 9 days after the onset. The mean neopterin concentrations were 34.2 nmol/L in acute sera of SARS patients, 5.1 nmol/L in convalescent sera, and 6.7 nmol/L in healthy controls. In contrast, the mean CRP concentrations in both acute and convalescent sera of SARS patients were in the normal range (<10 mg/L). Serum neopterin level in SARS patients was associated with fever period and thus the clinical progression of the disease, while there was no significant correlation between the CRP level and the fever period. Serum neopterin may allow early assessment of the severity of SARS. The decrease of neopterin level was found after steroid treatment, which indicates that blood samples should be collected before steroid treatment for the neopterin measurement.

Th2 predominance and CD8+ memory T cell depletion in patients with severe acute respiratory syndrome.

UNLABELLED: The immune spectrum of severe acute respiratory syndrome (SARS) is poorly understood. To define the dynamics of the immune spectrum in SARS, serum levels of cytokines, chemokines, immunoglobulins, complement and specific antibodies against SARS-associated coronavirus (SARS-CoV) were assayed by enzyme-linked immunosorbent assay (ELISA), and phenotypes of peripheral lymphocytes were analyzed by flow cytometry in 95 SARS-infected patients. Results showed that interleukin (IL)-10 and transforming growth factor beta (TGF-beta) were continuously up-regulated during the entirety of SARS. Regulated on activation normally T cell-expressed and secreted (RANTES) levels were decreased, while monocyte chemoattractant protein-1 (MCP-1) was elevated in acute patients. Immunoglobulins and complement were elevated during the first month of SARS. Both serum-positive rates and titers of specific IgM and IgG antibodies responding to SARS-CoV peaked at days 41-60 from the onset of SARS. CD4+ and CD8+ T lymphocytes decreased significantly in acute-phase. CD3+CD8+CD45RO+ T lymphocytes were decreased by 36.78% in the convalescent patients. CONCLUSION: SARS-CoV seemed to elicit effective humoral immunity but inhibited cellular immunity, especially CD8+ memory T lymphocytes over time. Prolonged overproduction of IL-10 and TGF-beta may play an important role in the disease.

[The value of Roferon-A combined with hepatic artery chemoembolization and portal vein chemotherapy after radical resection in hepatocellular carcinoma for preventing recurrence].

OBJECTIVE: To explore the change of T cell subsets in patients suffered from hepatocellular carcinoma (HCC) before and after hepatectomy, and study the value of Roferon-A (interferon alpha-2a) combined with hepatic artery chemoembolization (HACE) and portal vein chemotherapy (PVC) after radical resection of HCC for preventing recurrence. METHODS: On 75 HCC patients, PVC and HACE were respectively given at 2 weeks and 4 weeks after radical tumor resection. In 2nd week after surgery, 33 cases of them accepted Roferon-A treatment for 1 week. Seventy-two patients were followed up over 3 years. Effect of Roferon-A combined with HACE and PVC on postoperative recurrence rate was compared with that of HACE and PVC. Changes of T cell subsets in peripheral blood were examined with labeled monoclonal antibodies before and after hepatectomy or using interferon. Forty cholecystolithiasis patients received cholecystectomy were used as the controls. RESULTS: CD(3)(+) and CD(4)(+) cells in peripheral blood were reduced in patients with HCC. After hepatectomy, they declined further with decrease in CD(4)(+)/CD(8)(+) ratio. The results returned to pre-operative level at the end of 4th week after surgery. The CD(3)(+), CD(4)(+) cells and the CD(4)(+)/CD(8)(+) ratio increased remarkably following the use of Roferon-A. The 1-, 2- and 3-year recurrence rates of patients treated with HACE, PVC and Roferon-A in combination were 0%, 6.2% and 15.6%, respectively, while those treated with HACE and PVC were 5.0%, 12.5% and 27.5%, respectively. CONCLUSION: Patients with HCC suffer from marked immuno-suppression which became ever more severe after hepatectomy, combined use of HACE, PVC and Roferon-A is superior to only HACE and PVC by decreasing the recurrence rate.

A cellular protein specifically binds to the 3'-terminal sequences of hepatitis C virus intermediate negative-strand RNA.

OBJECTIVE: To study the mechanism of the cellular proteins involved in the process of replication of hepatitis C virus (HCV) negative-strand RNA. METHODS: Ultraviolet (UV) cross-linking was used to identify the cellular proteins that would bind to the 3'-end of HCV negative-strand RNA. Competition experiment was used to confirm the specificity of this binding, in which excess nonhomologous protein and RNA transcripts were used as competitors. The required binding sequence was determined by mapping, then the binding site was predicted through secondary structure analysis. RESULTS: A cellular protein of 45 kD (p45) was found to bind specifically to the 3'-end of HCV negative-strand RNA by UV cross-linking. Nonhomologous proteins and RNA transcripts could not compete out this binding, whereas the unlabeled 3'-end of HCV negative-strand RNA could. Mapping of the protein-binding site suggested that the 3'-end 131-278nt of HCV negative-strand RNA was the possible protein-binding region. Analysis of RNA secondary structure presumed that the potential binding site was located at 194-GAAAGAAC-201. CONCLUSION: The cellular protein p45 could specifically bind to the secondary structure of the 3'-end of HCV intermediate negative-strand RNA, and may play an important role in HCV RNA replication.