[The impact of LDL-C/HDL-C ratio on severity of coronary artery disease and 2-year outcome in patients with premature coronary heart disease: results of a prospective, multicenter, observational cohort study].

Objective: To explore the relationship between low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio with the severity of coronary artery disease and 2-yeat outcome in patients with premature coronary heart disease. Methods: This prospective, multicenter, observational cohort study is originated from the PROMISE study. Eighteen thousand seven hundred and one patients with coronary heart disease (CHD) were screened from January 2015 to May 2019. Three thousand eight hundred and sixty-one patients with premature CHD were enrolled in the current study. According to the median LDL-C/HDL-C ratio (2.4), the patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.4, n=1 867) and high LDL-C/HDL-C group (LDL-C/HDL-C>2.4, n=1 994). Baseline data and 2-year major adverse cardiovascular and cerebrovascular events (MACCE) were collected and analyzed in order to find the differences between premature CHD patients at different LDL-C/HDL-C levels, and explore the correlation between LDL-C/HDL-C ratio with the severity of coronary artery disease and MACCE. Results: The average age of the low LDL-C/HDL-C ratio group was (48.5±6.5) years, 1 154 patients were males (61.8%); the average age of high LDL-C/HDL-C ratio group was (46.5±6.8) years, 1 523 were males (76.4%). The number of target lesions, the number of coronary artery lesions, the preoperative SNYTAX score and the proportion of three-vessel coronary artery disease in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (1.04±0.74 vs. 0.97±0.80, P=0.002; 2.04±0.84 vs. 1.85±0.84, P<0.001; 13.81±8.87 vs. 11.70±8.05, P<0.001; 36.2% vs. 27.4%, respectively, P<0.001). Correlation analysis showed that there was a significant positive correlation between LDL-C/HDL-C ratio and preoperative SYNTAX score, the number of coronary artery lesions, the number of target lesions and whether it was a three-vessel coronary artery disease (all P<0.05). The 2-year follow-up results showed that the incidence of MACCE was significantly higher in the high LDL-C/HDL-C group than that in the low LDL-C/HDL-C group (6.9% vs. 9.1%, P=0.011). There was no significant difference in the incidence of all-cause death, cardiac death, myocardial infarction, stroke, revascularization and bleeding between the two groups. Cox multivariate regression analysis showed that the LDL-C/HDL-C ratio has no correlation with 2-year MACCE, death, myocardial infarction, revascularization, stroke and bleeding events above BARC2 in patients with premature CHD. Conclusion: High LDL-C/HDL-C ratio is positively correlated with the severity of coronary artery disease in patients with premature CHD. The incidence of MACCE of patients with high LDL-C/HDL-C ratio is significantly higher during 2 years follow-up; LDL-C/HDL-C ratio may be an indicator for evaluating the severity of coronary artery disease and long-term prognosis in patients with premature CHD.

[Comparative study of hypersensitive quantitative fecal immunochemical test and qualitative fecal occult blood test for colorectal cancer and advanced adenoma].

Objective: To evaluate the screening performance of hypersensitive quantitative fecal immunochemical test (hs-qFIT) and qualitative fecal occult blood test (FOBT) for colorectal cancer and advanced adenoma. Methods: Consecutive participants scheduled to undergo colonoscopy from April 2020 to April 2021 in Qilu Hospital of Shandong University were included in the study. All the participants were 50-75 years old and at moderate to high risk for colorectal cancer. Participants completed hs-qFIT and two kinds of qualitative FOBTs (colloidal gold method and chemical-immunization method) before colonoscopy. The sensitivities and specificities of hs-qFIT and two qualitative FOBTs for colorectal cancer and advanced adenoma were compared. Results: A total of 910 participants were enrolled in the study, including 451 males and 459 females, aged (59.6±6.4) years. There were 22 cases (2.4%) of colorectal cancer, 61 cases (6.7%) of advanced adenoma, 276 cases (30.3%) of non-advanced adenoma, 194 cases (21.3%) of non-adenomatous polyp, 85 cases (9.3%) of other colorectal lesion and 272 cases (29.9%) of non-colorectal lesion. The sensitivities of hs-qFIT for detecting colorectal cancer increased from 72.7% (95%CI: 49.6%-88.4%) to 100% (95%CI: 81.5%-100%) with cut-off value decreasing from 200 ng/ml to 10 ng/ml, and the sensitivities of both colloidal gold method and chemical-immunization method were 63.6% (95%CI: 40.8%-82.0%) (P=0.008). The detection stability of hs-qFIT for colorectal cancer was higher than colloidal gold method (P=0.016) and chemical-immunization method (P=0.031). The sensitivity for detecting advanced adenoma of hs-qFIT at 10 ng/ml was 52.5% (95%CI: 39.4%-65.2%), which was significantly higher than that of colloidal gold method (13.1%, 95%CI: 6.2%-24.8%, P<0.001) and chemical-immunization method (6.6%, 95%CI: 2.1%-16.7%, P<0.001). Conclusions: The sensitivity and detection stability of hs-qFIT for detecting colorectal cancer was higher than qualitative FOBT. Moreover, the sensitivity for detecting advanced adenoma can be further improved using a lower cut-off value.

Identifying systems delays in assessment, diagnosis, and operative management for testicular torsion in a single-payer health-care system.

INTRODUCTION: Testicular torsion (TT) is a common pediatric urologic emergency. Management of TT is time sensitive and often confirmed on scrotal Doppler ultrasound (DUS). Acquiring DUS, however, can result in delays in the management of TT, affecting testicular salvage rates. OBJECTIVE: The objective of this study is to identify delays in the assessment and diagnosis for patients presenting with TT to a Canadian academic hospital using patient flow analysis. STUDY DESIGN: A retrospective review was performed for patients presenting to the emergency department (ED) who received a scrotal DUS to rule out possible TT between 2012 and 2017. The primary outcome measured cycle-time measurements (median time) between points along the clinical flow pathway for a patient with suspected TT. The secondary outcome assessed diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of standard scrotal DUS components (Doppler flow, arterial waveform, heterogeneous echotexture). RESULTS: A total of 609 patients presented with an acute scrotum warranting a scrotal DUS to rule out TT; of which, 46 underwent scrotal exploration. Testicular salvage rate was 82.6% in the series (38 testes salvaged, 8 required orchiectomy). Median time from symptom onset to ED presentation for patients with possible TT was 4 h. After triage, a median of 79.8 min was required for ED physician assessment and an additional 48 min for scrotal DUS to be performed. Absence of Doppler flow on scrotal DUS had a 97.4% PPV for diagnosing TT confirmed during scrotal exploration. DISCUSSION: Almost 4 h of in-ED time is required from triage to surgical intervention for potential TT at the institution. One area of delay is the time needed to conduct a scrotal DUS (48-128 min; Fig. 1). This represents an area of opportunity for patient flow optimization through the use of standardized clinical pathways and diagnostic adjuncts, such as point-of-care ultrasound. This study is limited in its retrospective nature and does not include patients with overt signs of TT who underwent surgical detorsion without need for scrotal DUS. CONCLUSION: Patient flow delays to surgical intervention for patients with TT represent a preventable cause of orchiectomy in young men. This study identifies intervention points in patient-care flow pathways where delays to surgical intervention can be potentially reduced by up to 2 h. The findings support the need for further studies into the optimization of patient flow and management protocols to reduce delays in the diagnosis and management of TT.

Scavenger receptor class B type I mediates cell entry of hepatitis C virus.

This study assessed the functional role of human scavenger receptor class B type I (SR-BI) as a putative hepatitis C virus (HCV) receptor using Chinese hamster ovary (CHO) cells transfected with human SR-BI (CHO-huSR-BI). The expression of SR-BI by primary Tupaia hepatocytes (PTHs), human hepatocarcinoma cell line (HepG2) cells, untransfected CHO cells and CHO-huSR-BI cells was analysed by Western blotting. Receptor competition assays showed that anti-SR-BI antibodies that block the binding of soluble envelope glycoprotein E2 could prevent HCV infection. Pre-incubation of CHO-huSR-BI and HepG2 cells with anti-SR-BI antibodies resulted in marked inhibition of E2 binding. After incubation with HCV RNA-positive serum from a patient with chronic HCV infection, however, HCV infection could not be detected in CHO-huSR-BI cells, but was detected in PTHs. These results demonstrate that, whilst SR-BI represents an important cell surface molecule for HCV infection, the presence of SR-BI alone is insufficient for HCV entry.

In vitro hepatic differentiation of mesenchymal stem cells from human fetal bone marrow.

We examined whether human fetal mesenchymal stem cells (FMSCs) derived from fetal bone marrow were able to differentiate into functional hepatocyte-like cells in vitro. The surface phenotype of FMSCs was characterized by flow cytometry. To induce hepatic differentiation of FMSCs, we added hepatocyte growth factor, basic fibroblast growth factor and oncostatin M into the cell culture medium. After 21 days of hepatocyte induction, FMSCs expressed the hepatocyte-specific markers, alpha-fetoprotein and cytokeratin 18, as demonstrated by immunofluorescence staining. Differentiated FMSCs also demonstrated in vitro functions characteristic of liver cells, including albumin production, urea secretion and glycogen storage. In conclusion, fetal bone marrow-derived FMSCs are able to differentiate into functional hepatocytelike cells and may serve as a source of cells for liver disease therapy.

[Analysis on epidemiological and temporal-spatial distribution characteristics of hemorrhagic fever with renal syndrome in Shandong province, 2010-2016].

Objective: To analyze the epidemiological and temporal-spatial distribution characteristics of hemorrhagic fever with renal syndrome (HFRS) in Shandong province during 2010-2016 and provide references for developing prevention and control measures. Methods: Based on the data of Infectious Disease Reporting Information System in China, the incidence and temporal-spatial distribution of HFRS in Shandong from 2010 to 2016 were analyzed by spatial autocorrelation and space-time scan statistics. Results: A total of 9 114 HFRS cases were reported in Shandong during this period. The cases were mainly distributed in age group 30-70 years, and the male to female ratio of the cases was 2.63 ∶ 1. Most cases were farmers. The higher incidence rate was reported in southeastern Shandong, while the lower incidence rate was reported in northwestern Shandong. Among the epidemic periods, the highest incidence rate was 1.87/100 000 in 2013. The results of spatial autocorrelation and space-time scanning indicated that the high-high clusters of HFRS were concentrated in southeastern Shandong and then spread to central Shandong. The cluster mainly occurred from the end of 2011 to the first half of 2015. Both the incidence rate and the cluster decreased in 2016. Conclusions: The epidemic and cluster of HFRS still existed in Shandong from 2010 to 2016. The key areas for the prevention and control of HFRS were in southeastern and central Shandong.

Specificity of origin recognition by replication initiator protein in plasmids of the pT181 family is determined by a six amino acid residue element.

We have investigated the specificity of replication origin recognition by the initiator proteins of a set of six closely related Staphylococcus aureus plasmids, the pT181 family. These plasmids replicate by an asymmetric rolling-circle mechanism using plasmid-coded initiators that nick the replication origins and form a phosphotyrosine bond at the 5' nick terminus. Five of the plasmids are in different incompatibility groups and their initiator proteins do not cross-complement the cloned origins of any but their own plasmid. One pair is weakly incompatible and their initiator proteins and origins do cross-complement for replication in vivo. This pattern of cross-reactivity led to the prediction that the determinant of specificity would correspond to a homologously positioned set of six residues in the C-terminal domain of the protein, some 80 residues away from the active site tyrosine, that are divergent for all of the compatible plasmids and identical for the incompatible pair. Site-directed mutagenesis was used to exchange these six residues among three pairs of plasmids and these exchanges brought about the predicted switching of origin recognition specificity. Single substitution within this six residue set reduced or eliminated the activity of the protein but did not alter the origin recognition specificity. These six and flanking residues cannot form an amphipathic alpha-helix nor do they conform to the classical helix-turn-helix or other known DNA binding motifs. A novel type of interaction is suggested in which the protein binds to its recognition site, bends and melts the DNA, and causes or enhances the extrusion of an adjacent cruciform containing the nick site. This configuration would juxtapose the nicking target and the active site tyrosine residue and would unwind the highly G + C-rich replication origin.

Improved Cuff Technique for Establishing a Mouse-Rat Heterotopic Cardiac Xenotransplantation Model.

BACKGROUND: The small animal model of cardiac transplantation is the most common model in organ transplantation studies. The cervical heterotopic transplantation is widely performed because this allows for direct observation of the graft heartbeat and contributes to early prediction of graft rejection. OBJECTIVE: A mouse-rat cervical heterotopic cardiac xenotransplantation model was modified with respect to the anesthesia method, cardiac graft harvesting method, and perioperative treatment. These improvements ensure the stability and reliability of xenotransplantation models for in vivo studies of immune-mediated graft rejection. METHODS: After establishing isoflurane inhalation anesthesia, the donors' hearts were harvested. The experimental method involved separate ligation of the left and right superior venae cavae; the other blood vessels were ligated in a cluster. Both the donor and recipient animals were placed on a heating pad intraoperatively to maintain a body temperature of 37-40 °C. The model establishment was divided into 3 stages: practice, stabilization, and stereotyping. The surgical success rate and operation time were recorded. Specimens were harvested at different time points for histopathological examination. RESULTS: The anesthetic effect of isoflurane was well maintained, and no animals died of adverse anesthetic events. Body temperature was maintained at 37-40 °C which effectively shortened the time to restoration. The modification of the cardiac graft harvesting method is conducive to rebeating of the donor heart. The success rates in the stabilization and stereotyping stages were significantly higher than that in the practice stage (P < .05). The operation time in the stabilization and stereotyping stages were significantly shorter than those in the practice stage (P < .05). Histopathological examination revealed thrombosis formation, interstitial hemorrhage, and inflammatory cell infiltration in the donor hearts. CONCLUSION: Our findings suggest that the mouse-rat cervical heterotopic cardiac xenotransplantation model is the ideal animal model for studying xenograft rejection.

Intestinal permeability and bacterial translocation following small bowel transplantation in the rat.

In addition to its role in absorbing nutrients, the intestinal mucosa provides an important barrier against toxins and bacteria in the bowel lumen. The present study evaluated gut barrier function following orthotopic (in continuity) intestinal grafting in rats. Graft histology, intestinal permeability, and bacterial translocation to the grafted mesenteric lymph nodes, the host's liver, and the host's spleen were assessed on the 3rd, 5th, and 7th postoperative days. The study group received no immunosuppression after allotransplantation. The two control groups included rats with isografts and rats with cyclosporine-treated allografts. On the 7th POD, the study animals had moderate transmural inflammation due to rejection, with normal histology in the isografts and CsA-treated allografts; increased intestinal permeability, measured by urinary excretion of oral 51Cr-EDTA (P less than 0.01); and increased number of bacteria in the MLN and spleen (P less than 0.05). The number of bacteria in the MLN and spleen of the study group positively correlated with the changes in intestinal permeability (P less than 0.05). Rejection of the orthotopic intestinal graft leads to increased intestinal permeability and bacterial translocation from the lumen of the graft to the host's reticuloendothelial system. Measures to improve gut barrier function and antibiotic therapy during rejection episodes may help reduce the incidence of septic complications after intestinal grafting.

A comparison of heterotopic and orthotopic intestinal transplantation in rats.

Two surgical techniques are commonly used for small intestinal transplantation: heterotopic (accessory) intestinal grafting (HIT), where the small bowel is initially defunctioned with restoration of intestinal continuity at a later date, and orthotopic (in continuity) intestinal grafting (OIT), where the small bowel is immediately anastomosed to the native intestine. The present experiments were undertaken to compare the advantages and disadvantages of these two surgical models. Graft barrier function (intestinal permeability), intestinal histology, and graft survival were evaluated after heterotopic and orthotopic intestinal transplantation in the following groups of rats: group 1: isografts, group 2: untreated allografts, group 3: low-dose cyclosporine-treated allografts (subcutaneous CsA 2 mg/kg/day), and group 4: high-dose CsA-treated allografts (subcutaneous CsA 4 mg/kg/day). Intestinal permeability was consistently higher after HIT than OIT in all of the groups (ANOVA; P less than 0.01). Histological evidence of rejection appeared earlier after HIT than OIT (HIT 5th postoperative day (POD); OIT 7th POD; P less than 0.05). The mean survival of untreated allografts was longer after HIT than OIT (HIT 15.7 +/- 6 days, OIT 9.2 +/- 1 days, P less than 0.05). The rats treated with low-dose CsA after OIT lost weight and died of rejection after a mean survival time of 17.7 +/- 2 days, while the rats treated with low-dose CsA after HIT remained well until sacrifice on POD 28 (P less than 0.01). The rats with isografts and rats with allografts treated with high-dose CsA remained well after HIT and OIT until sacrifice on the 28th POD. These data suggest that nutrients and other factors in the succus entericus may improve gut barrier function and delay the onset of rejection after OIT. However, rejection of the orthotopic intestinal graft is usually fatal, while rejection of the heterotopic graft is often surprisingly well tolerated. These factors must be taken into consideration when choosing a surgical technique for intestinal transplantation in humans.

Trends in physician-diagnosed asthma prevalence in Manitoba between 1980 and 1990.

We attempted to assess recent changes in the prevalence of physician-diagnosed asthma and the possible influence of diagnostic exchange on these trends. The routinely collected data of the provincial Health Insurance Plan (physicians' claims) were used to determine the annual prevalence of physician-diagnosed asthma in Manitoba. Results indicate that the prevalence of physician-diagnosed asthma increased for all age groups in both male and female subjects between 1980 and 1990. The average increases were the highest in the age group 5 to 14 years for both sexes. The average increases varied with age and there were significant differences between the two sexes. There was evidence of increasing diagnostic exchange, that is, a tendency to label patients with asthma instead of alternative diagnoses. This was particularly prominent in those younger than 35 years of age. However, the increased prevalence of physician-diagnosed asthma, even for the younger population, cannot be fully explained by diagnostic exchange.

A two-year study of acceptability, side effects, and effectiveness of Norplant and Norplant-2 implants in the People's Republic of China.

A large scale, phased investigation of NORPLANT contraceptive systems was conducted in the People's Republic of China. The first phase comprehended 1,200 women in four cities. Expanded trials included 11,918 women at 12 major centers and at sub-centers by 31 May 1987. At that date 4,676 NORPLANT capsule subjects and 1,089 rod subjects had completed one year of use, 1,381 capsule acceptors had completed two years as had 197 rod users. Gross pregnancy rates were less than 0.1 per 100 for each implant type both at one and at two years. Continuation rates were 94 per 100 for each implant type at one year, and were 82.0 and 83.6 per 100 among users of NORPLANT capsule and rod implants, respectively, at two years. Disruption of menstrual function was the dominant reason for termination, but mean hemoglobin levels increased in each of the nine centers reporting values at admission and at one year. First year gross cumulative termination rates for medical reasons were 1.2 to 1.3 per 100, reaching 3.8 and 5.6 per 100 for capsule and rod implants, respectively, at two years. Microdose contraception with these levonorgestrel-releasing implants appears to be a highly acceptable and effective modality suitable for Chinese women. NORPLANT implants are now approved by the national drug regulatory agency for general use in China.

The min-max function differentiation and training of fuzzy neural networks.

This paper discusses the Delta-rule and training of min-max neural networks by developing a differentiation theory for min-max functions, the functions containing min (wedge) and/or max (V) operations. We first prove that under certain conditions all min-max functions are continuously differentiable almost everywhere in the real number field R and derive the explicit formulas for the differentiation. These results are the basis for developing the Delta-rule for the training of min-max neural networks. The convergence of the new Delta-rule is proved theoretically using the stochastic theory, and is demonstrated with a simulation example.

Radiographic findings in Langerhans' cell disease affecting the mandible.

The radiographic features of histopathologically diagnosed mandibular Langerhans' cell disease are described for 29 cases of the condition. We divided the patients into two groups: adults (age 27 to 60 years) and juveniles (age 1.5 to 15 years). A characteristic sign in juveniles was an osteolytic lesion with an uneven margin and either a continuous or discontinuous periosteal reaction. Because of the wide variability in radiographic presentation in adults, it was very difficult to differentiate this from other lesions in adults on the basis of radiologic criteria.

[Analysis of treatment in 84 cases of severe pancreatitis].

84 patients who suffered from severe pancreatitis were treated in our hospital. In order to compare the efficacy of different therapy in early, middle and recent stages, the patients were divided into 3 groups. In early stage group (Jan, 1983-Dec, 1985) the treatment mainly was surgical drainage of the pancreas, the mortality was 72.7%. In middle stage group (Jan, 1986-Jan, 1989) the main treatment consisted of incision and decompression of pancreatic capsule, debridement of pancreas and inhibiting pancreatic secretion, the mortality decreased to 34.8%. In recent stage group (Jan, 1990-Jan, 1994) the therapy was Integrated Chinese Traditional and Western Medicine which comprised the method used in middle stage with TCM including acupuncture depending upon the syndrome. The mortality further lowered to 25.6%.

Elevated vascular endothelial growth factor levels induce hyperpermeability of endothelial cells in hantavirus infection.

OBJECTIVE: To investigate the role of vascular endothelial growth factor (VEGF) in haemorrhagic fever with renal syndrome (HFRS). METHODS: VEGF, soluble VEGF receptor (sVEGFR)-2, angiopoietin (Ang)-1, tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels were measured in serum samples from 68 patients with HFRS. Cultured human umbilical vein endothelial cells (HUEVCs) were infected by Hantaan virus (HTNV) and/or stimulated with recombinant VEGF; dextran permeability of the cells was determined. Claudin-1 and vascular endothelial (VE)-cadherin levels were determined by real-time reverse transcription-polymerase chain reaction and Western blot analyses. RESULTS: Serum VEGF, TNF-α and IFN-γ levels were significantly elevated, whereas sVEGFR2 and Ang-1 levels were reduced, during the acute phase of HFRS. In vitro cell permeability was unaffected by HTNV infection or VEGF stimulation alone, but the combination of HTNV infection and VEGF treatment significantly increased the permeability of endothelial cell monolayers in a time-dependent manner. Claudin-1 and VE-cadherin were downregulated at both the mRNA and protein level by combined HTNV infection and VEGF stimulation. CONCLUSIONS: Elevated VEGF induced by HTNV infection may play an important role in the vascular hyperpermeability that is characteristic of HFRS.

Elevated serum concentrations of inflammatory cytokines and chemokines in patients with haemorrhagic fever with renal syndrome.

OBJECTIVE: Prospective case-control study, undertaken to investigate serum cytokine and chemokine concentrations during all clinical phases and in different clinical types of haemorrhagic fever with renal syndrome (HFRS). METHODS: Serum was collected at various disease phases from patients with HFRS (n = 35) and healthy control subjects (n = 10). Tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-4, interferon (IFN)-γ, IL-8, interferon inducible protein-10 (IP-10) and chemokine (C-C motif) ligand 5 (also known as 'regulated upon activation, normal T-cell expressed and secreted' [RANTES]) were quantified using commercial enzyme-linked immunosorbent assay kits. RESULTS: Serum concentrations of TNF-α, IL-6, IFN-γ, IL-8, IP-10 and RANTES (but not IL-4) were significantly higher in patients compared with controls. Highest concentrations were generally found during the febrile, hypotensive and oliguric disease phases, as well as in clinically severe and critical cases. CONCLUSION: Serum concentrations of proinflammatory cytokines and chemokines increased in line with disease severity in HFRS patients.