Prodigiosin improves acute lung injury in a rat model of rheumatoid arthritis via down-regulating the nuclear factor kappaB/nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 signaling pathway.

Prodigiosin (PRO) is a natural pigment that possesses multiple activities, covering anti-tumor, anti-bacteria, and immunosuppression. This study is committed to an investigation into the underlying function and the certain mechanism of PRO in acute lung damage followed by rheumatoid arthritis (RA). Cecal ligation and puncture (CLP) method was implemented to trigger a rat lung injury model, and a rat RA model was constructed with the help of rheumatoid arthritis induced by collagen. Prodigiosin was administered to intervene in the rats' lung tissues post-treatment. The expressions of pro-inflammatory cytokines (interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 were determined. Western blot was carried out to detect anti-surfactant protein A (SPA), anti-surfactant protein D (SPD), apoptosis-concerned proteins (Bax, cleaved-caspase-3, Bcl-2, and pro-caspase-3), the nuclear factor-kappaB (NF-κB)/nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3)/apoptosis-concerned speckle-like protein (ASC)/caspase-1 signaling pathway. The apoptosis of pulmonary epithelial tissues was checked via TUNEL assay, as corresponding kits were adopted to confirm the activity of lactate dehydrogenase (LDH) and the levels of oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Prodigiosin ameliorated the pathological damage of CLP rats. Prodigiosin alleviated the production of inflammatory and oxidative stress mediators. In the RA rats with acute lung injury, prodigiosin hampered apoptosis in the lung. Mechanistically, prodigiosin hinders the activation of the NF-κB/NLRP3 signaling axis. In conclusion: prodigiosin relieves acute lung injury in a rat model of rheumatoid arthritis by exerting anti-inflammatory and anti-oxidative effects through downregulating the NF-κB/NLRP3 signaling axis.

Predisposing factors for person-to-person transmission of severe fever with thrombocytopenia syndrome bunyavirus.

Person-to-person transmission of severe fever with thrombocytopenia syndrome virus (SFTSV) is a new threat to human health. Here we report an outbreak of nosocomial person-to-person transmission of SFTS. Among eight persons with face-to-face contact distance ≤50 cm and/or exposure time ≥30 min to the index patient, six became infected. Only one of the 17 persons with exposure distance ≥50 cm and exposure time ≤30 min became infected (75% vs 6.25%, P < 0.001). Epidemiological investigation revealed high viral load, bloody secretions and bleeding, exposure time, and distance as the key factors in person-to-person transmission.

Breast ductal carcinoma in situ with micro-invasion versus ductal carcinoma in situ: a comparative analysis of clinicopathological and mammographic findings.

AIM: To determine the differences in clinicopathological and mammographic findings between ductal carcinoma in situ (DCIS) and ductal carcinoma in situ with micro-invasion (DCIS-MI) and explore clinicopathological and mammographic factors associated with DCIS-MI. MATERIALS AND METHODS: All DCIS patients with or without micro-invasion who underwent preoperative mammography at The Affiliated Hospital of Qingdao University from January 2016 through June 2020 were identified retrospectively. The correlations of clinicopathological findings with DCIS-MI were evaluated using univariate and multivariate binary logistic regression analyses. Imaging findings were compared between the groups by using the Pearson chi-square test. RESULTS: A total of 445 DCIS lesions and 151 DCIS-MI lesions were included in the final analysis. Large extent (≥2.7 cm), high nuclear grade, comedo-type, negative progesterone receptor (PR), negative oestrogen receptor (ER), high Ki-67 and axillary lymph node metastasis were more frequently found in DCIS-MI than in DCIS (all p<0.05), and the first four of these were found to be independent predictors of DCIS-MI in the multivariate analysis (all p<0.05). Regarding imaging findings, compared to DCIS, DCIS-MI showed fewer occult lesions and more lesions with calcifications in mass, asymmetry, and architectural distortion (p=0.004). Grouped calcifications were usually associated with DCIS, while regional calcifications were commonly found in DCIS-MI (p<0.05). CONCLUSION: Large extent, high nuclear grade, comedo-type and negative PR were found to be independent predictors of DCIS-MI. Lesions with calcifications and regional calcifications were more likely associated with DCIS-MI on mammography.

[Role of histological evaluation of periprosthetic tissue in diagnosis of periprosthetic joint infection].

Objective: To evaluate the role of histologicalpathology in the diagnosis of periprosthetic joint infection. Methods: A total of 145 cases of joint arthroplasty during October 2017 and October 2018 from Beijing Jishuitan Hospital were collected. There were 23 cases of infection, including knee joint arthroplasty (12 cases) and hip arthroplasty (11 cases). There were 17 females and 6 males. Patients' age ranged from 39 to 76 years (mean 63 years). The infection was diagnosed if there were >5 neutrophils per high power field in at least 5 high power field. The permanent sections were examined twice separately by two pathologists, and the interval time of histologic examination was at least two weeks. Sensitivity (SE), specificity (SP), positive predictivevalue (PPV), and negative predictive value (NPV) were calculated. The consistency evaluation of histologic examination of two pathologists was calculated by Kappa analysis. Results: The neutrophil cells could locate scattered or focally in the synovium tissue of periprosthetic joint infection. Somewhere, the infiltration of vessel and the perivascular distribution could also exist. Opportunity coincidence rate between two pathologists was 91.3% (Kappa=0.817). The results showed that SE was 60.9%, SP was 100.0%, NPV was 93.1%, PPV was 100.0%. Conclusions: The presence of polymorphonuclear cells in histologic examination is correlated with infection. There was high consistency between histologic examination and clinical diagnosis of joint arthroplasty.

The effect of transesophageal echocardiography in the surgical treatment of tetralogy of Fallot.

OBJECTIVE: To investigate the effect of transesophageal echocardiography (TEE) in the surgical treatment of tetralogy of Fallot. PATIENTS AND METHODS: 98 patients with tetralogy of Fallot received and cured by Zhengzhou Cardiovascular Hospital (Zhengzhou No. 7 People's Hospital) from January 2015 to January 2017 were selected as the study objects. All patients were examined by TEE before surgery, and the pulmonary artery index (PAI) and pulmonary vein index (PVI) were measured, so as to analyze the effect of TEE in the surgical treatment of tetralogy of Fallot. Among the 98 patients, 12 patients were diagnosed with intensive care unit (ICU) retention, 23 patients were diagnosed with respirator assisted respiration extension, 8 patients were diagnosed with low cardiac output syndrome, and 10 patients were diagnosed with respiratory tract infection, which indicated that TEE could diagnose conditions after radical operation of tetralogy of Fallot. RESULTS: The calculation results showed that the PAI was (171.37±58.39) mm2/m2 and the PVI was (282.46±54.37) mm2/m2. The Pearson correlation analysis showed that the correlation between them was good (r=0.821, p<0.001). TEE had good specificity and sensitivity in the diagnosis of respirator assisted respiration extension, ICU retention, and low cardiac output syndrome after radical surgery of tetralogy of Fallot. CONCLUSIONS: TEE can predict the occurrence of respirator assisted respiration extension, ICU retention and low cardiac output syndrome of patients after radical surgery by evaluating the PAI and PVI of patients with tetralogy of Fallot.

Repeated whole-lung lavage for unremitting pulmonary alveolar proteinosis: a eight-year follow-up of a case.

Pulmonary alveolar proteinosis (PAP) is a rare clinical syndrome that was first described in 1958. To date, whole-lung lavage (WLL) is still the gold-standard therapy for PAP. Herein, we report the case of a male patient who was diagnosed with PAP by open-lung biopsy 8 years prior to presentation at our clinic. The man underwent his first WLL in 2004 and showed marked clinical and radiological improvement after the operation. However, after his original presentation, proteinaceous material continued to accumulate in his lungs. Lavage was performed four additional times, but these attempts failed to arrest the decline in pulmonary function. Each lavage resulted in significant, although transient, clinical improvement.

Pulsed electrospray for mass spectrometry.

Pulsed electrospray has been developed and been reported for the first time. This new technique is based on the principle of pulsed ion sources, combined with the conventional electrospray. The pulsed ion spray was realized by a homemade pulsed HV circuit and was monitored by a digital microscope and an oscilloscope. Results show that the pulsed ESI device can be operated under proper conditions for a clear on-and-off spray process and that the device was kept in good electric contact for electrospray when pulsed HV was on. A pulsed ion current and pulsed mass spectra can be achieved with this pulsed ESI device. Furthermore, it has been noted that, under the same conditions (i.e., shape and size of sprayer tip, distance from sprayer tip to sampling nozzle, and other parameters for mass spectrometer), stable electrospray could be obtained for lower flow rates with a pulsed spray device. This experimental fact indicates the possible reduction in the total sample consumed could be realized by exploiting this novel design.

Immunobiology of hepatitis C virus (HCV) infection: the role of CD4 T cells in HCV infection.

Hepatitis C virus (HCV) is yet another example of a pathogen that persists in the presence of a readily apparent immune response. As evidence for both humoral and cellular immune responsiveness is quite strong, our studies have begun to examine whether qualitative defects in CD4 T-cell responses to viral antigens may help to explain why HCV is not eliminated in the vast majority of infections. Direct evidence that CD4 T cells play a role in HCV persistence is lacking, but several observations are consistent with this possibility. Importantly, it does not exclude the role of antibody or killer T cells in the immunopathogenesis of HCV infection. In addition, we discuss the consequences of viral mutation and how naturally occurring variants in immunodominant viral epitopes can effectively suppress helper T-cell responses to wild type virus.

In vitro human Th-cell responses to a recombinant hepatitis C virus antigen: failure in IL-2 production despite proliferation.

Hepatitis C Virus (HCV) causes chronic infection in 80-90% of those exposed and persists despite evidence of immune recognition. To understand the immunological basis of this phenomenon, we have synthesized a non structural (NS) protein that is critical to HCV infection and replication, NS3, and used it to study in vitro helper T-cell responses from infected individuals. Strong proliferative responses were generated by peripheral T-cells isolated from a subset of chronically infected patients, but not by normal, non-infected controls. Interestingly, though gamma-interferon (gammaIfn) and IL-10 were both secreted in response to stimulation by NS3 antigen, IL-2 was not. In contrast, IL-2 was secreted in response to influenza virus vaccine antigen. Lack of IL-2 induction was confirmed by a failure to amplify IL-2 mRNA upon NS3 antigen stimulation, whereas IL-4, IL-15, and gammaIfn mRNA were seen as early as 24 h. The predominance of IL-4 and IL-10 and the lack of IL-2 suggests that in vitro responses to at least some HCV antigens are biased towards a Th2 phenotype, which may be conducive to viral persistence.

Identification of antigenic escape variants in an immunodominant epitope of hepatitis C virus.

Numerous investigators have postulated that one mechanism by which hepatitis C virus (HCV) may evade the immune system is through the formation of escape mutants. This hypothesis is based largely on the observed mutability of the viral genome resulting in evolution of diverse quasispecies over the course of infection. That such diversification is a product of viral RNA polymerase infidelity, immune-driven selection or a combination of the two processes has not been addressed. We have examined sequence variability in a specific segment of HCV RNA encoding a known immunodominant region of the viral helicase, amino acids 358-375 of the non-structural 3 protein. Using sequence-specific oligonucleotide probe hybridization and automated DNA sequencing, we report a high frequency of mutations, essentially all of which result in amino acid replacements. To assess the biological impact of such mutations, corresponding chemically synthesized peptides were compared to wild-type peptide in T cell proliferation assays. We observed that a sizeable fraction of such peptides stimulated attenuated or negligible levels of proliferation by peripheral T cells from a chronically infected patient. This observation is consistent with expectations for immune-mediated selection of escape variants at the epitope level. We postulate that such a mechanism may be important in the immunopathogenesis of HCV infections.

Functionally distinct T-cell epitopes within the hepatitis C virus non-structural 3 protein.

Clearance of Hepatitis C Virus (HCV) infection is an uncommon phenomenon. To understand the mechanism of viral persistence despite active cellular and humoral responses, we examined the in vitro cytokine response of PBMC from an HCV sero-positive, asymptomatic individual to recombinant intact antigen and sixty-nine overlapping peptides of the HCV non-structural (NS) 3 protein. Whereas, intact antigen induced strong proliferation and significant levels of gammaIFN and IL-10, little or no IL-2 was produced. Only 7% of peptides induced IL-2, which also coincided with their ability to stimulate proliferation. In contrast, 38% of the peptides induced gammaIFN while 35% induced IL-10. All IL-2 stimulating peptides also induced significant levels of gammaIFN and among these, a peptide corresponding to residues 358-375 was the strongest. In addition, 16% of the peptides induced both gammaIFN and IL-10. Exogenous recombinant IL-10 inhibited proliferation and IL-2 induction in response to peptide 358-375. Furthermore, neutralization of IL-10 with an anti-IL-10 antibody resulted in enhanced IL-2 production in response to recombinant NS3 protein. We suggest that IL-10 inducing epitopes within HCV NS3 may thus down-regulate IL-2 dependent T-cell responses.

Effect of morphine on interleukin-1 and tumor necrosis factor alpha production from mouse peritoneal macrophages in vitro.

AIM: To study the influence of morphine on lymphokine production from mouse peritoneal macrophages (PM phi). METHODS: The productions of interleukin-1 (IL-1) and tumor necrosis factor (TNF-alpha) from PM phi under various concentrations of morphine with or without naloxone were measured by testing thymocyte proliferation and L929 cell lysis in vitro. RESULTS: Both morphine (1 x 10(-8) - 1 x 10(-3) mol L-1) and naloxone (50 mumol L-1) inhibited IL-1 production from mouse PM phi primed by sodium thioglycolate. Naloxone did not block the inhibitory effect of morphine. TNF-alpha production from PM phi was inhibited by only high concentration (1 mmol L-1) of morphine which was not blocked by naloxone. CONCLUSION: Morphine had a direct inhibitory effect on PM phi, which was not mediated by opioid receptor of PM phi.

Effects of morphine and naloxone on proliferation of lymphocytes in vitro.

AIM: To study the effects of morphine on different lymphocytes and the influence of naloxone. METHODS: The proliferation rates of unmature, resting, and activated T-lymphocytes and B-lymphocytes were determined under various concentrations of morphine with or without naloxone in vitro. RESULTS: Morphine 1 x 10(-10)-1 x 10(-6) mol L-1 enhanced concanavalin A (Con A)-induced splenic T-cell proliferation, and 1 mumol L-1 enhanced lipopolysaccharide (LPS)-induced splenic B-cell proliferation. Naloxone, which per se enhanced the T-cell proliferation, blocked the enhancing effects of morphine. Morphine (1 x 10(-10)-1 x 10(-5) mol L-1) had no influence on the proliferation of resting splenocytes and Con A-induced thymus cells. Morphine 1 mmol L-1 inhibited the proliferation of resting, LPS-induced splenocytes, and Con A-induced splenic and thymus cells. These inhibiting effects were not blocked by naloxone (50 mumol L-1). CONCLUSION: Stimulating effect of morphine on activated T- and B-cells were mediated by opioid receptors and different opioid receptors existed during the differentiation and activation of lymphocytes. The inhibitory effects of morphine (1 mmol L-1) were not mediated by opioid receptors.

Immunomodulating effects of morphine microinjected into periaqueductal gray.

AIM: To study the effects of morphine on immune system through rat brain periaqueductal gray (PAG). METHODS: Three hours after microinjection of morphine through the implanted steel tubes to PAG, splenic cytokines interleukin 2 (IL-2), interleukin 6 (IL-6), tumor necrosis factor (TNF), and natural killer cells (NK) activity were measured. RESULTS: Microinjection of morphine (0.5 microL, 3672 ng) into PAG region had no influence on IL-6 and TNF-alpha (production of splenic macrophages, suppressed the natural killer cell (NK) activity and enhanced T-lymphocyte functions, including concanavalin A (Con A)-induced T-cell proliferation, IL-2 and TNF-beta production. Both the suppressive and stimulating actions were blocked by PAG preinjection of the mu opioid receptor antagonist naloxone (0.5 microL, 1 microgram), which alone showed the contrary effect to morphine. CONCLUSION: Morphine affected immunofunctions through opioid receptors in PAG, and the influences on various immunocompetent cells were different.

Histocompatibility antigens associated with Behçet's disease in northern Han Chinese.

Among Han nationality Chinese and living in the northern area of the Yellow River, 120 patients suffering from Behçet's disease and 100 unrelated healthy individuals were typed for histocompatibility antigens (HLA)-A, -B, -C, and -DR and -DQ antigens. HLA-DR and DQ typing was performed on B-lymphocyte separated with Lympho-B-Kwik. The HLA-antisera were provided by 11th IHWC. Bf alleles and C4 allotypes were determined by immunofixation agarose-gel electrophoresis. HLA-B51 was found in 67/120 (55.83%) patients and in 12/100 (12%) controls, the Chi-square and relative risk values were 45.54 and 9.27, respectively (p < 0.0005). C4AQ0 frequency was significantly increased in the patient group. In the complete form group HLA-B51 was observed more frequently (62.79%). No significant differences of other HLA antigens, frequencies, Bf or B4 alleles were found between the groups.

Long term treatment of Graves' hyperthyroidism with sodium ipodate.

To investigate the long term usefulness of sodium ipodate (Oragrafin) in the management of Graves' hyperthyroidism, we studied the effects of ipodate (500 mg, orally, daily for 23-31 weeks) on serum T3, T4, rT3, and some clinical parameters in five newly diagnosed Graves' hyperthyroid patients. Mean pretreatment serum T3, T4, and rT3 concentrations were 780 ng/dl, 25.4 micrograms/dl, and 118 ng/dl, respectively. One day after the first dose of ipodate, serum T3 decreased by 62% (P less than 0.01), and it was within the normal range thereafter throughout treatment. The serum T4 concentration decreased by 20% (P = 0.09) at 24 h and by 43% (P less than 0.05) at 14 days. Subsequently, serum T4 was 41-65% lower than before treatment throughout the study; rT3 increased 24 h after the first dose of ipodate (118% above baseline; P = 0.1), remained elevated (97-109%) for 10 weeks, and then gradually decreased to the pretreatment level. A marked gain in body weight [5.1 +/- 1.1 (+/- SEM) kg] occurred in all patients. After discontinuation of ipodate, mean thyroid radioiodine (RAI) uptake values increased serially in four patients and were similar to pretreatment values: pretreatment, 74 +/- 6% (+/- SEM); after 7 days, 66 +/- 8%; after 14 days, 71 +/- 7%; after 28 days, 69 +/- 7%. The fifth patients's RAI uptake was 12-16% (vs. a pretreatment value of 48%) from 7-28 days after the end of a 31-week course of ipodate. He remained euthyroid without further treatment for the subsequent 4 months. We conclude that 1) ipodate (500 mg daily) reduces serum T4 and T3 levels as fast and as much as does the 1-g daily dose studied previously; 2) long term use (for 23-31 weeks) of ipodate for the treatment of Graves' hyperthyroidism is clinically feasible; no adverse effects occurred during or after ipodate treatment; and 3) RAI uptake returns to pretreatment levels as early as 7 days after the discontinuation of ipodate. Hence, use of ipodate does not prevent use of 131I therapy for those patients for whom it is otherwise desirable.