A systematic review and meta-analysis on the prevalence of stigma in infectious diseases, including COVID-19: a call to action.

Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.

Lung CD103+dendritic cells and Clec9a signaling are required for neonatal hyperoxia-induced inflammatory responses to rhinovirus infection.

Premature infants, especially those with bronchopulmonary dysplasia (BPD), develop recurrent severe respiratory viral illnesses. We have shown that hyperoxic exposure of immature mice, a model of BPD, increases lung IL-12-producing Clec9a+ CD103+ dendritic cells (DCs), pro-inflammatory responses, and airway hyperreactivity following rhinovirus (RV) infection. However, the requirement for CD103+ DCs and Clec9a, a DAMP receptor that binds necrotic cell cytoskeletal filamentous actin (F-actin), for RV-induced inflammatory responses has not been demonstrated. To test this, 2-day-old C57BL/6J, CD103+ DC-deficient Batf3-/- or Clec9agfp-/- mice were exposed to normoxia or hyperoxia for 14 days. Also, selected mice were treated with neutralizing antibody against CD103. Immediately after hyperoxia, the mice were inoculated with RV intranasally. We found that compared with wild-type mice, hyperoxia-exposed Batf3-/- mice showed reduced levels of IL-12p40, IFN-γ, and TNF-α, fewer IFN-γ-producing CD4+ T cells, and decreased airway responsiveness following RV infection. Similar effects were observed in anti-CD103-treated and Clec9agfp-/- mice. Furthermore, hyperoxia increased airway dead cell number and extracellular F-actin levels. Finally, studies in preterm infants with respiratory distress syndrome showed that tracheal aspirate CLEC9A expression positively correlated with IL12B expression, consistent with the notion that CLEC9A+ cells are responsible for IL-12 production in humans as well as mice. We conclude that CD103+ DCs and Clec9a are required for hyperoxia-induced pro-inflammatory responses to RV infection. In premature infants, Clec9a-mediated activation of CD103+ DCs may promote pro-inflammatory responses to viral infection, thereby driving respiratory morbidity.

Career choice and influential factors among medical students majoring in psychiatry in China.

BACKGROUND: The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors. METHOD: This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students' choices of psychiatry at matriculation and as a career. RESULTS: 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87-2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28-3.08), being female (OR = 1.50, 95% CI = 1.30-1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28-1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08-1.46) correlated positively with students' choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29-0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63-0.97) were less likely to choose psychiatry as a career. CONCLUSION: More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students' interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students' attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.

The Value of 99mTc-PSMA SPECT/CT-Guided Surgery for Identifying and Locating Lymph Node Metastasis in Prostate Cancer Patients.

BACKGROUND: This study evaluated the effect of technetium-99m (99mTc)-labeled prostate-specific membrane antigen (PSMA)-based image-guided surgery on the oncologic outcomes for patients with primary or recurrent prostate cancer (PCa). METHODS: This study retrospectively analyzed 54 consecutive patients with PCa who underwent 99mTc-labeled PSMA-based image-guided surgery between January 2016 and September 2017. These patients received a radical prostatectomy (RP) with pelvic lymph node dissection (PLND) or salvage lymph node dissection (sLND). The resected specimens were compared with findings of postoperative histologic analysis. The responses to the treatment were recorded during the follow-up period. RESULTS: In 31 patients, PSMA single-photon emission computerized tomography (SPECT) and computed tomography (CT) could find 52 suspicious lymph node metastases (LNMs). With the help of PSMA SPECT/CT, 12 patients with recurrence received sLND, 19 primary PCa patients received RP with extended PLND, and 23 primary PCa patients received RP with standard PLND. The findings showed that PSMA SPECT/CT could detect LNMs with high sensitivity and specificity. In six patients, PSMA SPECT/CT could find more LNMs that were not found by MRI and help to modify the extent of lymphadenectomy. At the latest follow-up evaluation, 39 patients showed a biochemical response (BR), 9 patients showed a biochemical recurrence (BCR) after BR, and 6 patients never exhibited BR. The patients who received RP with standard PLND or extended PLND had a better prostate-specific antigen (PSA) response than the patients who received sLND. The patients with pelvic LNMs also had a better PSA response than the patients with retroperitoneal LNMs. CONCLUSIONS: This study showed that 99mTc-PSMA SPECT/CT-guided surgery can remove more LNMs than conventional imaging with high sensitivity and specificity and delay disease progression in PCa patients.

Pulmonary Toxicity in Rats Caused by Exposure to Intratracheal Instillation of SiO2 Nanoparticles.

OBJECTIVE: The effect of the silica nanoparticles (SNs) on lungs injury in rats was investigated to evaluate the toxicity and possible mechanisms for SNs. METHODS: Male Wistar rats were instilled intratracheally with 1 mL of saline containing 6.25, 12.5, and 25.0 mg of SNs or 25.0 mg of microscale SiO2 particles suspensions for 30 d, were then sacrificed. Histopathological and ultrastructural change in lungs, and chemical components in the urine excretions were investigated by light microscope, TEM and EDS. MDA, NO and hydroxyproline (Hyp) in lung homogenates were quantified by spectrophotometry. Contents of TNF-α, TGF-ß1, IL-1ß, and MMP-2 in lung tissue were determined by immunohistochemistry staining. RESULTS: There is massive excretion of Si substance in urine. The SNs lead pulmonary lesions of rise in lung/body coefficients, lung inflammation, damaged alveoli, granuloma nodules formation, and collagen metabolized perturbation, and lung tissue damage is milder than those of microscale SiO2 particles. The SNs also cause increase lipid peroxidation and high expression of cytokines. CONCLUSION: The SNs result into pulmonary fibrosis by means of increase lipid peroxidation and high expression of cytokines. Milder effect of the SNs on pulmonary fibrosis comparing to microscale SiO2 particles is contributed to its elimination from urine due to their ultrafine particle size.

Monitoring Apoptosis of Breast Cancer Xenograft After Paclitaxel Treatment With 99mTc-Labeled Duramycin SPECT/CT.

Our goal was to validate the feasibility of(99m)Tc-duramycin as a potential apoptosis probe for monitoring tumor response to paclitaxel in breast cancer xenografts. The binding of(99m)Tc-duramycin to phosphatidylethanolamine was validated in vitro using paclitaxel-treated human breast carcinoma MDA-MB-231 cells. Female BALB/c mice (n = 5) bearing breast cancer xenografts were randomized into 2 groups and intraperitoneally injected with 40 mg/kg paclitaxel or phosphate-buffered saline.(99m)Tc-duramycin (37-55.5 MBq) was injected at 72 hours posttreatment, and single-photon emission computed tomography/computed tomography was performed at 2 hours postinjection. Apoptotic cells and activated caspase 3 in explanted tumor tissue were measured by flow cytometry. Cellular ultrastructural changes were assessed by light and transmission electron microscopy.(99m)Tc-duramycin with radiochemical purity of >90% exhibited rapid blood clearance and predominantly renal clearance. The tumor-to-muscle ratio in the paclitaxel-treated group (5.29 ± 0.62) was significantly higher than that in the control. Tumor volume was decreased dramatically, whereas tumor uptake of(99m)Tc-duramycin (ex vivo) significantly increased following paclitaxel treatment, which was consistent with apoptotic index, histological findings, and ultrastructural changes. Our data demonstrated the feasibility of(99m)Tc-duramycin for early detection of apoptosis after paclitaxel chemotherapy in breast carcinoma xenografts.

Pim-3 contributes to radioresistance through regulation of the cell cycle and DNA damage repair in pancreatic cancer cells.

Resistance of cancer cells to chemoradiotherapy is a major clinical problem in pancreatic cancer treatment. Therefore, understanding the molecular basis of cellular resistance and identifying novel targets are essential for improving treatment efficacy for pancreatic cancer patients. Previous studies have demonstrated a significant role for Pim-3 in pancreatic cancer survival against gemcitabine-induced genotoxic stress. Here, we observed that radiation treatment enhanced Pim-3 expression in human pancreatic cancer cells in vitro. Stable overexpression of Pim-3 in pancreatic cancer cells significantly protected cells against radiation treatment by attenuating G2/M phase cell cycle arrest and DNA damage response. Silencing of Pim-3 expression significantly elevated the phosphorylation of histone variant H2AX, a marker of DNA double strand breaks, and decreased the activation of ataxia-telangiectasia-mutated (ATM) kinase, along with its downstream targets, eventually enhancing the radiosensitivity of human pancreatic cancer cells in vitro and in vivo. Hence, we demonstrated a novel function for Pim-3 in human pancreatic cancer cell survival against radiation. Targeting Pim-3 may be a promising way to improve treatment efficacy in combination with radiotherapy in human pancreatic cancer.

Metabolic tumour burden assessed by ¹8F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection.

PURPOSE: Tumour burden is one of the most important prognosticators for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the predictive significance of metabolic tumour burden measured by (18)F-FDG PET/CT in patients with resectable PDAC. METHODS: Included in the study were 122 PDAC patients who received preoperative (18)F-FDG PET/CT examination and radical pancreatectomy. Metabolic tumour burden in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), pathological tumour burden (tumour size), serum tumour burden (baseline serum CA19-9 level), and metabolic activity (maximum standard uptake value, SUVmax) were determined, and compared for their performance in predicting overall survival (OS) and recurrence-free survival (RFS). RESULTS: MTV and TLG were significantly associated with baseline serum CA19-9 level (P = 0.001 for MTV, P < 0.001 for TLG) and tumour size (P < 0.001 for MTV, P = 0.001 for TLG). Multivariate analysis showed that MTV, TLG and baseline serum CA19-9 level as either categorical or continuous variables, but not tumour size or SUVmax, were independent risk predictors for both OS and RFS. Time-dependent receiving operating characteristics analysis further indicated that better predictive performances for OS and RFS were achieved by MTV and TLG compared to baseline serum CA19-9 level, SUVmax and tumour size (P < 0.001 for all). CONCLUSION: MTV and TLG showed strong consistency with baseline serum CA19-9 level in better predicting OS and RFS, and might serve as surrogate markers for prediction of outcome in patients with resectable PDAC.

Effects of 5-amino salicylic acid on the expression of multidrug resistance gene in ulcerative colitis.

BACKGROUND/AIMS: To study the effect of drugs on the expression of multidrug resistance gene in ulcerative colitis. METHODOLOGY: The expressions of multidrug resistance (MDR) 1 gene and its product P-Gp were detected by reverse transcription-polymerase chain reaction and immunohistochemistry to realize the impact of drugs on ulcerative colitis. RESULTS: MDR1 gene and P-Gp did not exhibit significant difference (P > 0.05) before and after amino salicylic acid drug treatment. Compared with the control group, their expressions before treatment in the ineffective corticosteroid- and immunosuppressant-treated groups did not exhibit significant difference (P > 0.05). Their pre- and post-treatment expressions in the ineffective groups were compared with those in the normal control group and in the effective group, and significant differences were observed (P < 0.05). CONCLUSIONS: 5-Amino salicylic acid drugs have little effect on the expression of MDR1 and its product P-Gp. The expressions of MDR1 and P-Gp were much higher in groups that showed ineffectiveness for corticosteroids and immunosuppressants after treatment.

An in vivo molecular imaging probe (18)F-Annexin B1 for apoptosis detection by PET/CT: preparation and preliminary evaluation.

There is an increasing need to develop non-invasive molecular imaging strategies for visualizing and quantifying apoptosis status of diseases (especially for cancer) for diagnosis and monitoring treatment response. Since externalization of phosphatidylserine (PS) is one of the early molecular events during apoptosis, Annexin B1 (AnxB1), a member of Annexins family with high affinity toward the head group of PS, could be a potential positron emission tomography (PET) imaging probe for imaging cell death process after labeled by positron-emitting nuclides, such as (18)F. In the present study, we investigated a novel PET probe, (18)F-labeled Annexin B1 ((18)F-AnxB1), for apoptosis imaging. (18)F-AnxB1 was prepared reliably by conjugating AnxB1 with a (18)F-tag, N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB), in a radiolabeling yield of about 20 % within 40 min. The in vitro binding of (18)F-AnxB1 with apoptotic cells induced by anti-Fas antibody showed twofold increase compared to those without treatment, confirmed by flow cytometric analysis with AnxV-FITC/PI staining. Stability tests demonstrated (18)F-AnxB1 was rather stable in vitro and in vivo without degradation. The serial (18)F-AnxB1 PET/CT scans in healthy rats outlined its biodistribution and pharmacokinetics, indicating a rapid renal clearance and predominant accumulation into kidney and bladder at 2 h p.i. (18)F-AnxB1 PET/CT imaging was successfully applied to visualize in vivo apoptosis sites in tumor induced by chemotherapy and in kidney simulated by ischemia-reperfusion injury. The high-contrast images were obtained at 2 h p.i. to delineate apoptotic tumor. Apoptotic region could be still identified by (18)F-AnxB1 PET 4 h p.i., despite the high probe retention in kidneys. In summary, we have developed (18)F-AnxB1 as a PS-specific PET probe for the apoptosis detection and quantification which could have broad applications from disease diagnosis to treatment monitoring, especially in the cases of cancer.

The maximum standardized uptake value of 18 F-FDG PET scan to determine prognosis of hormone-receptor positive metastatic breast cancer.

BACKGROUND: Whether PET scan maximum standard uptake value (SUVmax) could differentiate luminal A from luminal B and help predict the survival of metastatic breast cancer (MBC) patients with luminal subtype is still unknown and need to be investigated. METHODS: 305 MBC patients with luminal subtypes were screened with PET/CT. Eligible patients were prospectively followed up. RESULTS: In total, 134 patients were eligible for this study. SUVmax was significantly related to the number of metastatic sites and presence of visceral metastasis on univariate analysis. SUVmax could not effectively differentiate patients with luminal A from luminal B subtype. Although luminal subtype at diagnosis could predict the relapse-free interval, it could not predict progression-free survival (PFS) or overall survival (OS) after developing relapse. In contrast, SUVmax was predictive of both PFS and OS and this effect was maintained in multivariate COX regression model. CONCLUSIONS: SUVmax of MBC did not correlate with molecular subtypes of primary tumor. While molecular subtype may be a valuable prognostic factor at primary diagnosis of breast cancer, the SUVmax, rather than molecular subtype, does have a potential to predict independently in multivariate analysis for the PFS and OS in patients with metastatic disease of luminal subtype.

[Expression of Galectins in umbilical cord mesenchymal stem cells].

OBJECTIVE: To investigate the expression of Galectins in umbilical cord mesenchymal stem cells (UC-MSCs) from Wharton's jelly. METHODS: Umbilical cords were obtained sterilely from full term caesarean infants, then mesenchymal stem cells (MSCs) were isolated from Wharton's jelly of the umbilical cord via tissue cultivation. The morphology of UC-MSCs was observed under the optical microscope, and its immunophenotypes were analyzed by flow cytometry. The differentiation of UC-MSCs into the osteoblasts and adipocytes was determined utilizing von Kossa calcium node staining and oil red O staining, respectively. The expression of Galectins at mRNA level was measured by RT-PCR. The levels of secretory Galectin-3 in culture supernatants were detected by sandwich enzyme-linked immunosorbent assay. RESULTS: The UC-MSCs could be generated by tissue cultivation. Flow cytometry showed they highly expressed membrane molecules, such as CD29, CD44, CD73, CD90 and CD105, but did not express hematopoietic specific markers (CD14, CD34, and CD45) and immune rejection related molecule HLA-DR. UC-MSCs could differentiate into osteoblasts or adipocytes under appropriate experimental conditions. At the mRNA level, Galectin-1, 3, 4, 8 and 9 were detected in UC-MSCs. And they also could secrete soluble Galectin-3 in a cell number dependent manner. Statistical differences were obtained among the different cell number incubation groups (F=16.901,P=0.002). However, the secretory manner of Galectin-3 was not time dependent. CONCLUSION: UC-MSCs, derived from Wharton's jelly, were successfully cultured via tissue cultivation, and they could express secretory Galectin-3. All these data laid the foundation for further detecting the immunomodulatory mechanism of UC-MSCs.

IL-17a-producing γδT cells and NKG2D signaling mediate bacterial endotoxin-induced neonatal lung injury: implications for bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in preterm birth survivors characterized by inflammation, impaired alveolarization and dysmorphic vasculature. Activated IL-17A+ lymphocytes are key drivers of inflammation in preterm infants. We have shown that in immature mice chronic airway exposure to lipopolysaccharide (LPS) induces pulmonary inflammation, increased IL-17a expression, and hypoalveolarization, a BPD-like phenotype. The source of IL-17a and contribution to lung pathology is unknown. The natural-killer group 2, member D (NKG2D) receptor mediates activation and IL-17a production in γδ T cells by binding to stress molecules. LPS induces NKG2D ligand expression, including Rae-1 and MULT1. We hypothesized that IL-17a+ γδ T cells and NKG2D signaling mediate neonatal LPS-induced lung injury. Immature C57BL/6J (wild type), Nkg2d-/- or Tcrd-/- (lacking γδ T cells) mice were inoculated with 3ug/10ul of LPS from E. coli O26:B6 or 10ul of PBS intranasally on day of life 3, 5, 7, and 10. Selected mice were treated with neutralizing antibodies against IL-17a, or NKG2D intraperitoneally. Lung immune cells were assessed by flow cytometry and gene expression was analyzed by qPCR. Alveolar growth was assessed by lung morphometry. We established that anti-IL-17a antibody treatment attenuated LPS-induced hypoalveolarization. We found that LPS induced the fraction of IL-17a+NKG2D+ γδ T cells, a major source of IL-17a in the neonatal lung. LPS also induced lung mRNA expression of NKG2D, Rae-1, MULT1, and the DNA damage regulator p53. Anti-NKG2D treatment attenuated the effect of LPS on γδ T cell IL-17a expression, immune cell infiltration and hypoalveolarization. LPS-induced hypoalveolarization was also attenuated in Nkg2d-/- and Tcrd-/- mice. In tracheal aspirates of preterm infants IL-17A and its upstream regulator IL-23 were higher in infants who later developed BPD. Also, human ligands of NKG2D, MICA and MICB were present in the aspirates and MICA correlated with median FiO2. Our novel findings demonstrate a central role for activated IL-17a+ γδ T cells and NKG2D signaling in neonatal LPS-induced lung injury. Future studies will determine the role of NKG2D ligands and effectors, other NKG2D+ cells in early-life endotoxin-induced lung injury and inflammation with a long-term goal to understand how inflammation contributes to BPD pathogenesis.

Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease.

The purpose of this study was to examine the characteristics of proximal and distal gastroesophageal reflux in patients with gastroesophageal reflux disorder and analyze their clinical symptoms. A total of 67 patients with typical esophageal symptoms were selected for this study. All participants completed the reflux disease questionnaire and a questionnaire survey of extraesophageal symptoms. Diagnosis was made using a 24-h impedance-pH detection and proton pump inhibitor. The results showed that the proximal reflux group had a higher number of acid reflux episodes compared to the distal reflux group (P < 0.05). Similarly, the proximal reflux group also had a higher number of gas reflux episodes compared to the distal reflux group (P < 0.05). On the other hand, the distal reflux group had a higher number of mixed reflux episodes compared to the proximal reflux group (P < 0.05). These differences were statistically significant. This study revealed that acid reflux and gas reflux were more predominant in the proximal reflux group, while mixed reflux was more predominant in the distal reflux group.

Early-life hyperoxia-induced Flt3L drives neonatal lung dendritic cell expansion and proinflammatory responses.

Premature infants with chronic lung disease, bronchopulmonary dysplasia (BPD), develop recurrent cough and wheezing following respiratory viral infections. The mechanisms driving the chronic respiratory symptoms are ill-defined. We have shown that hyperoxic exposure of neonatal mice (a model of BPD) increases the activated lung CD103+ dendritic cells (DCs) and these DCs are required for exaggerated proinflammatory responses to rhinovirus (RV) infection. Since CD103+ DC are essential for specific antiviral responses and their development depends on the growth factor Flt3L, we hypothesized that early-life hyperoxia stimulates Flt3L expression leading to expansion and activation of lung CD103+ DCs and this mediates inflammation. We found that hyperoxia numerically increased and induced proinflammatory transcriptional signatures in neonatal lung CD103+ DCs, as well as CD11bhi DCs. Hyperoxia also increased Flt3L expression. Anti-Flt3L antibody blocked CD103+ DC development in normoxic and hyperoxic conditions, and while it did not affect the baseline number of CD11bhi DCs, it neutralized the effect of hyperoxia on these cells. Anti-Flt3L also inhibited hyperoxia-induced proinflammatory responses to RV. In tracheal aspirates from preterm infants mechanically-ventilated for respiratory distress in the first week of life levels of FLT3L, IL-12p40, IL-12p70 and IFN-γ were higher in infants who went on to develop BPD and FLT3L levels positively correlated with proinflammatory cytokines levels. This work highlights the priming effect of early-life hyperoxia on lung DC development and function and the contribution of Flt3L in driving these effects.

Calcified metastases from ovarian carcinoma highlighted by F-18 FDG PET/CT: report of two cases.

Two cases of postoperative female patients with ovarian serous papillary carcinoma were referred for F-18 Fluorodeoxyglucose (F-18 FDG) PET/CT to evaluate suspicious recurrence and/or metastasis. One patient presented with multiple extensive calcified lesions with increased FDG uptake in the abdominopelvic cavity and the series of PET/CT scans showed progression of disease after chemotherapy. The other patient presented with three calcified masses with intensive uptake of FDG located in the left pelvis, the right subphrenic region, and the right supradiaphragmatic area, respectively. These suggest that F-18 FDG PET/CT can be useful in identifying malignant calcification and assessing therapeutic response of calcified malignancy.

[A case report of IgG4-related sclerosing disease with lung involvement].

IgG4-related sclerosing disease(IgG4-RSD) is a kind of lymphoplasmacytic disease with multi-organ involvement and is characterized by serum IgG4 elevation and tissue IgG4 positive plasma cell infiltration. Autoimmune pancreatitis, sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis and lymphadenopathy make up its main clinical manifestations. This difficult case was a middle-aged female with onset as muiltiple lymph nodes and glands enlargement, including lacrimal gland, salivary glands and pancreas. Meanwhile, repeated examinations of auto-antibodies and serum IgG4 were all negative. The patient didn't respond well to glucocorticoid therapy, and further progressed to rare lung involvement presenting as lung nodule. This complex entity was eventually diagnosed as IgG4-RSD by the support of histopathology evidence of IgG4 immunohistochemistry stain. Though IgG4-RSD has been known for years, it is still underappreciated in China and case reports are scarce. The case report here with literature review is just to enhance the recognition of this disease regarding its pathogenesis, various clinical manifestations, diagnosis and therapy.

Gelsolin Attenuates Neonatal Hyperoxia-Induced Inflammatory Responses to Rhinovirus Infection and Preserves Alveolarization.

Prematurity and bronchopulmonary dysplasia (BPD) increase the risk of asthma later in life. Supplemental oxygen therapy is a risk factor for chronic respiratory symptoms in infants with BPD. Hyperoxia induces cell injury and release of damage-associated molecular patterns (DAMPs). Cytoskeletal filamentous actin (F-actin) is a DAMP which binds Clec9a, a C-type lectin selectively expressed on CD103+ dendritic cells (DCs). Co-stimulation of Clec9a and TLR3 induces maximal proinflammatory responses. We have shown that neonatal hyperoxia (a model of BPD) increases lung IL-12+Clec9a+CD103+ DCs, pro-inflammatory responses and airway hyperreactivity following rhinovirus (RV) infection. CD103+ DCs and Clec9a are required for these responses. Hyperoxia increases F-actin levels in bronchoalveolar lavage fluid (BALF). We hypothesized that the F-actin severing protein gelsolin attenuates neonatal hyperoxia-induced Clec9a+CD103+ DC-dependent pro-inflammatory responses to RV and preserves alveolarization. We exposed neonatal mice to hyperoxia and treated them with gelsolin intranasally. Subsequently we inoculated the mice with RV intranasally. Alternatively, we inoculated normoxic neonatal mice with BALF from hyperoxia-exposed mice (hyperoxic BALF), RV and gelsolin. We analyzed lung gene expression two days after RV infection. For in vitro studies, lung CD11c+ cells were isolated from C57BL/6J or Clec9agfp-/- mice and incubated with hyperoxic BALF and RV. Cells were analyzed by flow cytometry. In neonatal mice, gelsolin blocked hyperoxia-induced Il12p40, TNF-α and IFN-γ mRNA and protein expression in response to RV infection. Similar effects were observed when gelsolin was co-administered with hyperoxic BALF and RV. Gelsolin decreased F-actin levels in hyperoxic BALF in vitro and inhibited hyperoxia-induced D103lo DC expansion and inflammation in vivo. Gelsolin also attenuated hyperoxia-induced hypoalveolarization. Further, incubation of lung CD11c+ cells from WT and Clec9agfp-/- mice with hyperoxic BALF and RV, showed Clec9a is required for maximal hyperoxic BALF and RV induced IL-12 expression in CD103+ DCs. Finally, in tracheal aspirates from mechanically ventilated human preterm infants the F-actin to gelsolin ratio positively correlates with FiO2, and gelsolin levels decrease during the first two weeks of mechanical ventilation. Collectively, our findings demonstrate a promising role for gelsolin, administered by inhalation into the airway to treat RV-induced exacerbations of BPD and prevent chronic lung disease.

Comparison of effects of aminosalicylic acid, glucocorticoids and immunosuppressive agents on the expression of multidrug-resistant genes in ulcerative colitis.

To compare the effects of aminosalicylic acid, glucocorticoids and immunosuppressants on the expression levels of multidrug resistance genes in patients with ulcerative colitis (UC), with the aim of providing a theoretical and therapeutic basis for the diagnosis, treatment, and prevention of UC. Fresh colonic mucosal tissues or postoperative pathological biopsies from 148 UC patients were collected, and the distribution sites and morphology of P-glycoprotein (P-gp) were detected using immunohistochemical staining. RT-PCR was used to quantify the expression levels of multidrug resistance gene (MDR1) mRNA before and after the corresponding treatment, and the effects of aminosalicylic acid, glucocorticoids and immunosuppressive drugs on P-gp were compared. In addition, the effects of the three drugs on MDR1 mRNA were analyzed. Administration of 5-aminosalicylic acid (5-ASA) drugs did not correlate with MDR1 expression in UC, whereas administration of glucocorticoids and immunosuppressive drugs was positively correlated with MDR1 expression profile. The expression levels of MDR1 mRNA and its product P-gp were significantly upregulated in patients who did not respond to glucocorticoids and immunosuppressive drugs. 5-ASA had no effect on the expression levels of MDR1 and its product P-gp in patients with a confirmed diagnosis of UC. However, the use of glucocorticoids and immunosuppressants can increase the expression level of MDR1.

The role of technetium-99m methoxyisobutyl isonitrile scintigraphy in predicting the therapeutic effect of chemotherapy against nasopharyngeal carcinoma.

BACKGROUND: The authors prospectively evaluated the correlation between technetium-99m methoxyisobutyl isonitrile ((99m) Tc-MIBI) accumulation in tumors and response to induction chemotherapy in patients with nasopharyngeal carcinoma (NPC). METHODS: Eighty-six patients with locally advanced NPC underwent single-photon emission computed tomography 15 minutes after an intravenous injection of 740 megabecquerels (20 mCi) (99m) Tc-MIBI before chemotherapy. The tumor uptake ratio (TUR) was calculated. Two weeks after the second cycle of combined chemotherapy with 5-fluorouracil (5-FU) and cisplatin (DDP), the tumor response rate was evaluated. The correlation between (99m) Tc-MIBI accumulation in tumors and response to chemotherapy with 5-FU/DDP was examined. RESULTS: Positive accumulation of (99m) Tc-MIBI in tumors was observed in 76 patients (88.4%). The tumor response was a complete response (CR) in 8 patients, a partial response (PR) in 68 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. The response rate (CR and PR) to 5-FU/DDP chemotherapy in patients who had positive (99m) Tc-MIBI accumulation (tumor uptake ratio [TUR] >1.1) was higher than that in patients who had negative (99m) Tc-MIBI accumulation (TUR ≤ 1.1; 98.7% vs 10%; P < .001). CONCLUSIONS: Patients with negative (99m) Tc-MIBI accumulation were resistant to 5-FU/DDP chemotherapy. (99m) Tc-MIBI imaging in patients with NPC was capable of predicting tumor response to chemotherapy with 5-FU/DDP and can help in the selection of patients for induction chemotherapy.