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Plasma cell mastitis (PCM) and granulomatous mastitis (GM) are the most common inflammatory diseases constituting nonbacterial mastitis (NBM). However, the pathogenesis of NBM remains unclear. In this study, risk factors for NBM were assessed, as well as the pathological features of PCM and GM. The levels of C3/C3a-C3aR and C5/C5a-C5aR1 of tissues were detected by IHC and WB. Exosomes were isolated from serum and identified by transmission electron microscopy. Then, C3 and C5 levels were detected in peripheral blood, and exosomes were assessed by flow cytometry and immunoelectron microscopy. Obesity and prolonged lactation were risk factors for NBM. The infiltration of plasma cells and lymphocytes around the dilated catheter in PCM and the formation of granulomatous structures in GM were the respective pathological features. C3/C3a-C3aR and C5/C5a-C5aR1 levels were elevated in PCM and GM tissue samples. There were no differences in peripheral blood levels of C3 and C5, while C3a and C5a were highly expressed in exosomes. These results suggest that the complement family is activated in PCM and GM, exosomes enrich C3a and C5a, and mediate the spread of inflammation. These findings provide new insights into the molecular mechanisms of PCM and GM and identify therapeutic targets.

Plasma cell mastitis (PCM) and granulomatous mastitis (GM) are common inflammatory nonbacterial mastitis (NBM). However, the pathogenesis of NBM is still unclear.Methods. In this study, we statistically analyzed the pathological features of PCM and GM using pathological HE staining and tissue transmission electron microscopy. The levels of MAC (C5b-9n), P-selectin, E-selectin, and ICAM-1 were detected through IHC, WB, ELISA, and qPCR. The expression level and location of MAC were observed by tissue immunological electron microscopy. In addition, exosomes were isolated from tissues, identified using transmission electron microscopy, and the densities were detected by Nano-FCM. Finally, the expression intensity of MAC in exosomes was detected by flow cytometry and immunoelectron microscopy.Results. The damage and apoptosis of mammary duct epithelial cells are the common pathological features of PCM and GM. MAC is primarily located in the cell membrane of mammary ductal epithelial cells and is significantly expressed in PCM and GM. The density of exosomes in PCM and GM tissues was elevated, and MAC was highly expressed in exosomes. In addition, the expression of P-selectin, E-selectin, and ICAM-1 in PCM and GM was significantly higher than in the normal group.Conclusion. We found severe damage of the mammary duct epithelial cells in PCM and GM tissues, which was verified by relevant pathological methods. Earlier studies demonstrated that MAC is highly expressed in PCM and GM tissues and exosomes seem to play a very important role in the understanding of MAC. Furthermore, MAC is involved in inflammatory infiltration and lesion of mammary duct epithelial cells upregulated by P-selectin, E-selectin, and ICAM-1. These findings provide new insights into PCM and GM molecular mechanisms with novel therapeutic advances.

Background Postoperative delirium is a common psychiatric disorder among patients who undergo spinal surgery. The purpose of current meta-analysis was to assess the potential risk factors related to delirium in spinal surgery. Methods We searched the following databases: PubMed, EMBASE, the Cochrane Library, and Web of Science, from inception to July 2020. Two reviewers independently assessed the quality of the included studies using the previously described Newcastle-Ottawa Scale (NOS). We included spinal surgery patients who suffered with delirium or not. Stata 12.0 was used for meta-analysis. Results Thirteen trial studies that met our inclusion criteria were incorporated into the meta-analysis. Postoperative delirium was associated with an increase of the duration of hospital stay (P = 0.044) and increased perioperative readmission rate (P = 0.013) and economic costs (P = 0.002). This meta-analysis demonstrates that there were twenty-two risk factors: general characteristic: old age, female patients, history of surgery, diabetes mellitus, hypertension; preoperative data: low hematocrit, low hemoglobin, low albumin, low sodium, depression; operative data: operating time, total blood loss; postoperative data: low sodium, low hemoglobin, low hematocrit, low albumin, fever, low potassium, blood sugar, and visual analog scale (VAS). Conclusions Delirium not only prolongs the length of hospital stay, but also increases readmission rate and the economic costs. Several risk factors including old age, female patients, history of surgery, diabetes mellitus, low hematocrit, low hemoglobin, low albumin, low sodium, depression; operative data: operating time, total blood loss, low sodium, low hemoglobin, low hematocrit, low albumin, fever, low potassium, blood sugar, and VAS were significant predictors for postoperative delirium after spinal surgery.

Background. China has experienced rapid urbanization in the past 30 years. We aimed to report blood cadmium level (BCL) in the rapidly urbanized Yangtze Plain of China, and explore the association between BCL and 25-hydroxyvitamin D (25(OH)D). Methods. Our data source was the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cross-sectional study (ChiCTR-ECS-14005052, www.chictr.org). We enrolled 3234 subjects from 12 villages in the Yangtze Plain. BCLs were measured by atomic absorption spectrometry. 25(OH)D was measured with a chemiluminescence assay. Results. A total of 2560 (79.2%) subjects were diagnosed with vitamin D deficiency. The median (interquartile range) BCL was 1.80 μg/L (0.60–3.42) for men and 1.40 μg/L (0.52–3.10) for women. In women, mean 25(OH)D concentrations were inversely associated with BCL (0.401, 95% confidence interval: –0.697 to –0.105 nmol/L lower with each doubling of the BCL) after adjustment for age, educational status, current smoking, body mass index, diabetes, and season. However, there was no significant difference in 25(OH)D across the BCL tertiles for men. Conclusions. BCL in Chinese residents in the Yangtze Plain were much higher than that in developed countries. An inverse association between BCL and 25(OH)D was found in general Chinese women after multivariable adjustment. Future prospective cohort and animal studies are warranted to resolve the direction and temporality of these relationships, and to elucidate the exact mechanisms involved.

Background Intervertebral disc degeneration (IVDD) is a well-known cause of lower back pain, which is induced by multiple factors including increased apoptosis and decreased survival of nucleus pulposus cells. In this study, we evaluate the effect and potential mechanism of miR-660 on the nucleus pulposus cells apoptosis induced by TNF-α. Methods First, we collected tissue of nucleus pulposus from IVDD and healthy controls. General characteristic of the IVDD and healthy control was also collected. And, we also collected nucleus pulposus cells that stimulated by TNF-α or control. miRNA microarray was performed to identify the differentially expressed miRNAs. Apoptosis rate and miR-660 relative expression was measured after stimulated with different concentration of TNF-α to identify the optimal concentration of TNF-α. Second, we successfully constructed antigomiR-660 to block the miR-660 expression in nucleus pulposus cells and then stimulated with TNF-α (100 ng/ml, 12 h). The apoptosis rates and relative protein expression were then measured again. The target association between miR-660 and SAA1 was confirmed by dual-luciferase reporter. Results There was no significant difference between the age (IVDD: 39 ± 10 years, healthy controls: 36 ± 7 years), BMI and sex between IVDD and healthy controls. Microarray analysis found that miR-660 was significantly up-regulated in IVDD and TNF-α treated groups, which was further identified by PCR. We found that the rate of apoptosis and miR-660 expression increased with TNF-α concentration increased. Finally, TNF-a with 100 ng/ml was used for further experiment. Compared with TNF-α group, TNF-α + antigomiR-660 could significantly down-regulated the apoptosis rate and relative protein (c-Caspase3 and c-Caspase7). Dual-luciferase reporter revealed that miR-660 could directly binding to the SAA1 at 80–87 sites. Compared with TNF-α alone group, TNF-α + antigomiR-660 significantly up-regulated the SAA1 expression (P Conclusion These results indicated that knockdown of miR-660 protected the nucleus pulposus from apoptosis that induced TNF-α via up-regulation of SAA1. Further studies should focus on the role of miR-660 in protecting IVDD in vivo.

Ureteral fibroepithelial polyps (UFPs) are rare benign tumors and ureteroscopy has been used for treatment. We compared the effect of UFP by ureteroscopy combined with holmium laser or thulium laser.Twenty-five patients with UFPs were treated in our hospital between May 2003 and April 2013. All patients received ultrasound check and intravenous urography (IVU). We performed ureteroscopy operation and found ureteral polyps, so we resected the polyps with holmium laser (12 cases) or thulium laser (13 cases). During the 3-year follow-up, all patients received IVU 2 or 3 months after the double-J stent was removed, and ultrasonic checks every 3-6 months after that.All patients had UFPs resected. Three patients in the holmium laser group had ureteral perforation during operation, and four patients in the holmium laser group developed ureterostenosis. No patients in thulium laser group experienced any severe complications during the procedure. Further, during follow-up, there was no indication of an increase of hydronephrosis in any patients. These findings lead to conclude there were no developments of ureterostenosis nor an experience of any reoccurrence in thulium laser group.Ureteroscopy operations, combined with holmium or thulium laser resection, are effective methods for treating UFP, but thulium laser does better in reducing the incidence of ureterostenosis.

The present study retrospectively reviewed the clinical efficacy of open reduction and internal fixation with buttress plates and cannulated screws via a posterolateral approach for the treatment of large posterior malleolus fractures. From July 2009 to April 2012, 34 patients (15 males and 19 females; mean age 41.2 years) with posterior malleolus fractures involving >25% of the distal articular tibia, were treated by cannulated screw and buttress plate fixation. All the patients were followed for ≥24 months. The outcome measures included the radiographic appearance of the reduction and bone union and the Baird-Jackson score. The average operation time was 105.6 (range 78 to 145) minutes. Radiologic examination showed all fractures achieved anatomic reduction and primary bone union at a mean of 3.8 (range 3 to 7) months after surgery. After an average follow-up period of 32.7 (range 24 to 44) months, no displacement, loosening, or breakage of internal fixation was observed. However, mild posttraumatic arthritis was present in 3 patients. According to the Baird-Jackson scoring system, the outcomes were rated as excellent in 11 cases, good in 17, fair in 5, and poor in only 1 case, for an excellent and good rate of 82.3%. An association analysis indicated age and injury mechanism might be factors influencing the intraoperative and postoperative outcomes. A posterolateral approach with buttress plate and cannulated screw internal fixation could be an effective technique for reduction and fixation of large posterior malleolus fragments.

Development of an effective vaccine for severe acute respiratory syndrome (SARS) remains to be a priority to prevent possible re-emergence of SARS coronavirus (SARS-CoV). We previously demonstrated that the receptor-binding domain (RBD) of SARS-CoV S protein is a major target of neutralizing antibodies. This suggests that the RBD may serve as an ideal vaccine candidate. Recombinant adeno-associated virus (rAAV) has been proven to be an effective system for gene delivery and vaccine development. In this study, a novel vaccine against SARS-CoV was developed based on the rAAV delivery system. The gene encoding RBD was cloned into a pAAV-IRES-hrGFP plasmid. The immunogenicity induced by the resulting recombinant RBD-rAAV was evaluated in BALB/c mice. The results demonstrated that (1) a single dose of RBD-rAAV vaccination could induce sufficient neutralizing antibody against SARS-CoV infection; (2) two more repeated doses of the vaccination boosted the neutralizing antibody to about 5 times of the level achieved by a single dose of the immunization and (3) the level of the antibody continued to increase for the entire duration of the experiment of 5.5 months. These results suggested that RBD-rAAV is a promising SARS candidate vaccine.

This study was conducted to evaluate the differential proliferation ability of satellite cells (SCs) derived from pectoral muscles (PM) with different fiber characteristics and further to explore the underlying molecular mechanism. WENS Yellow Feather Chicks (WYFC) were chosen as the animal model, with White Plymouth Rock Chicks (WPRC) as a comparison. The results showed that WPRC had higher body and pectoral muscle weight than WYFC at 4 days old (P 0.05). However, WYFC showed greater fiber numbers/mm(2) but smaller fiber cross-sectional area compared with WPRC in PM (P 0.05). SCs derived from PM of WYFC had a faster proliferation rate but smaller cell size compared with that from PM of WPRC (P 0.05). The percentage of cell population in G2/M phase and the messenger RNA abundance of TSC1 (P = 0.08), Rheb (P = 0.07) and target of rapamycin (TOR, P = 0.06) in WYFC were higher than that in WPRC. In conclusion, our results demonstrated that SCs isolated from PM of WYFC had faster proliferation rate but smaller cell size than that in WPRC. The higher SC proliferation in WYFC may be due to higher gene expression of TOR signaling pathway than in WPRC, and the larger cell size of WPRC may be due to higher insulin-like growth factor-1 expression than in WYFC.

The mortality of human infection by influenza A/H5N1 virus can exceed 80%. The high mortality and its poor response to the neuraminidase inhibitor oseltamivir have been attributed to uncontrolled virus-induced cytokine storm. We challenged BALB/c mice with 1,000 LD 50 of influenza A/Vietnam/1194/04. Survival, body weight, histopathology, inflammatory markers, viral loads, T lymphocyte counts, and neutralizing antibody response were documented in infected mice treated individually or in combination with zanamvir, celecoxib, gemfibrozil, and mesalazine. To imitate the real-life scenario, treatment was initiated at 48 h after viral challenge. There were significant improvements in survival rate ( P = 0.02), survival time ( P < 0.02), and inflammatory markers ( P < 0.01) in the group treated with a triple combination of zanamivir, celecoxib, and mesalazine when compared with zanamivir alone. Zanamivir with or without immunomodulators reduced viral load to a similar extent. Insignificant prolongation of survival was observed when individual agents were used alone. Significantly higher levels of CD4 + and CD8 + T lymphocytes and less pulmonary inflammation were also found in the group receiving triple therapy. Zanamivir alone reduced viral load but not inflammation and mortality. The survival benefits of adding celecoxib and mesalazine to zanamivir could be caused by their synergistic effects in reducing cytokine dysfunction and preventing apoptosis. Combinations of a neuraminidase inhibitor with these immunomodulators should be considered in randomized controlled treatment trials of patients suffering from H5N1 infection.

Since the antiretroviral therapy (ART) was introduced to patients infected by human immunodeficiency virus (HIV), the HIV related mortality and morbidity have been significantly reduced. The major obstacle for long-term successful anti-HIV treatment is the emergence of drug resistant mutants. Current data of drug resistance was mainly obtained on HIV-1 subtype B but rarely on non-B virus, even more rare with newly emerged circulating recombinant forms (CRFs). The lack of such data limits the rational management of ART for the increasing number of patients infected by non-subtype B virus. In this study, a HIV-1 CRF07_BC strain CNGZD was isolated from a HIV patient and its genome was sequenced and deposited in GenBank (JQ423923). Potential drug resistant mutants of this CRF07_BC virus strain were selected in PBMCs cultures in the presence of Nevirapine (NVP), which is the most frequently used antiretroviral drug in China. Four combination profiles of mutations were identified in the NVP-selected mutants, which were initiated with A98G, V108I, Y181C and I135T/I382L and followed by more than two other mutations at the end of the selections, respectively. A total of seven previously reported mutations (A98G, V106M, V108I, I135T, Y181C, V189I, K238N) and seven novel mutations (P4H, T48I, I178M, V314A, I382L/V, T386A) in the reverse transcriptase gene were found in these NVP-selected mutants. Phenotypic analysis in the NVP-selected mutants showed that all the mutations, except P4H, contribute to NVP resistance. Among them, V106M and Y181C reduce NVP susceptibility for more than 20-fold, while the other mutations cause less than 20 folds drug resistance. Although the information obtained in this in vitro selection study may not fully cover resistant mutations which will actually occur in patients, it has still provided useful information for rational management of ART in patients infected with HIV CRF_BC subtype.