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Background: Recurrence and metastasis are the usual manifestations of treatment failure of epithelial ovarian carcinoma (EOC). Vasculogenic mimicry (VM; blood supply development often seen in highly aggressive cancers), aldehyde dehydrogenase 1 (ALDH1, cancer stem cell biomarker), KiSS-1 (suppressor of tumor metastasis), and metastasis associated in colon cancer-1 (MACC1) are all useful predictive factors for metastasis and prognosis in various cancers. In this study, we analyzed associations among VM, ALDH1, KiSS-1, and MACC1 in EOC, and their respective correlations with clinicopathological characteristics and survival in EOC. Methods: Positive rates of VM, ALDH1, KiSS-1, and MACC1 in 207 whole EOC tissue samples were detected by immunohistochemistry. Patients' clinical data were also collected. Results: Levels of VM, ALDH1, and MACC1 were significantly higher, and levels of KiSS-1 significantly lower, in EOC tissues than in benign ovary tumors. Levels of VM, ALDH1, KiSS-1, and MACC1 were associated significantly with tumor/lymph node/metastasis (LNM) grade, implantation, and International Federation of Gynecology and Obstetrics (FIGO) stage, and with patients' overall survival (OS); whereas the KiSS-1+ subgroup had significantly longer OS than did the KiSS-1- subgroup. In multivariate analysis, high VM, ALDH1 or MACC1 levels, FIGO stage, implantation and low KiSS-1 levels were independently associated with shorter OS in patients with EOC. Conclusions: VM and expressions of ALDH1, KiSS-1, and MACC1 represent promising markers for metastasis and prognosis, and potential therapeutic targets for EOC. [ABSTRACT FROM AUTHOR]

Background: Tumor recurrence and metastasis are the most common reason for treatment failure. Metastasis-associate in colon cancer-1 (MACC1) has been identified as a metastatic and prognostic biomarker for colorectal cancer and other solid tumors. Aldehyde dehydrogenase 1 (ALDH1), a marker of cancer stem cells, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or ALDH1 in non-small cell lung cancer (NSCLC) is unclear. In this study, we explored the relationship between MACC1 and ALDH1 expression, as well as their respective associations with clinicopathological features, to determine if either could be useful for improvement of survival prognosis in NSCLC. Methods: The expression levels of both MACC1 and ALDH1 in 240 whole tissue sections of NSCLC were examined by immunohistochemistry. Clinical data were also collected. Results: MACC1 and ALDH1 were significantly overexpressed in NSCLC tissues when compared to levels in normal lung tissues. Investigation of associations between MACC1 or ALDH1 protein levels with clinicopathological parameters of NSCLC revealed correlations between the expression of each with tumor grade, lymph node metastasis, and tumor node metastasis. The overall survival of patients with MACC1- or ALDH1-positive NSCLC tumors was significantly lower than that of those who were negative. Importantly, multivariate analysis suggested that positive expression of either MACC1 or ALDH1, as well as TNM stage, could be independent prognostic factors for overall survival in patients with NSCLC. Conclusions: MACC1 and ALDH1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for NSCLC. [ABSTRACT FROM AUTHOR]

Background: Cancer metastasis is a multi-step event including epithelial-to-mesenchymal transition (EMT). Breast cancer metastasis suppressor 1 (BRMS1) is a novel metastasis suppressor protein without anti-proliferating activity. However, a detailed underlying mechanism by which BRMS1 attenuates cancer cell EMT and invasion remained to be answered. In the present study, we report an additional mechanism by which BRMS1 attenuates Transforming growth factor-beta1 (TGF-β1)-induced breast cancer cell EMT and invasion.Methods: Experimental analysis involving chromosome immunoprecipitation (ChIP) and luciferase reporter assays were used to validate hypoxia inducible factor-1alpha (HIF-1α) as a transcriptional regulator of TWIST1 and Snail. Quantitative RT-PCR was used to analyze transcript expression. Immunoblotting and immunofluorescence were used to analyze protein expression. Matrigel-coated in vitro invasion insert was used to analyze cancer cell invasion.Results: BRMS1 strongly inhibited TGF-β1-induced breast cancer cell EMT and invasion. Unexpectedly, we observed that BRMS1 downregulates not only TWIST1 but also Snail expression, thereby inhibiting breast cancer cell invasion. In addition, we provide evidence that HIF-1α is required for Snail and TWIST1 expression. Further, BRMS1 reduced TGF-β1-induced HIF-1α transcript expression through inactivation of nuclear factor kappaB (NF-κB).Conclusion: Collectively, the present study demonstrates a mechanical cascade of BRMS1 suppressing cancer cell invasion through downregulating HIF-1α transcript and consequently reducing Snail and TWIST1 expression. [ABSTRACT FROM AUTHOR]

Background: KAI1 and epithelial-mesenchymal transition (EMT) is related to both angiogenesis and lymphangiogenesis and is an important target in new cancer treatment strategies. We aimed to investigate the KAI1 and marker of EMT expression and correlation with lymph node metastasis (LNM) and explore their prognostic impact in non-small cell lung cancer (NSCLC). Methods: Tumor tissue specimens from 312 resected patients with stage I-IIIA NSCLC were obtained. Immunohistochemistry was used to assess the expression of the molecular markers KAI1, E-cadherin (E-cad), vimentin, CD34, and D2-40. Results: There were 153 N0 and 159 N+ patients. Tumor cell expression of KAI1and the marker of EMT, lymphatic vessel density (LVD), and microvessel density (MVD) were related to LNM. In multivariate analyses, the ages of patients, high tumor cell KAI1 expression, EMT, and the scores of MVD were independent factor of prognosis. Conclusions: Tumor cell KAI1 expression, EMT, LVD, and MVD correlate with LNM. Thus, the detection of KAI1, expression of markers of EMT, and the scores of MVD may be used as a potential indicator of NSCLC prognosis. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80 % of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20 % suggesting poor prognosis. Methods: The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied. Results: MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 μM with an IC50 of 20 μM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 μM RACC was decreased by 49 and 76 % respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice. Conclusions: Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80 % of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20 % suggesting poor prognosis. Methods: The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied. Results: MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 μM with an IC50 of 20 μM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 μM RACC was decreased by 49 and 76 % respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice. Conclusions: Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Background Microtubule-associated protein tau (MAPT) is a neuronal protein involved in the pathogenesis of several neurodegenerative diseases including Parkinson's Disease (PD). Glycogen synthase kinase 3 beta (GSK3B) catalyzes phosphorylation in multiple sites of tau protein. However, whether or not there is any association between the GSK3B gene alteration, MAPT haplotype and PD remains unexplored in Chinese population, especially in central Chinese population. Results Here, we aimed at studying the effect of MAPT rs242562 and GSK3B rs334558 on the risk of PD by performing a case-control association study in central China. Our data showed that all PD patients and controls were of MAPT H1/H1 diplotype in our study, thus confirming that the distribution of the MAPT H1 haplotype is common in China. GG genotype of MAPT rs242562 serves protection effect on PD risk in central Chinese population, while genotype of GSK3B rs334558 showed no difference between PD patients and controls. Conclusions We conclude that the MAPT rs242562 is associated with PD in central China in the background of MAPT H1/H1 diplotype. The GG genotype of rs242562 displays protection against PD in subgroup with GSK3B rs334558 T carrier. [ABSTRACT FROM AUTHOR]

Background Presently, CD133 is one of the hottest markers to characterize cancer stem cells and KAI1/CD82 is reported as an important marker for the metastasis and prognosis of many cancers. The purpose of our study is to explore the relationship between cancer stem cells (CSCs) marked by CD133 and KAI1/CD82 expression and the clinicopathological characteristics of patients with laryngeal squamous cell carcinoma (LSCC). Methods Immunohistochemical analysis was used to detect the expression of CD133 and KAI1/CD82 in 83 archival surgical specimens of human LSCC and 83 cases of normal laryngeal tissues. Results In LSCC, positive rates of 49.4% and 41.0% were obtained for CD133 and KAI1/CD82, respectively. The expression of CD133 in LSCC tissues was significantly higher than that in normal tissues (P < 0.001), and the expression of CD133 was positively associated with pTNM stage (P = 0.005), pathological grade (P = 0.001), and lymph node metastasis (P < 0.001). The reduced expression of KAI1/CD82 was present in LSCC tissues. The positive rate of KAI1/CD82 expression was negatively correlated with pTNM stage (P = 0.014), pathological grade (P < 0.001), and lymph node metastasis (P = 0.007). A correlation analysis showed that there was a negative relationship between the expression of CD133 and KAI1/CD82 protein in LSCC tissues (P < 0.001). By Kaplan-Meier analysis, the expression of CD133 was negatively correlated with overall survival (OS) (log-rank = 40.949, P < 0.001) and disease-free survival (DFS) (log-rank = 39.307, P < 0.001) time of LSCC. The expression of KAI1/CD82 was positively correlated with OS (log-rank = 40.279, P < 0.001) and DFS (log-rank = 39.271, P < 0.001) time of LSCC. Cox regression analysis: the expression of CD133 and KAI1/CD82, and pTNM stages were independent prognostic factors of LSCC (P < 0.05). Conclusions Thus the detection of CD133 and KAI1/CD82 proteins may be used as a potential indicator of LSCC prognosis. [ABSTRACT FROM AUTHOR]

Background: Hantaviruses cause acute hemorrhagic fever with renal syndrome (HFRS). Currently, several types of inactivated HFRS vaccines are widely used, however the limited ability of these immunogen to elicit neutralizing antibodies restricts vaccine efficacy. Development of an effective vaccine to overcome this weakness is must. Methods: In the present study, a recombinant pseudotyped lentivirus bearing the hantaan virus (HTNV) envelope glycoproteins (GP), rLV-M, was constructed. C57BL/6 mice were immunized with the rLV-M and a series of immunological assays were conducted to determine the immunogenicity of the recombinant pseudotyped lentivirus. The humoral and cell-mediated immune responses induced by rLV-M were compared with those of the inactivated HFRS vaccine. Results: Indirect immunofluorescence assay (IFA) showed the rLV-M expressed target proteins in HEK-293cells. In mice, the rLV-M efficiently induced GP-specific humoral responses and protection against HTNV infection. Furthermore, the rLV-M induced higher neutralizing antibody titers than the inactivated HFRS vaccine control. Conclusions: The results indicated the potential of using a pseudotyped lentivirus as a delivery vector for a hantavirus vaccine immunogen. [ABSTRACT FROM AUTHOR]

Streptococcus suis is one of the most common zoonotic pathogens, in humans and can cause meningitis, endocarditis, arthritis and sepsis. Human cases of Streptococcus suis infection have been reported worldwide, and most of those cases occurred in Asia. Hearing loss is the most common sequela of Streptococcus suis meningitis. Streptococcus suis infection complicated with acute cerebral infarction has rarely been reported. Therefore, to provide a reference for this disease, we reported a case of acute multiple brain infarctions associated with Streptococcus suis infection. In our report, a 69yearold male patient had Streptococcus suis meningitis and sepsis, which were associated with multiple acute cerebral infarctions in the pons and bilateral frontotemporal parietal occipital lobes. After treatment, the patient exhibited cognitive impairment, dyspraxia and irritability. There are limited case reports of cerebral infarction associated with Streptococcus suis infection, and further research is needed to determine the best treatment method. [ABSTRACT FROM AUTHOR]

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12944-020-01416-2 [ABSTRACT FROM AUTHOR]

Objective: TCP1 is one of the eight subunits of the TCP1 ring complex (TRiC) or the multi-protein mammalian cytosolic chaperone complex. TRiC participates in protein folding and regulates the expression of multiple signaling proteins and cytoskeletal components in cells. Although the clinical importance of its subunits has been clarified in various carcinomas, the function of TCP1 in ovarian cancer (OC) remains unclear. We aimed to identify the association between the expression of TCP1 and the development of epithelial OC (EOC) and patient prognosis, and explore the underlying mechanisms of TCP1 on the tumor progression of OC cells. Methods: TCP1 protein expression was tested in various ovarian tissues by immunohistochemistry, and the correlation between TCP1 expression and clinical physiologic or pathologic parameters of patients with EOC was analyzed. The relationship between TCP1 expression and the prognosis of patients with OC was investigated and analyzed using the Kaplan–Meier (KM) plotter online database. The expression level of TCP1 was then tested in different OC cell lines by Western blotting. Further, a model using OC cell line A2780 was constructed to study the functions of TCP1 in growth, migration, and invasion of human EOC cells. Finally, the possible regulating signaling pathways were discussed. Results: TCP1 protein expression in OC or borderline tissues was significantly higher than that in benign ovarian tumors and normal ovarian tissue. The upregulated expression of TCP1 in OC was positively associated with the differentiation grade and FIGO stage of tumors and predicted poor clinical outcomes. Compared with IOSE-80 cells, TCP1 protein was overexpressed in A2780 cells. TCP1 knockdown using shRNA lentivirus inhibited the viability of A2780 cells. Western blotting showed that the phosphatidylinositol-3 kinase (PI3K) signaling pathway was activated in the tumor invasion in EOC driven by TCP1. Conclusion: Upregulated TCP1 is correlated with the poor prognosis of patients with OC. The mechanism of cancer progression promoted by TCP1 upregulation may be linked to the activation of the PI3K signaling pathway, and TCP1 may serve as a novel target for the treatment of OC. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80 % of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20 % suggesting poor prognosis. Methods: The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied. Results: MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 μM with an IC50 of 20 μM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 μM RACC was decreased by 49 and 76 % respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice. Conclusions: Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated an association between male sperm quality and assisted reproduction outcomes, focusing on the effects of individual parameters and reaching controversial conclusions. The WHO 6th edition manual highlights a new semen assay, the sperm DNA fragmentation index, for use after routine semen examination. However, the combined effect of the sperm DNA fragmentation index (DFI) and routine semen parameters remains largely unknown. Methods: We assessed the combined effect of the sperm DFI and conventional semen parameters on single fresh conventional IVF outcomes for infertile couples from January 1, 2017, to December 31, 2020. IVF outcomes were obtained from the cohort database follow-up records of the Clinical Reproductive Medicine Management System of the Third Affiliated Hospital of Guangzhou Medical University. An unsupervised K-means clustering method was applied to classify participants into several coexposure pattern groups. A multivariate logistic regression model was used for statistical analysis. Results: A total of 549 live births among 1258 couples occurred during the follow-up period. A linear exposure–response relationship was observed among the sperm DFI, sperm motility, and IVF outcomes. In multivariable adjustment, increased sperm DFI values and decreased sperm motility and semen concentration levels were associated with reduced odds of favourable IVF outcomes. Four coexposure patterns were generated based on the sperm DFI and the studied semen parameters, as follows: Cluster 1 (low sperm DFI values and high sperm motility and semen concentration levels), Cluster 2 (low sperm DFI values and moderate sperm motility and semen concentration levels), Cluster 3 (low sperm DFI values and low sperm motility and semen concentration levels) and Cluster 4 (high sperm DFI values and low sperm motility and semen concentration levels). Compared with those in Cluster 1, participants in Cluster 3 and Cluster 4 had lower odds of a live birth outcome, with odds ratios (95% confidence intervals [CIs]) of 0.733 (0.537, 0.998) and 0.620 (0.394, 0.967), respectively. Conclusions: When combined with low sperm DFI values, there was no significant difference between high or moderate sperm concentration and motility levels, and both were associated with favourable IVF outcomes. Low sperm parameter levels, even when DFI values remain low, may still lead to poor IVF outcomes. Participants with high sperm DFI values and low sperm motility and semen concentration levels had the worst outcomes. Our findings offer a novel perspective for exploring the joint effects of sperm DFI and routine semen parameter values. [ABSTRACT FROM AUTHOR]

Background: Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted.Methods: We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records.Results: The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05).Conclusion: Brucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis. [ABSTRACT FROM AUTHOR]

Background: Cancer incidence and mortality have been increasing in China, making cancer the leading cause of death since 2010 and a major public health concern in the country. Cancer stem cells have been studied in relation to the treatment of different malignancies, including gastric cancer. Anticancer bioactive peptide-3 (ACBP-3) can induce the apoptosis of gastric cancer stem cells (GCSCs) and reduce their tumorigenicity. In the present study, for the first time, we used a miRNA microarray and bioinformatics analysis to identify differentially expressed miRNAs in ACBP-3- treated GCSCs and GCSC-derived tumors in a xenograft model and functionally verified the identified miRNAs. miR- 338-5p was selected based on its significant upregulation by ACBP-3 both in cultured GCSCs and in tumor tissues. Results: miR-338-5p was downregulated in GCSCs compared with normal gastric epithelial cells, and the ectopic restoration of miR-338-5p expression in GCSCs inhibited cell proliferation and induced apoptosis, which correlated with the upregulation of the pro-apoptotic Bcl-2 proteins BAK and BIM. We also found that ACBP-3-treated GCSCs could respond to lower effective doses of cisplatin (DDP) or 5-fluorouracil (5-FU), possibly because ACBP-3 induced the expression of miR-338-5p and the BAK and BIM proteins and promoted GCSC apoptosis. Conclusions: Our data indicate that miR-338-5p is part of an important pathway for the inhibition of human gastric cancer stem cell proliferation by ACBP-3 combined with chemotherapeutics. ACBP-3 could suppress GCSC proliferation and lower the required effective dose of cisplatin or 5-fluorouracil. Therefore, this study provides not only further evidence for the remarkable anti-tumor effect of ACBP-3 but also a possible new approach for the development of GCSC-targeting therapies. [ABSTRACT FROM AUTHOR]

Background: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. Methods: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. Results: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. Conclusions: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines. [ABSTRACT FROM AUTHOR]

Background: The content and wording of the Patient Reported Outcome Measurement Information System (PROMIS) Physical Function and Pain Interference item banks have not been qualitatively assessed by individuals with knee joint impairments. The purpose of this investigation was to identify items in the PROMIS Physical Function and Pain Interference Item Banks that are irrelevant, unclear, or otherwise difficult to respond to for individuals with impairment of the knee and to suggest modifications based on cognitive interviews.Methods: Twenty-nine individuals with knee joint impairments qualitatively assessed items in the Pain Interference and Physical Function Item Banks in a mixed-methods cognitive interview. Field notes were analyzed to identify themes and frequency counts were calculated to identify items not relevant to individuals with knee joint impairments.Results: Issues with clarity were identified in 23 items in the Physical Function Item Bank, resulting in the creation of 43 new or modified items, typically changing words within the item to be clearer. Interpretation issues included whether or not the knee joint played a significant role in overall health and age/gender differences in items. One quarter of the original items (31 of 124) in the Physical Function Item Bank were identified as irrelevant to the knee joint. All 41 items in the Pain Interference Item Bank were identified as clear, although individuals without significant pain substituted other symptoms which interfered with their life.Conclusions: The Physical Function Item Bank would benefit from additional items that are relevant to individuals with knee joint impairments and, by extension, to other lower extremity impairments. Several issues in clarity were identified that are likely to be present in other patient cohorts as well. [ABSTRACT FROM AUTHOR]

Background: Microdissection testicular sperm extraction (micro-TESE) in combination with ICSI can make paternity possible for non-obstructive azoospermia (NOA) patients. Testicular sperm can be successfully retrieved in nearly half of NOA patients. Nevertheless, not many convincing protocols are established to improve sperm retrieval rate (SRR). The goal of this study was to evaluate whether gonadotropins therapy before micro-TESE could improve sperm retrieval rate and affect the ICSI outcomes in non-obstructive azoospermia patients with hypergonadotropic hypogonadism. Methods: This retrospective cohort study included a total of 569 non-obstructive azoospermia men who underwent micro-TESE with or without 3-month of preoperative hCG / hCG plus highly purified urinary FSH (uFSH) between January 2016 and December 2019. The primary outcome was the sperm retrieval rate of micro-TESE. Results: Sperm was found in 27 patients among 395 NOA men who accepted preoperative gonadotropins treatment (6.8%, 27/395) in post-treatment semen analysis for ICSI. One hundred forty nine out of 542 patients could successfully obtain enough sperm for ICSI through the micro-TESE (overall SRR = 27.5%). There was a statistically significant difference in the SRR between the preoperative gonadotropins treatment and non-gonadotropins treatment groups (31.2%, 115/368 vs. 19.5%, 34/174, P = 0.006). In the multivariable analysis with IPTW according to the propensity score, there was a significant association between preoperative gonadotropins treatment and the SRR (OR, 1.59; 95% CI: 1.02–2.52; P = 0.042). No differences in the clinical pregnancy rate, live birth delivery rate, or miscarriage rate were observed between the two groups. Conclusion: Preoperative gonadotropins therapy seems to have a role in improving SRR in NOA patients with hypergonadotropic hypogonadism. We found that gonadotropins therapy had no effect on ICSI clinical outcomes and live birth. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. Early diagnosis is critical for guiding the therapeutic management of ESCC. It is imperative to find more effective biomarkers of ESCC. Methods: To identify novel biomarkers for esophageal squamous cell carcinoma (ESCC), specimens from 10 patients with ESCC were subjected to a comparative proteomic analysis. The proteomic patterns of ESCC samples and normal esophageal epithelial tissues (NEETs) were compared using two-dimensional gel electrophoresis. And differentially expressed proteins were identified using MALDI-TOF-MS/MS. For further identification of protein in selected spot, western blotting and immunohistochemistry were employed. Results: Twelve proteins were up-regulated and fifteen proteins were down-regulated in the ESCC samples compared with the NEET samples. Up-regulation of galectin-7 was further confirmed by western blotting and immunohistochemistry. Furthermore, immunohistochemical staining of galectin-7 was performed on a tissue microarray containing ESCC samples (n = 50) and NEET samples (n = 10). The expression levels of galectin-7 were markedly higher in the ESCC samples than in the NEET samples (P = 0.012). In addition, tissue microarray analysis also showed that the expression level of galectin-7 was related to the differentiation of ESCC. Conclusions: The present proteomics analysis revealed that galectin-7 was highly expressed in ESCC tissues. The alteration in the expression of galectin-7 was confirmed using a tissue microarray. These findings suggest that galectin- 7 could be used as a potential biomarker for ESCC. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders characterized by recurrent abdominal pain associated with defecation or a change in bowel habits. Leading to significant negative effect on patients' quality of life and huge financial burden to health system, the management of IBS is a great challenge. Probiotics are considered as an effective therapy; however, in a lack of high-quality evidence of efficacy, no strain- and dose-specific probiotics were recommended in clinical guidelines. This study aims to evaluate the efficacy of the Bifidobacterium quadruple viable tablet in the treatment of IBS-D.Methods/design: A multicenter randomized controlled trial will be performed in fourteen hospitals. A total of three hundred patients who fulfill the eligibility criteria will be stratified divided into an experimental group and a control group randomly in a ratio of 1:1. The experimental group is treated with the Bifidobacterium quadruple viable tablet while the control group is treated with placebo. All the patients will receive a 4-week treatment and a 2-week follow-up. The primary outcome is the effectiveness in improving abdominal pain and stool consistency; the secondary outcome includes evaluation of overall symptom relief, frequency of defecation, bloating, urgency of defecation, remedial medication, score of IBS-QOL, and changes of microbiota and metabonomics. Physical examination, vital signs, laboratory tests, adverse events, and concomitant medication will be taken into account for intervention safety assessment during the trial.Discussion: This multicenter randomized controlled trial may provide high-quality evidence on the efficacy of the Bifidobacterium quadruple viable tablet for IBS-D on both physical and mental dimensions in China. To fill the gap of previous probiotic intervention studies, in addition, this study will also present safety assessment which will be a significant emphasis.Trial Registration: ChiCTR1800017721 . Registered on 10 August 2018. [ABSTRACT FROM AUTHOR]

Human brucellosis and fever of unknown origin. Zhi-guo Wu, Zhi-ying Song and Wei-xin Wang are co-first authors B Correction: BMC Infectious Diseases (2022) 22:868 b https://doi.org/10.1186/s12879-022-07872-8 Following publication of the original article [[1]], the authors identified an error in Table 1. [Extracted from the article]

Background: Although Taiwan has implemented several important interventions for various HIV-at-risk populations to combat the HIV epidemic, little is known regarding AIDS incidence at presentation and during follow-up among the various HIV-at-risk populations in Taiwan. A better understanding of AIDS incidence trends would help improve patient care and optimize public health strategies aimed at further decreasing HIV-related morbidity and mortality.Methods: Data from Taiwan Centers for Disease Control-operated Notifiable Diseases Surveillance System and Taiwan National Health Insurance Research Database (1998-2012) was divided into five cohort periods (consecutive 3-year groups). Logistic regression was employed to identify factors associated with AIDS incidence at presentation. Time-dependent Cox regression was used to identify factors associated with AIDS incidence during the follow-up period.Results: Of 22,665 patients [mean age: 32 years; male (93.03%)], 6210 (27.4%) had AIDS incidence over 2 (1.16) [median (interquartile range)] years of follow-up. AIDS developed in ≤3 months of HIV diagnosis in 73.6% AIDS patients. AIDS incidence trends at presentation and during follow-up differed according to HIV transmission routes over the five periods: AIDS at presentation increased in the sexual contact groups (P < 0.001 for homosexuals/heterosexuals; 0.648 for bisexuals) but decreased to a nadir in period 3 and then increased slightly in period 5 (P < 0.001) in people who injected drugs (PWIDs). AIDS incidence during the follow-up period increased from period 1 to a peak in period 3 or 4, before declining slightly in period 5, in the sexual contact groups (P < 0.001 for homosexuals/heterosexuals; 0.549 for bisexuals). However, it increased throughout the five periods in PWIDs (P < 0.001). Older age, sexual contact group versus PWIDs, high versus low income level, cohort periods, and HIV diagnosis regions helped predict AIDS at presentation and during follow-up.Conclusions: Disparities in AIDS incidence trends in various HIV-at-risk populations reflect different sociodemographic variables of HIV exposure and the adopted HIV prevention strategies. This study suggests the urgent need for tailored strategies aimed at specific populations at presentation and during follow-up. [ABSTRACT FROM AUTHOR]

Background: Brucellosis was a common human and livestock disease caused by Brucella strains, the category B priority pathogens by the US Center for Disease Control (CDC). Identified as a priority disease in human and livestock populations, the increasing incidence in recent years in China needs urgent control measures for this disease but the molecular background important for monitoring the epidemiology of Brucella strains at the national level is still lacking. Methods: A total of 600 Brucella isolates collected during 60 years (from 1953 to 2013) in China were genotyped by multiple locus variable-number tandem repeat analysis (MLVA) and the variation degree of MLVA11 loci was calculated by the Hunter Gaston Diversity Index (HGDI) values. The charts and map were processed by Excel 2013, and cluster analysis and epidemiological distribution was performed using BioNumerics (version 5.1). Results: The 600 representative Brucella isolates fell into 104 genotypes with 58 singleton genotypes by the MLVA11 assay, including B. melitensis biovars 2 and 3 (five main genotypes), B. abortus biovars 1 and 3 (two main genotypes), B. suis biovars 1 and 3 (three main genotypes), and B. canis (two main genotypes) respectively. While most B. suis biovar 1 and biovar 3 were respectively found in northern provinces and southern provinces, B. melitensis and B. abortus strains were dominant in China. Canine Brucellosis was only found in animals without any human cases reported. Eight Brucellosis epidemic peaks emerged during the 60 years between 1953 and 2013: 1955 - 1959, 1962 - 1969, 1971 - 1975, 1977 - 1983, 1985 - 1989, 1992 - 1997, 2000 - 2008 and 2010 - 2013 in China. Conclusions: Brucellosis has its unique molecular epidemiological patterns with specific spatial and temporal distribution according to MLVA. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) is the most commonly diagnosed type of lung cancer that is associated with poor prognosis. In this study we explored the potential role of p53-induced gene 3 (PIG3) in the progression of NSCLC. Methods: Immunohistochemistry was used to determine the expression levels of PIG3 in 201 NSCLC patients. We performed in vitro studies and silenced endogenous PIG3 by using specific siRNAs that specific target PIG3. Immunofluorescent staining was performed to determine the effect of PIG3 on mitotic progression in NSCLC cells. The growth rates of microtubules were determined by microtubule nucleation analysis. Cell proliferation and chemosensitivity were analyzed by CCK8 assays. Annexin V staining and β-galactosidase activity analysis were used to evaluate PIG3 deficiency-related apoptosis and senescence, respectively. Results: PIG3 expression levels negatively correlated with overall survival and disease-free survival of NSCLC patients. Knock down of PIG3 resulted in repressed proliferation of NSCLC cells and increased aberrant mitosis, which included misaligning and lagging chromosomes, and bi-or multi-nucleated giant cells. In addition, PIG3 contributed to mitotic spindle assembly by promoting microtubule growth. Furthermore, loss of PIG3 sensitized NSCLC cells to docetaxel by enhancing docetaxel-induced apoptosis and senescence. Conclusions: Our results indicate that PIG3 promotes NSCLC progression and therefore suggest that PIG3 may be a potential prognostic biomarker and novel therapeutic target for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Background: To better evaluate and improve the efficacy of dendritic cell (DC)-based cancer immunotherapy, we conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen (CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in the vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine efficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of vaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment. Methods: Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic colorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic colorectal cancer with 1 × 106 CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 106 CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the final DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical status. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation responses against CEA. Results: No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC vaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically significant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients. Conclusions: The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this protocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of patients. This treatment protocol should be further evaluated in additional colorectal cancer patients with modifications to enhance T cell responses. Trial registration: ClinicalTrials.gov (identifier NCT00154713), September 8, 2005. [ABSTRACT FROM AUTHOR]

Background: Many cancer cells exhibit reduced mitochondrial respiration as part of metabolic reprogramming to support tumor growth. Mitochondrial localization of several protein tyrosine kinases is linked to this characteristic metabolic shift in solid tumors, but remains largely unknown in blood cancer. Lymphocyte-specific protein tyrosine kinase (Lck) is a key T-cell kinase and widely implicated in blood malignancies. The purpose of our study is to determine whether and how Lck contributes to metabolic shift in T-cell leukemia through mitochondrial localization. Methods: We compared the human leukemic T-cell line Jurkat with its Lck-deficient derivative Jcam cell line. Differences in mitochondrial respiration were measured by the levels of mitochondrial membrane potential, oxygen consumption, and mitochondrial superoxide. Detailed mitochondrial structure was visualized by transmission electron microscopy. Lck localization was evaluated by subcellular fractionation and confocal microscopy. Proteomic analysis was performed to identify proteins co-precipitated with Lck in leukemic T-cells. Protein interaction was validated by biochemical co-precipitation and confocal microscopy, followed by in situ proximity ligation assay microscopy to confirm close-range (<16 nm) interaction. Results: Jurkat cells have abnormal mitochondrial structure and reduced levels of mitochondrial respiration, which is associated with the presence of mitochondrial Lck and lower levels of mitochondrion-encoded electron transport chain proteins. Proteomics identified CR6-interacting factor 1 (CRIF1) as the novel Lck-interacting protein. Lck association with CRIF1 in Jurkat mitochondria was confirmed biochemically and by microscopy, but did not lead to CRIF1 tyrosine phosphorylation. Consistent with the role of CRIF1 in functional mitoribosome, shRNA-mediated silencing of CRIF1 in Jcam resulted in mitochondrial dysfunction similar to that observed in Jurkat. Reduced interaction between CRIF1 and Tid1, another key component of intramitochondrial translational machinery, in Jurkat further supports the role of mitochondrial Lck as a negative regulator of CRIF1 through competitive binding. Conclusions: This is the first report demonstrating the role of mitochondrial Lck in metabolic reprogramming of leukemic cells. Mechanistically, it is distinct from other reported mitochondrial protein tyrosine kinases. In a kinaseindependent manner, mitochondrial Lck interferes with mitochondrial translational machinery through competitive binding to CRIF1. These findings may reveal novel approaches in cancer therapy by targeting cancer cell metabolism. [ABSTRACT FROM AUTHOR]

Background: Many cancer cells exhibit reduced mitochondrial respiration as part of metabolic reprogramming to support tumor growth. Mitochondrial localization of several protein tyrosine kinases is linked to this characteristic metabolic shift in solid tumors, but remains largely unknown in blood cancer. Lymphocyte-specific protein tyrosine kinase (Lck) is a key T-cell kinase and widely implicated in blood malignancies. The purpose of our study is to determine whether and how Lck contributes to metabolic shift in T-cell leukemia through mitochondrial localization. Methods: We compared the human leukemic T-cell line Jurkat with its Lck-deficient derivative Jcam cell line. Differences in mitochondrial respiration were measured by the levels of mitochondrial membrane potential, oxygen consumption, and mitochondrial superoxide. Detailed mitochondrial structure was visualized by transmission electron microscopy. Lck localization was evaluated by subcellular fractionation and confocal microscopy. Proteomic analysis was performed to identify proteins co-precipitated with Lck in leukemic T-cells. Protein interaction was validated by biochemical co-precipitation and confocal microscopy, followed by in situ proximity ligation assay microscopy to confirm close-range (<16 nm) interaction. Results: Jurkat cells have abnormal mitochondrial structure and reduced levels of mitochondrial respiration, which is associated with the presence of mitochondrial Lck and lower levels of mitochondrion-encoded electron transport chain proteins. Proteomics identified CR6-interacting factor 1 (CRIF1) as the novel Lck-interacting protein. Lck association with CRIF1 in Jurkat mitochondria was confirmed biochemically and by microscopy, but did not lead to CRIF1 tyrosine phosphorylation. Consistent with the role of CRIF1 in functional mitoribosome, shRNA-mediated silencing of CRIF1 in Jcam resulted in mitochondrial dysfunction similar to that observed in Jurkat. Reduced interaction between CRIF1 and Tid1, another key component of intramitochondrial translational machinery, in Jurkat further supports the role of mitochondrial Lck as a negative regulator of CRIF1 through competitive binding. Conclusions: This is the first report demonstrating the role of mitochondrial Lck in metabolic reprogramming of leukemic cells. Mechanistically, it is distinct from other reported mitochondrial protein tyrosine kinases. In a kinaseindependent manner, mitochondrial Lck interferes with mitochondrial translational machinery through competitive binding to CRIF1. These findings may reveal novel approaches in cancer therapy by targeting cancer cell metabolism. [ABSTRACT FROM AUTHOR]

Background: Mutations of the glucocerebrosidase (GBA) gene have reportedly been associated with Parkinson disease (PD) in various ethnic populations such as Singaporean, Japanese, Formosan, Canadian, American, Portuguese, Greek, Brazilian, British, Italian, Ashkenazi Jewish, southern and southwestern Chinese. The purpose of this study is to determine in central China whether or not the reported GBA mutations remain associated with PD. Methods: In this project, we conducted a controlled study in a cohort of 208 central Chinese PD patients and 298 controls for three known GBA mutations (L444P, N370S and R120W). Results: Our data reveals a significantly higher frequency of L444P mutation in GBA gene of PD cases (3.4%) compared with the controls (0.3%) (P = 0.007, OR = 10.34, 95% CI = 1.26 - 84.71). Specifically, the frequency of L444P mutation was higher in the late onset PD (LOPD) cases compared with that in control subjects. The N370S and R120W mutations were detected in neither the PD group nor the control subjects. Conclusions: Our observations demonstrated that the GBA L444P mutation confers genetic risk for PD, especially LOPD, among the population in the central China area. [ABSTRACT FROM AUTHOR]

Measuring health and health-related quality of life (HRQoL) is important for tracking the health of individuals and populations over time. Generic HRQoL measures allow for comparison across health conditions. One form of generic HRQoL measures are profile measures, which provide a description of health across several different domains (such as physical functioning, depression, and pain). Recent advances in health profile measurement include the development of measures based on item response theory. The Patient-Reported Outcomes Measurement Information System (PROMIS®) has been constructed using this theory. Another form of generic HRQoL measures are utility measures, which assess the value of health states. Multi-attribute utility theory provides a framework for valuing disparate domains of health and aggregating them into a single preference-based score. Such a score provides an overall measure of health outcomes as well as a quality of life weight for use in decision analyses and cost-effectiveness analyses. Developing a utility score for PROMIS® would allow simultaneous estimation of both health profile and utility scores using a single measure. The purpose of this paper is to provide a roadmap of the methodological steps necessary to create such a scoring system. [ABSTRACT FROM AUTHOR]

Background: The Chinese term "Hot Qi" is often used by parents to describe symptoms in their children. The current study was carried out to estimate the prevalence of using the Chinese term "Hot Qi" to describe symptoms in children by their parents and the symptomatology of "Hot Qi". Method: A cross sectional survey by face-to-face interview with a semi-structured questionnaire was carried out in a public hospital and a private clinic in Hong Kong. The parental use of the term "Hot Qi", the symptoms of "Hot Qi" and the remedies used for "Hot Qi" were asked. Results: 1060 pairs of children and parents were interviewed. 903 (85.1%) of parents claimed that they had employed the term "Hot Qi" to describe their children's symptoms. Age of children and place of birth of parents were the predictors of parents using the term "Hot Qi". Eye discharge (37.2%), sore throat (33.9%), halitosis(32.8%), constipation(31.0%), and irritable (21.2%) were the top five symptoms of "Hot Qi" in children. The top five remedies for "Hot Qi" were the increased consumption of water (86.8%), fruit (72.5%), soup (70.5%), and the use of herbal beverages "fiveflower- tea" (a combination of several flowers such as Chrysanthemum morifolii, Lonicera japonica, Bombax malabaricum, Sophora japonica, and Plumeria rubra) (57.6%) or selfheal fruit spike (Prunella vulgaris) (42.4%). Conclusion: "Hot Qi" is often used by Chinese parents to describe symptoms in their children in Hong Kong. Place of birth of parents and age of the children are main factors for parents to apply the term "Hot Qi" to describe symptoms of their children. The common symptoms of "Hot Qi" suggest infections or allergy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to devise a Cancer symptoms Discrimination Scale (CSDS) suitable for China based on a cross-sectional survey. Methods: The CSDS was developed using the classical measurement theory. A total of 3610 students from Yunnan province, China, participated in the cross-sectional survey. The test version of the scale was modified by the item analysis method, and after the official version of CSDS was developed, its reliability and validity were verified. A univariate analysis of variance and a multiple linear regression model were used to analyze the influencing factors of cancer symptoms discrimination among the university/college students. Results: There were 21 items in total for the CSDS, including 3 subscales --- common clinical manifestations (11 items), physical appearance defects (6 items), and drainage tube(s) wearing (4 items). This CSDS had good validity (GFI = 0.930, AGFI = 0.905, RMR = 0.013, I-CVIs> 0.80, and the Pearson correlation coefficient was satisfactory.) and reliability (Cronbach's alpha = 0.862, spearman-brown coefficient = 0.875). The multiple linear regression showed that certain factors may affect the students' discrimination level against cancer symptoms (P < 0.05), including gender, major, current education degree, guardian's highest record of formal schooling, self-rated health status, history of care for cancer patients, family relationship, ways of cancer knowledge acquisition, good/poor understanding of cancer-related information, degree of cancer fear, and their perception of cancer infectiousness. Conclusion: This CSDS, with good reliability and validity, can be used for the evaluation of the discrimination risk and levels against cancer symptoms among healthy students. [ABSTRACT FROM AUTHOR]