Search

Five new iridoid glucosides, cannabifolisides A–E (1 – 5), together with nine analogues (6 – 14), were isolated from the leaves of Vitex negundo var. cannabifolia. Their structures were elucidated by spectroscopic data (NMR, UV, IR, and MS) analyses and comparison of their spectroscopic and physical data with the literature values. The protective effect of isolated compounds on human gastric epithelial cells were evaluated by measuring the enhanced cell viability of GES-1 cell insulted by TCA. Among these, compounds 4, 6, 8, 10, 12, and 14 remarkably increased the cell viability in a concentration-depend manner.

We report an unconventional effect of synchrotron X-ray irradiation in which Co–O bonds in thermally annealed (Y, Co)-codoped CeO2 nanocrystal samples were formed due to, instead of broken by, X-ray irradiation. Our experimental data indicate that escaping oxygen atoms from X-ray-broken Ce–O bonds may be captured by Co dopant atoms to form additional Co–O bonds. Consequently, the Co dopant atoms were pumped by X-rays from the energetically-favored thermally-stable Co-O4 square-planar structure to the metastable octahedral Co-O6 environment, practically a reversal of thermal annealing effects in (Y, Co)-codoped CeO2 nanocrystals. The band gap of doped CeO2 with Co dopant in the Co-O6 structure was previously found to be 1.61 eV higher than that with Co in the Co-O4 environment. Therefore, X-ray irradiation can work with thermal annealing in opposing directions to fine tune and optimize the band gap of the material for specific technological applications.

Background CTCs play a critical role in the diagnosis and prognosis of liver cancer. However, there are few studies on whether different types of CTCs can predict the prognosis in patients with HCC following LT. Methods Retrospective data including CTCs detected by the CanPatrolTM platform combined with RNA-ISH were collected and analyzed on 56 patients from December 2016 to December 2019 at the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. Results During the study period, fifty-six patients (51 males, 5 females) were included with an mean age of 52 ± 9 years. The 1-, 2- and 3-year recurrence rates of postoperative interstitial CTC-positive and CTC-negative groups were 21.7% vs 10.8%, 37.5% vs 10.8% and 55.5% vs 10.8%, confirming a statistically significant difference between the 2 groups (p = 0.044). The 1-, 2- and 3-year recurrence rates of the increasing interstitial CTCs group were 25.2%, 36.9% and 66.9%, while 12.6%, 24.4% and 24.4% in the decreasing and unchanged group, indicating a significant difference (p = 0.038). Conclusion CanPatrolTM platform presents a superior analytical sensitivity, and may be used as a dynamic monitoring tool for CTCs. And interstitial CTCs which are more aggressive and metastatic caused by EMT can be regarded as a predictor of post-transplant tumor recurrence after LT for HCC.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a pathogenesis that has not been fully elucidated. With the development of the theory of the gut-liver axis and the deepening of related research, the role of the intestinal tract in the pathogenesis of NAFLD has been investigated more. Intestinal microbiota, intestinal metabolites, and intestinal epithelial and immune-based barriers constitute the intestinal environment, which uses crosstalk to maintain the homeostasis of the intestinal environment. This paper reviews the progress in the study of intestinal microbiota, intestinal environment, and NAFLD and suggests that repair of intestinal functional balance may be a new idea for early prevention and intervention of NAFLD.

Purpose To evaluate the changes of cytokines and immune cells after Intra-articular hyaluronic acid(IAHA)injections in patients with knee osteoarthritis (KOA). Patients and Methods Sixteen patients were included in the study, with a total of 65 IAHA injections. The Numeric Rating Scale (NRS) and Lysholm scores were evaluated at each visit. The immune cells and 14 cytokines of synovial fluid were analyzed at each visit. The association between immune cells and cytokines were examined. Results IL-6 and IL-8 were the most common cytokines in the synovial fluid of KOA patients. The synovial fluid was orchestrated by macrophages (69%) and Lymphocytes (18%). Neutrophils were less to count of the total cell population ( Conclusion The synovial fluid of KOA patients was orchestrated by macrophages (69%) and Lymphocytes (18%) and cytokines like IL-6 and IL-8. IAHA may play an anti-inflammatory functional role through the decreased production of IL-6 and IL-8 by macrophages through polarization. The results from this study partially revealed the effect of IAHA on cytokines and immune cells change in KOA patients, and therapies targeting pathogenic cytokines and immune cells might be used to attenuate the knee joint inflammation and release pain. Trial registration ChiCTR2100050133; date registered 17 August 2021.

Background aims Mesenchymal stromal cells (MSCs) provide minor salivary glands (MSGs) with support and niche cells for epithelial glandular tissue. Little is known about resident MSG-derived MSCs (MSG-MSCs) in primary Sjӧgren's syndrome (PSS). The authors’ objective is to define the immunobiology of endogenous PSS MSG-MSCs. Methods Using culture-adapted MSG-MSCs isolated from consenting PSS subjects (n = 13), the authors performed in vitro interrogation of PSS MSG-MSC immunobiology and global gene expression compared with controls. To this end, the authors performed phenotypic and immune functional analysis of indoleamine 2,3-dioxygenase (IDO), programmed death ligand 1 (PD-L1) and intercellular adhesion marker 1 (ICAM-1) before and after interferon γ (IFNγ) licensing as well as the effect of MSG-MSCs on T-cell proliferation. Considering the female predominance of PSS, the authors also addressed the influence of 17-β-estradiol on estrogen receptor α-positive-related MSC function. Results The authors found that MSG-MSCs deployed normal immune regulatory functionality after IFNγ stimulation, as demonstrated by increased protein-level expression of IDO, PD-L1 and ICAM-1. The authors also found that MSG-MSCs suppressed T-cell proliferation in a dose-dependent manner independent of 17-β-estradiol exposure. Gene ontology and pathway analysis highlighted extracellular matrix deposition as a possible difference between PSS and control MSG-MSCs. MSG-MSCs demonstrated increased α-smooth muscle actin expression in PSS, indicating a partial myofibroblast-like adaptation. Conclusions These findings establish similar immune regulatory function of MSG-MSCs in both PSS and control patients, precluding intrinsic MSC immune regulatory defects in PSS. PSS MSG-MSCs show a partial imprinted myofibroblast-like phenotype that may arise in the setting of chronic inflammation, providing a plausible etiology for PSS-related glandular fibrosis.

We report the experimental observation of and theoretical explanation for the reduction of dopant ions and enhancement of magnetic properties in Ce-doped TiO2 diluted magnetic semiconductors from UV-light irradiation. Substantial increase in Ce3+ concentration and creation of oxygen vacancy defects in the sample due to UV-light irradiation was observed by X-ray and optical methods. Magnetic measurements demonstrate a combination of paramagnetism and ferromagnetism up to room temperatures in all samples. The magnetization of both paramagnetic and ferromagnetic components was observed to be dramatically enhanced in the irradiated sample. First-principle theoretical calculations show that valence holes created by UV irradiation can substantially lower the formation energy of oxygen vacancies. While the electron spin densities for defect states near oxygen vacancies in pure TiO2 are in antiferromagnetic orientation, they are in ferromagnetic orientations in Ce-doped TiO2. Therefore, the ferromagnetically-oriented spin densities near oxygen vacancies created by UV irradiation are the most probable cause for the experimentally observed enhancement of magnetism in the irradiated Ce-doped TiO2.

Systemic inflammation, linked with abnormal mitochondrial viscosity, is reported to be associated with cerebro-cardiovascular disease and Alzheimer's disease. Therefore, it is of great significance to detect the mitochondrial viscosity to indicate the inflammatory signal in vivo. Considering the strategies of fluorescent molecular rotors (FMRs) and fluorescence lifetime imaging microscopy (FLIM), we have rationally designed a novel mitochondrial viscosity-specific fluorescent probe Mito-VCI, based on coumarin fluorophores with benzo[e]indolium as the rotor group. In a high viscosity solution system, the fluorescence lifetime of the probe Mito-VCI was prolonged due to the planarization and rigidity enhancement of the molecular rotor. Satisfactorily, the probe was only sensitive to viscosity, instead of non-viscosity factors such as pH and polarity. Furthermore, the probe sensitively targeted mitochondria in HeLa cells with a Pearson's correlation of 0.93, and specifically detected dynamics variation of mitochondrial viscosity with FLIM imaging in HeLa cells induced by LPS. Notably, significant fluorescence lifetime changes of Mito-VCI between normal and inflammatory tissues also occurred (for example, the fluorescence lifetime in the spleen changed from 1.128 to 1.432 ns). It can be inferred from the above observations that Mito-VCI could work as an effective and sensitive fluorescent molecular rotor for mitochondrial viscosity monitoring through FLIM imaging with a systemic inflammatory response, and provide potential applications for the diagnosis of systemic inflammation in pharmacology and toxicology studies.

Background Primary duodenal tuberculosis is very rare. Due to a lack of specificity for its presenting symptoms, it is easily misdiagnosed clinically. Review of the few case reports and literature on the topic will help to improve the overall understanding of this disease and aid in differential diagnosis to improve patient outcome. Case summary A 71-year-old man with a 30-plus year history of bronchiectasis and bronchitis presented to the Gastroenterology Department of our hospital complaining of intermittent upper abdominal pain. Initial imaging examination revealed a duodenal space-occupying lesion; subsequent upper abdominal contrast-enhanced computed tomography indicated duodenal malignant tumor. Physical and laboratory examinations showed no obvious abnormalities. In order to confirm further the diagnosis, electronic endoscopy was performed and tissue biopsies were taken. Duodenal histopathology showed granuloma and necrosis. In-depth tuberculosis-related examination did not rule out tuberculosis, so we initiated treatment with anti-tuberculosis drugs. At 6 mo after the anti-tuberculosis drug course, there were no signs of new development of primary lesions by upper abdominal computed tomography, and no complications had manifested. Conclusion This case emphasizes the importance of differential diagnosis for gastrointestinal diseases. Duodenal tuberculosis requires a systematic examination and physician awareness.

Purpose Genome-wide association studies (GWAS) have identified multiple genetic variants associated with leprosy. To investigate the single and combined associations between single-nucleotide polymorphisms (SNPs) and the development of leprosy, we therefore performed generalized multi-analytical (GMDR) analysis in Chinese leprosy household contacts and constructed a risk prediction model. Patients and Methods This case-control study included 229 leprosy cases and 233 healthy household contacts in Zhejiang province, China. Participants were genotyped for 17 polymorphisms selected from GWAS. The Pearson χ2 test, logistic regression and GMDR analysis were performed to investigate gene-gene interactions and construct a risk prediction model for leprosy. Results The genotype and the allele distributions of rs142179458, rs2275606, rs663743 and rs73058713 were significantly different between patients and controls. rs2275606, rs6478108, rs663743 and rs73058713 showed an association after adjusting for sex and age in the logistic regression. A five-way interaction model consisting of rs2058660, rs2275606, rs4720118, rs6478108 and rs780668 was chosen as the optimal model for determining leprosy susceptibility. The model classified 237 (51.3%) into the low-risk group and 225 (48.7%) individuals into the high-risk group. The area under the curve (AUC) of this model was 0.757 (95% CI: 0.712-0.803), and the odds ratio for leprosy between the high- and low-risk groups was 9.733 (95% CI: 6.384-14.960; P

Background Pasteurella multocida is an important and old zoonotic pathogen worldwide which has an impressive host spectrum including numerous domestic and wild animals as well as birds, causing specific diseases or outbreak with great economic impact. It has never been reported that P. multocida can cause an epidemic in wild rodents. In June 5–17, 2016, more than 1000 rodent deaths of an unknown cause quickly spread in the PuEr City, Yunnan province, southwestern China. Methods The rodents in affected areas and outside of the epidemic areas were collected and screened for possible known pathogens including Yersinia pestis, rabies virus and hantavirus as well as other bacteria. The possible bacterial pathogens were isolated both by culture medium and by mouse inoculation in parallel. The isolates were identified by the Vitek GNI card and PCR assays for 16S rRNA genes. The pathogen strains were selected for whole genome sequencing analysis. Results A total of 123 rodents were collected from 25 sample sites at affected area, among of which, all 119 dead rodents were negative for the pathogen under consideration except P. multocida, and all four live rodents were negative for P. multocida. In addition, 480 rodents collected from other 23 counties outside of the epidemic area in Yunnan were negative for with P. multocida. A total of 14 strains of P. multocida (six directly isolated from the field rodents and eight from the experimental mice that were injected with the organ substrates from the dead rodents) belonged to serogroup A and serogroup F represented by 9 N and 20 N were identified in these epidemic areas. Whole genome sequencing revealed that the serogroup F strain shared 99% similarity to P. multocida Pm70 from chicken, but contained a 50 k bp insertion sequence. The serogroup A strain shared 95% similarity to P. multocida FDAARGOS_385 from a human patient, but contained four large structural differences. Histological abnormalities were identified in the livers, lungs, hearts and brains of the inoculated mice. Conclusions The simultaneous occurrence of both serotypes of P. multocida may have caused this sudden onset of mortality across the local rodent population in Yunnan Province, China. Further attention should be paid to this old bacterium in the world.

Purpose The Gamma Knife (GK) Icon allows for the delivery of stereotactic radiosurgery using a thermoplastic mask in combination with intrafraction motion monitoring using high definition motion management. The system pauses treatment if the magnitude of motion in all directions exceeds 1 to 1.5 mm, causing a break in treatment and prolongation of the session. We reviewed the records of patients treated in a frameless manner on our GK Icon system to determine predictors for treatment interruption. Methods and Materials We reviewed the records of patients treated between May 2019 and May 2020 on the GK Icon using a frameless technique for brain metastases, gliomas, schwannomas, and meningiomas. We recorded treatment time as noted in the plan document, actual treatment delivery time, and any pauses in treatment. We tabulated baseline characteristics including age, gender, diagnosis, performance status, and shifts at time of treatment. We used a receiver operating curve analysis to determine a timepoint corresponding with treatment interruption. We then conducted a logistic regression analysis to generate odds ratios for likelihood of treatment. Results We identified 150 patients meeting inclusion criteria. The majority (82%) were patients with brain metastases. The median age was 63 and the median dose was 27 Gy (16-30 Gy) in 3 fractions (1-5 fractions). The median treatment time was 23 minutes (4-108 minutes). Sixty-nine patients (46%) had at least 1 pause in treatment (range, 1-7). Receiver operating curve analysis revealed treatment time >19 minutes and rotation >0.47 degrees to be associated with interruption. Multivariable logistic regression revealed rotation >0.47 degrees and treatment time >19 minutes as predictive of interruption. Conclusions For patients with rotations exceeding 0.47 degrees or an extended treatment time, physicians should expect treatment interruptions, consider fractionation to lessen table time, or use a frame-based approach.

Objective: Based on epidemiological field data, this study was to develop a prediction model which can be used as a preliminary screening tool to identify pregnant women who were at high risk of offspring congenital heart disease (CHD) in Nanchong City, and be beneficial in guiding prenatal management and prevention. Methods: A total of 367 children with CHD and 367 children without congenital malformations aged 0 to 14 years old were recruited from the Affiliated Hospital of North Sichuan Medical College and Nanchong Central Hospital between March 2016 and November 2018. Using the SPSS 22.0 case-control matching module, the controls were matched to the cases at a rate of 1:1, according to the same gestational age of child (premature delivery or full-term), the maternal age of pregnancy (less than 1 year). 327 matched case-control pairs were analyzed by SPSS 22. Univariate and multivariate analysis were performed to find the important maternal influencing factors of offspring CHD. A logistic regression disease prediction model was constructed as the final predictors, and Hosmer-Lemeshow goodness of fit test and receiver operating characteristic (ROC) curve were used to evaluate the model. Results: 654 subjects (327 cases and 327 controls) were matched. The 25 variables were analysed. The logistic regression model established in this study was as follows: Logit(P)= -2.871+(0.686×respiratory infections)+(1.176×water pollution)+(1.019×adverse emotions during pregnancy) - (0.617×nutrition supplementation). The Hosmer-Lemeshow chi-square value was 7.208 (df = 6), with a nonsignificant p value of 0.302, which indicates that the model was well-fitted. The calibration plot showed good agreement between the bias-corrected prediction and the ideal reference line. Area under the ROC curve was 0.72 (95% CI: 0.681~0.759), which means that the predictive power of the model set fitted the data. Conclusion: In Nanchong city, more attention should be paid to mother who had a history of respiratory infections, exposure to polluted water, adverse emotions during pregnancy and nutritional deficiency. The risk model might be an effective tool for predicting of the risk of CHD in offspring by maternal experience during pregnancy, which can be used for clinical practise in Nanchong area.

Purpose Diffuse large B cell lymphoma (DLBCL) is an aggressive B-cell malignancy with clinical and molecular heterogeneity whose genetics may have clinical implications for patient stratification and treatment. The circulating tumor DNA (ctDNA) is a novel noninvasive, real-time, and tumor-specific biomarker harboring tumor-derived genetic alterations that are identical to those of tumor cells, thus showing great promise in individualized medicine, including precise diagnosis, prediction of prognosis, response monitoring, and relapse detection for DLBCL. Patients and methods In this study, we applied NGS analysis to tumor biopsies and ctDNA samples from 16 DLBCL subjects. Then, we compared the genomic alterations from 41 newly diagnosed patients and 56 relapsed/refractory (R/R) patients. Results Our results show that ctDNA can function as a liquid biopsy for tracking recurrently mutated genes in DLBCL (sensitivity: 87.50%). The mutational profiles of newly diagnosed and R/R DLBCL groups largely overlapped, but the frequencies of some gene mutations differ between the two cohorts. The distribution of mutations also revealed different frequencies in the two cohorts due to different signaling pathways. Genes from apoptosis pathway, immune response and BCR pathway suffered more mutations in R/R patients. Conclusion Overall, this study establishes ctDNA as an easily accessible source of tumor DNA for DLBCL genotyping and provides a deeper understanding of the somatic alteration spectrum for both newly diagnosed and R/R DLBCL patients.

Campylobacter coli and Campylobacter Jejuni are highly resistant to most therapeutic antimicrobials in Taiwan; rapid diagnostics of resistance in bacterial isolates is crucial for the treatment of campylobacteriosis. We characterized 219 (40 C. coli and 179 C. jejuni) isolates recovered from humans from 2016 to 2019 using whole-genome sequencing to investigate the genetic diversity among isolates and the genetic resistance determinants associated with antimicrobial resistance. Susceptibility testing with 8 antimicrobials was conducted to assess the concordance between phenotypic resistance and genetic determinants. The conventional and core genome multilocus sequence typing analysis revealed diverse clonality among the isolates. Mutations in gyrA (T86I, D90N), rpsL (K43R, K88R), and 23S rRNA (A2075G) were found in 91.8%, 3.2%, and 6.4% of the isolates, respectively. The horizontally transferable resistance genes ant(6)-I, aad9, aph(3′)-IIIa, aph(2″), bla(OXA), catA/fexA, cfr(C), erm(B), lnu, sat4, and tet were identified in 24.2%, 21.5%, 33.3%, 11.9%, 96.3%, 10.0%, 0.9%, 6.8%, 3.2%, 13.2%, and 96.3%, respectively. High-level resistance to 8 antimicrobials in isolates was 100% predictable by the known resistance determinants, whereas low-level resistance to azithromycin, clindamycin, nalidixic acid, ciprofloxacin, and florfenicol in isolates was associated with sequence variations in CmeA and CmeB of the CmeABC efflux pump. Resistance-enhancing CmeB variants were identified in 62.1% (136/219) of isolates. In conclusion, an extremely high proportion of C. coli (100%) and C. jejuni (88.3%) were multidrug-resistant, and a high proportion (62.5%) of C. coli isolates were resistant to azithromycin, erythromycin, and clindamycin, which would complicate the treatment of invasive campylobacteriosis in this country.

Sexual dimorphism is exhibited remarkably in the female predominance of autoimmune diseases (e.g. systemic lupus erythematosus, female-to-male ratio 9 : 1). To understand the female bias in autoimmunity, we focused on vestigial-like family member 3 (VGLL3), a molecule with increased expression in females and known to promote autoimmunity. We report that VGLL3 mediates the cellular stress response by upregulating p53 and IL-17C. Energy stress allows VGLL3 to be induced by IFNα, which ultimately leads to p53-dependent, lupus-associated, inflammatory cell death. Our results suggest that female-biased expression of VGLL3 helps cells adapt to metabolic stress, which, intriguingly, is known as a significant challenge during the evolution of placental mammals due to the need to feed a developing embryo. The findings also uncover the importance of maintaining metabolic homeostasis in the prevention of autoimmunity.

Objective Association of postoperative peripheral CD4+ T cells percentage and recurrence in colorectal cancer (CRC) remains to be explored. Therefore, we aimed to investigate the association between the postoperative peripheral CD4+ T cells percentage and recurrence in CRC patients. Patients and methods Consecutive stage I-III CRC patients without neoadjuvant treatment undergoing curative resection from January 2010 to July 2016 were identified in two Chinese centers. The association between the postoperative CD4+ T cells percentage, measured within 12 weeks after surgery, and recurrence-free survival (RFS) was analyzed. Results A total of 1028 patients were identified (training set: 913 patients, validation set: 115 patients). In the training set, the 5-year RFS rate of the 441 patients with abnormal postoperative CD4+ T cells percentage was significantly lower than that of those with normal percentage (70.3% [95% CI 65.7-75.2%] vs 77.6% [95% CI 73.7-81.7%] and unadjusted hazard ratio [HR] 1.36 [95% CI 1.04-1.78], P=0.02). The result was confirmed in the validation set. Multivariable Cox regression analysis demonstrated that the association of postoperative CD4+ T cells percentage with 5-year RFS was independent both in the training and validation sets. In propensity score matching analysis, patients with normal postoperative CD4+ T cells percentage were found to have a favourable response to adjuvant chemotherapy (HR 0.29 [95% CI 0.12-0.72], P=0.008). Conclusion Postoperative peripheral CD4+ T cells percentage is a predictive biomarker for RFS in patients with CRC, which can identify those who will benefit from adjuvant chemotherapy.

Background Lymphedema is a chronic, debilitating and incurable disease that affects 0.13%-2% of the global population. Emerging evidence indicates that adipose-derived stem cells (ADSCs) might serve as suitable seed cells for lymphatic tissue engineering and lymphedema therapy. Aim To summarize applications of ADSCs for treating lymphedema in both animal studies and clinical trials. Methods A systematic search was performed on four databases - PubMed, Clinicaltrials.gov, the evidence-based Cochrane Library, and OVID - using the following search string: ("lymphedema" or "lymphoedema" or "lymphangiogenesis") and ("adipose-derived stem cells" or "adipose-derived stromal cells" or "adipose-derived regenerative cells"). A manual search was performed by skimming the references of relevant studies. Animal studies and clinical trials using adipose-derived cells for the treatment of any kind of lymphedema were included. Results A total of eight research articles published before November 2019 were included for this analysis. Five articles focused on animal studies and another three focused on clinical trials. ADSC transplantation therapy was demonstrated to be effective against lymphedema in all studies. The animal studies found that coadministration of ADSCs and controlled-release vascular endothelial growth factor-C or platelet-rich plasma could improve the effectiveness of ADSC therapy. Three sequential clinical trials were conducted on breast cancer-related lymphedema patients, and all showed favorable results. Conclusion ADSC-based therapy is a promising option for treating lymphedema. Large-scale, multicenter randomized controlled trials are needed to develop more effective and durable therapeutic strategies.

Purpose To investigate the effect of Danggui Buxue Tang (DBT) on intestinal microbiota diversity after fermentation by Bacillus subtilis. Methods B. subtilis was used to ferment DBT. Sprague Dawley (SD) rats were randomly divided into the following four groups with six rats in each group: the control group, DBT nonfermentation group, B. subtilis group, and DBT fermentation group. Rats were fed continuously for 14 days. The 16S rRNA of faecal samples was analysed by high-throughput Illumina sequencing. Results In total, 3483 operational taxonomical units (OTUs) were identified in this study, and 1236 OTUs were shared among all samples. Moreover, the most abundant phyla identified in this study were Bacteroidetes (29.65–38.19%) and Firmicutes (48.30–67.04%). The F/B ratios of the DBT nonfermentation group (1.07%) and the DBT fermentation group (1.78%) were slightly lower than those of the control group (2.29%). Lactobacillus was most upregulated in the DBT fermentation group (38.4%), followed by the DBT nonfermentation group (18.97%), control group (14.61%), and probiotics group (8.39%). Moreover, the pathogenic bacteria Alistipes and Parabacteroides were found to be downregulated in the DBT fermentation group (the percentages of Alistipes and Parabacteroides were as follows: control group, 8.09% and 0.16%; DBT nonfermentation group, 4.31% and 0.37%; DBT fermentation group, 1.96 and 0.09%; and probiotics group, 6.25% and 0.12%, respectively). Conclusion This study is the first to research systematically the effects of DBT on the diversity of rat intestinal microbiota before and after fermentation. The structural characteristics of complex bacterial community in each group were clearly analysed, and DBT significantly increases probiotics and inhibits pathogenic bacterial growth in the intestinal tract of rats after fermentation, which plays a significant role in maintaining the balance of the intestinal microbiota of the rats. This research provides new insights into the development and utilization of traditional Chinese medicine.

Nonhereditary factors play an important role in the occurrence of congenital heart disease (CHD). This study was to explore the possible parental nonhereditary exposure factors relevant to the occurrence of CHD in the northeastern Sichuan area. A total of 367 children with CHD and 367 children without congenital malformations aged 0 to 14 years old were recruited from the Affiliated Hospital of North Sichuan Medical College and Nanchong Central Hospital between March 2016 and November 2018. This study was designed as a case-control study with 1:1 frequency matching, in which the parents of cases and controls were interviewed with the same questionnaire according to the gestational age of the child, maternal age during pregnancy and the same maternal race/ethnicity. Then, 322 matched case-control pairs were analysed by SPSS 22. Thirty-one suspicious factors were entered into the binary logistic regression analysis after univariate regression analysis of 55 factors (alpha = 0.05). The analysis results showed that 7 factors were significantly associated with the occurrence of CHD. Thus, augmenting maternal mental healthcare, improving the quality of drinking water, obtaining adequate nutrition, maintaining a healthy physical condition during pregnancy, enhancing parents’ level of knowledge and maintaining a healthy lifestyle may lower the occurrence of CHD.

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma and a limited number of cases have been reported from China. This study aimed to investigate the clinicopathological features of newly diagnosed PCNSLs from a single center in eastern China and to identify the potential prognostic factors for overall survival (OS) and progression-free survival (PFS). All consecutive patients with histopathologically diagnosed PCNSLs at our center between January 2003 and October 2017 were recruited. Demographic and clinicopathological data were collected and reviewed retrospectively. The potential risk factors for OS and PFS were identified using the log-rank test and Cox regression analysis. A total of 167 immunocompetent cases were enrolled. The median age was 58 years (range 17-96 years), and the male:female ratio was 3:2. Headache (n = 65; 39%) and cerebral hemisphere (n = 96; 57%) were the most common presenting complaint and location, respectively. Out of 167 cases, 150 cases were diffuse large B cell lymphomas. With a median follow-up of 25 months (range 1-152 ), the median OS and PFS were 37 months (95% CI, 25-49) and 17 months (95% CI, 13-20), respectively. Residual tumor after operation, chemotherapy without HD-MTX and palliative treatment was revealed as independent prognostic markers. Moreover, ECOG > 3, multifocal lesions, and palliative treatment were revealed as unfavorable independent prognostic markers for PFS. In conclusion, Chinese patients with PCNSL have distinct characteristics. Further studies are warranted to confirm the prognostic value of these factors and to optimize treatments for these patients.

BACKGROUND Worldwide, hepatocellular carcinoma (HCC) accounts for 80-90% of all cases of primary liver cancer, and is one of the ten most common malignancies. This study used bioinformatics analysis to identify genes associated with patient outcome in stages I-IV HCC and the gene pathways that distinguished between normal liver and liver cells and HCC and human HCC cell lines. MATERIAL AND METHODS Target genes were defined as those that had marketed drugs or drugs under development targeting a specific gene and acquired from the Clarivate Analytics Integrity Database. Differential expression gene analysis, co-expression network analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, survival analysis and receiver operating characteristic (ROC) curve analysis were used to explore the similarities and differences in gene expression profiles, functional associations, and survival in stage I-IV HCC. Normal liver cells (HL-7702) and HCC cell lines (HepaRG, HepG2, SK-Hep1, and Huh7) were studied using Western blot and quantitative reverse transcription PCR (RT-qPCR). RESULTS Hierarchical gene clustering identified target genes that distinguished between HCC and normal liver tissue. For stages I-IV HCC, there were seven commonly upregulated target genes EPHB1, LTK, NTRK2, PTK7, TBK1, TIE1, and TLR3, which were mainly involved in immune and signaling transduction pathways. PTK7 was highly expressed in stage I-IV HCC and was an independent prognostic marker for reduced overall survival (OS). CONCLUSIONS Bioinformatics analysis, combined with patient survival analysis, identified PTK7 gene expression as a potential therapeutic target and prognostic biomarker for all stages of HCC.

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from Surveillance Epidemiology and End Results database with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general US population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during study period. While age and surgery positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, more recent year (2001-2015) of diagnosis as well as multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM, which may be helpful for risk stratification and therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

Background: Though denosumab is an effective treatment for osteoporosis, the rebound effect after discontinuation has drawn investigators' attention. It includes a dramatic loss of gained bone mineral density (BMD) and an increased risk of vertebral fractures. This prospective multi-institutional randomized controlled trial aims to investigate whether zoledronate prevents loss of BMD after discontinuation of denosumab. The trial was registered as Denosumab Sequential Therapy (DST) trial in March 2019 at clinicaltrials.gov, with the identifier NCT03868033.Methods: The study is conducted at National Taiwan University Hospital and its branches. Patients who have continuously received denosumab treatment for two or more years are surveyed for eligibility. Baseline characteristics and questionnaires of life quality are recorded after recruitment. BMD, circulating levels of bone turnover markers (BTMs), including serum N-terminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide (CTX), are checked before the stratified randomization to 4 groups. Biological sex and the T-scores are used to create 4 strata. The participants in group 1 adhere to regular denosumab therapy for another 2 years. All the other patients receive on-time zoledronate treatment in the first year. The participants in group 2, 3, and 4 have on-time denosumab, on-time zoledronate and drug holiday in the second year, respectively. BMDs are checked annually. Pre-scheduled checkpoints of BTMs are also arranged. For patient safety, rescue treatment with another injection of zoledronate will be applied to the patients on drug holiday if the CTX levels raise above the pre-specified threshold, 0.573 ng/mL for women and 0.584 ng/mL for men. The primary outcomes are the percentage changes of BMDs in lumbar spine, total hip and femoral neck. The secondary outcomes include the changes of serum level of the BTMs, new osteoporotic fractures, extra zoledronate injections needed in group 4 and the differences of quality of life.Discussion: We aim to provide evidence whether zoledronate prevents bone loss after denosumab cessation. To our knowledge, the study has the largest sample size. No other randomized controlled study included all the three different treatment strategies and a positive control. It is also the first associated randomized controlled trial outside Europe.

Currently, multiple circular RNAs (circRNAs) have been verified to act as essential regulators in the progression of gastric cancer (GC). We aimed to investigate the role of circ_0008035 in GC progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to measure the expression of circ_0008035 and miR-599. 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was employed to evaluate cell proliferation and ferroptosis. Western blot assay was performed to measure the levels of cyclin D1, proliferating cell nuclear antigen (PCNA) and eukaryotic initiation factor 4A1 (EIF4A1). Flow cytometry analysis was conducted to assess cell apoptosis. The iron accumulation, lipid peroxidation and mitochondrial membrane potential were examined by relevant kits. Dual-luciferase reporter assay was conducted to determine the targeting relationship between miR-599 and circ_0008035 or EIF4A1. A murine xenograft model was established to investigate the function of circ_0008035 in vivo. Circ_0008035 was up-regulated in GC tissues and cells. Silencing of circ_0008035 repressed cell proliferation and induced cell apoptosis and ferroptosis in GC cells. Circ_0008035 acted as a sponge of miR-599. The effects of circ_0008035 knockdown on GC cell proliferation, apoptosis and ferroptosis were abolished by miR-599 inhibition. EIF4A1 was confirmed to be a target gene of miR-599. Circ_0008035 knockdown inhibited EIF4A1 expression by targeting miR-599. Moreover, the suppressive role of circ_0008035 deficiency in GC progression could be restored by EIF4A1. Additionally, circ-0008035 knockdown hampered tumorigenesis in vivo. Circ_0008035 promoted GC cell growth and repressed apoptosis and ferroptosis by up-regulating EIF4A1 through sponging miR-599.

Heng Zhao,1,* Li-Dan Zhang,2,* Li-Fang Liu,1 Chun-Qing Li,3 Wei-Li Song,3 Yong-Yang Pang,1 Yun-Liang Zhang,1 Dan Li4 1Endocrinology Laboratory, The First Central Hospital of Baoding, Baoding, Hebei Province, 071000, People’s Republic of China; 2Department of Nuclear Medicine, The First Central Hospital of Baoding, Baoding, Hebei Province, 071000, People’s Republic of China; 3Outpatient Department, The First Central Hospital of Baoding, Baoding, Hebei Province, 071000, People’s Republic of China; 4Department of Ophthalmology, Affiliated Hospital of Hebei University, Baoding, Hebei Province, 071000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dan LiDepartment of Ophthalmology, Affiliated Hospital of Hebei University, Baoding, Hebei Province, 071000, People’s Republic of ChinaTel +86 189 31251885Fax +86 031 25981539Email drli_ld@163.comYun-Liang ZhangEndocrinology Laboratory, The First Central Hospital of Baoding, Baoding, Hebei Province, 071000, People’s Republic of ChinaTel +86 137 31251133Fax +86 0312-5976520Email zyl_zhang98@163.comPurpose: This study aimed to describe the levels of glycated hemoglobin (HbA1c), D-dimer (D-D), and fibrinogen (FIB) in different types of diabetic retinopathy (DR).Methods: A total of 61 patients with diabetes, who were treated in our department between November 2017 and May 2019, were selected. According to their non-mydriatic fundus photography and fundus angiography results, patients were divided into three groups, ie, the non-DR (NDR) group (n=23), the non-proliferative DR (NPDR) group (n=17), and the proliferative DR (PDR) group (n=21). A control group of 20 people who had tested negative for diabetes was also included. The levels of HbA1c, D-D, and FIB were measured and compared, respectively.Results: The mean values of HbA1c were 6.8% (5.2%, 7.7%), 7.4% (5.8%, 9.0%), and 8.5% (6.3%, 9.7%) in the NDR, NPDR, and PDR groups, respectively. The control group values were 4.9% (4.1%, 5.8%). These results indicated a significant statistical difference between groups. The mean values of D-D were 0.39 ± 0.21 mg/L, 1.06 ± 0.54 mg/L, and 1.39 ± 0.59 mg/L in the NDR, NPDR, and PDR groups, respectively. The control group result was 0.36 ± 0.17 mg/L. The values of the NPDR and PDR groups were significantly higher than those of the NDR and control groups, and the value of the PDR group was significantly higher than that of the NPDR group, indicating a significant difference between the groups (P < 0.001). The mean values of FIB were 3.07 ± 0.42 g/L, 4.38 ± 0.54 g/L, and 4.46 ± 1.09 g/L in the NDR, NPDR, and PDR groups, respectively. The control group result was 2.97 ± 0.67 g/L. The difference between the groups was statistically significant (P < 0.05).Conclusion: Blood levels of HbA1c, D-D, and FIB in the PDR group were significantly higher than in the NPDR group.Keywords: glycated hemoglobin, HbA1c, D-dimer, D-D, fibrinogen, FIB, diabetic retinopathy, DR, microangiopathy

Mother-to-child transmission (MTCT) is the major cause of chronic infection of hepatitis B virus (HBV) in patients. However, whether and how HBV crosses the placenta to cause infection in utero remains unclear. In this study, we investigate the mechanism as to how the HBV virions pass through layers of the trophoblast. Our data demonstrate the exocytosis of virions from the trophoblast after exposure to HBV where the endocytosed HBV virions co-localized with an S100A10/AnxA2 complex and LC3, an autophagosome membrane marker. Knockdown of either AnxA2 or S100A10 in trophoblast cells led to a reduction of the amount of exo-virus in Transwell assay. Immunohistochemistry also showed a high expression of AnxA2 and S100A10 in the placental tissue samples of HBV-infected mothers with congenital HBV-positive infants (HBV+/+). We conclude that in HBV intrauterine infection and mother-to-child transmission, a proportion of HBV hijacks autophagic protein secretion pathway and translocate across the trophoblast via S100A10/AnxA2 complex and multivesicular body (MVB)-mediated exocytosis. Our study provides a potential target for the interference of the mechanisms of HBV intrauterine infection and mother-to-child transmission., Mother-to-child transmission is the major cause of chronic hepatitis B virus (HBV) infection. This study shows that an unconventional protein secretion pathway that depends on autophagy may be hijacked by HBV to complete the process of intracellular transport. In HBV-infected trophoblasts, AnxA2-S100A10-mediated exocytosis may result in HBV intrauterine transmission.

The investigation of filtration and loading performance of fibrous filters with different structures is of high importance for designing filters with long lifetime used in applications with high soot concentrations. Penetration of the soot agglomerates and NaCl particles (with the mobility diameters of 50, 80, 100, 200 and 300 nm) through two types of composite filter media (with the nanostructured layer of electrospun nanofibers and PTFE membrane, respectively) was analyzed. Meanwhile, evolution of the experimental and modeled pressure drop during the particles loading process at the velocities of 6.7 and 11.1 cm/s was also studied. The cake thickness was measured by a new and non-contact method utilizing a 3D optical profiler which would not alter the cake structure. The results showed that the soot penetration was lower than that of NaCl particles under the same condition, because the soot agglomerates had larger effective interception length than the NaCl particles with the same mobility diameter. The pressure drop of the filters loaded with soot agglomerates increased faster than that with NaCl particles. Furthermore, the pressure drop increased faster at the velocity of 11.1 cm/s because of formation of more compact cake. In addition, the pressure drop of the filter with a lower solidity nanostructured layer increased slower because more particles could penetrate into its inner part. The model data agreed with the experimental data well in the case of soot loading. Our results indicate that the filters which have relatively low filtration efficiency against the standard compact aerosol particles yet sufficient efficiency against the soot agglomerates and an open structure can be used in the applications with high soot concentrations to gain a long lifetime.

Middle- and long-term outcomes of multi-segmental lumbar spinal stenosis treated with Dynesys stabilization (DS) have rarely been reported. Older age and multi-segmental degeneration may be positive factors in achieving satisfactory outcomes following DS. The present study aimed to compare the middle- and long-term outcomes of DS with lumbar fusion for treatment of multi-segmental lumbar spinal stenosis (ms-LSS) in elderly patients. This study retrospectively analyzed patients with ms-LSS treated by DS or lumbar fusion from January 2011 to April 2013. Twenty-two patients were included in the Dynesys group, and 44 patients treated by lumbar fusion and rigid fixation were included in the fusion group. Clinical outcomes were assessed by VAS and ODI. Radiological outcomes were measured by range of motion (ROM) of stabilized segments and the proximal adjacent segment, intervertebral disc height (DH) and L1–S1 lumbar lordosis angle (LL). Modified Pfirrmann grade score was used to access disc degeneration. The mean follow-up time of the Dynesys group and fusion group was 68.50 ± 6.40 and 70.14 ± 7.26 months, respectively. Baseline data were similar between the two groups. There were no significant differences between the two groups in terms of improvement of clinical outcomes (VAS and ODI). DS preserved a certain degree of ROM (3.74 ± 2.00) of surgical segments. ROM of proximal adjacent segment underwent an increase in both groups at the final follow-up. The DH of the surgical segments and proximal adjacent segment in both groups was significantly lower than that before surgery (P = 0.000). LL of both groups improved (P = 0.000), and there was no significant difference between the two groups. The modified Pfirrmann score of proximal adjacent segment of both groups increased at the final follow-up. The fusion group underwent a more significant increase (P = 0.000), whereas the inter-group difference showed no significance (P = 0.090). DS is a safe and effective surgical treatment of multi-segmental lumbar spinal stenosis in the elderly population. DS preserves a certain degree of mobility of surgical segments.

When the cartilage on the prominent ears is reshaped, the arising stress returns the tissue to its initial configuration. Laser irradiation of areas of maximal stress leads to stress relaxation and results in a stable configuration. Sixty auricles were harvested from 30 New Zealand white rabbits and cut into a rectangle measuring 50 mm by 25 mm with an average thickness of approximately 1.3 mm. Bilateral skin was included for ex vivo studies. Continuous cryogen spray cooling (CSC) with laser energy was delivered to the exposed cartilage for reshaping. In clinical applications, from January 2006 to December 2016, a total of 50 patients with 100 bat ears who underwent CO2 laser reshaping (otoplasty) were assessed. A continuous cooling system (4 °C) in conjunction with a CO2 laser was applied to make a retroauricular-approached incision and reshape the ear cartilage. The well cartilage bending correlated with the different parameters demonstrated in the continuous CSC protected group. All 100 (100%) of the subjects experienced early complications (≤ 1 month) related to laser exposure with swelling, while 5 (5%) experienced ecchymosis, 2 (2%) minimal hematoma, 2 (2%) scarring, 1 (1%) minor infection, 1 (1%) under correction, 1 (1%) overcorrection, and 1 (1%) relapse. These problems were corrected and/or had resolved after 3 months. All patients achieved good to excellent results in our final outcome assessment (> 6 months). Laser reshaping has a potential use in certain surgical procedures involving the cartilage. The appropriate conditions for laser ear reshaping clearly depend on the laser wavelength used, energy controlling, and tissue optical properties.

The mesenchymal stem cell (MSC) is a potential strategy in the pretreatment of traumatic acute lung injury (ALI), a disease that causes inflammation and oxidative stress. This study aimed to investigate whether MSC-exosomal microRNA-124-3p (miR-124-3p) affects traumatic ALI. Initially, a traumatic ALI rat model was established using the weight-drop method. Then, exosomes were obtained from MSCs of Sprague-Dawley rats, which were injected into the traumatic ALI rats. We found that miR-124-3p was abundantly-expressed in MSCs-derived exosomes and could directly target purinergic receptor P2X ligand-gated ion channel 7 (P2X7), which was overexpressed in traumatic ALI rats. After that, a loss- and gain-of-function study was performed in MSCs and traumatic ALI rats to investigate the role of miR-124-3p and P2X7 in traumatic ALI. MSC-derived exosomal miR-124-3p or silenced P2X7 was observed to increase the survival rate of traumatic ALI rats and enhance the glutathione/superoxide dismutase activity in their lung tissues. However, the wet/dry weight of lung tissues, activity of methylenedioxyamphetamine and H2O2, and levels of inflammatory factors (TNF-a, IL-6, and IL-8) were reduced. Similarly, the numbers of total cells, macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage fluid were also reduced when treated with exosomal miR-124-3p or silenced P2X7. In conclusion, the results provide evidence that miR-124-3p transferred by MSC-derived exosomes inhibited P2X7 expression, thus improving oxidative stress injury and suppressing inflammatory response in traumatic ALI, highlighting a potential pretreatment for traumatic ALI.

As a heterogeneous group of clonal disorders, acute myeloid leukemia with internal tandem duplication of fms-like tyrosine kinase 3 (FLT3-ITD) mutation usually shows an inferior prognosis. In the present study, we found that homoharringtonine (HHT), a protein translation inhibitor of plant alkaloid in China, exhibited potent cytotoxic effect against FLT3-ITD (+) cell lines and primary leukemia cells, and a remarkable synergistic anti-leukemia action was demonstrated in vitro and in vivo in xenograft mouse models when co-treated with the heat shock protein 90 inhibitor IPI504. Mechanistically, HHT combined with IPI504 synergistically inhibited the growth of leukemia cells by inducing apoptosis and G1 phase arrest. This synergistic action resulted in a prominent reduction of total and phosphorylated FLT3 (p-FLT3) as well as inhibition of its downstream signaling molecules such as STAT5, AKT, ERK and 4E-BP1. Furthermore, co-treatment of HHT and IPI504 led to a synergistic or additive effect on 55.56%(10/18) of acute myeloid leukemia cases tested, including three relapsed/refractory patients. In conclusion, our findings indicate that the combination of HHT and HSP90 inhibitor provides an alternative way for the treatment of FLT3-ITD positive acute myeloid leukemia, especially for relapsed/refractory AML.

Ultraviolet (UV) light irradiation on CeO2 nanocrystals catalysts has been observed to largely increase the material’s catalytic activity and reactive surface area. As revealed by x-ray absorption near edge structure (XANES) analysis, the concentration of subvalent Ce3+ ions in the irradiated ceria samples progressively increases with the UV-light exposure time. The increase of Ce3+ concentration as a result of UV irradiation was also confirmed by the UV-vis diffuse reflectance and photoluminescence spectra that indicate substantially increased concentration of oxygen vacancy defects in irradiated samples. First-principle formation-energy calculation for oxygen vacancy defects revealed a valence-hole-dominated mechanism for the irradiation-induced reduction of CeO2 consistent with the experimental results. Based on a Mars-van Krevelen mechanism for ceria catalyzed oxidation processes, as the Ce3+ concentration is increased by UV-light irradiation, an increased number of reactive oxygen atoms will be captured from gas-phase O2 by the surface Ce3+ ions, and therefore leads to the observed catalytic activity enhancement. The unique annealing-free defect engineering method using UV-light irradiation provides an ultraconvenient approach for activity improvement in nanocrystal ceria for a wide variety of catalytic applications.

Tubiechong (Eupolyphaga sinensis) is an important material used in traditional Chinese medicine (TCM). However, the immunoregulation effects of E. sinensis Lyophilized Powder (ESL) are uncl...

Objective A retrospective study was designed to evaluate the effectiveness of CT-guided core needle biopsy in diagnosing spinal lesions through comparison with C-arm guidance. Methods From April 2013 to July 2017, a total of 188 patients, who suffered from spinal lesions or had malignant tumor history with a new spinal fracture, were included in this study. There were 96 men and 92 women, with an average of 57.1 years. A total of 238 core needle biopsies were performed. A total of 140 core needle biopsies were carried out under C-arm guidance in 102 patients (group 1); 98 core needle biopsies were carried out under CT guidance in 86 patients (group 2); 108 core needle biopsies were performed in thoracic vertebrae, 116 were in lumbar vertebrae, and 14 were in sacral vertebrae. Seventy-eight patients accepted surgical treatment after biopsies. For these patients, the histological pathologies of the biopsy and surgery were compared to evaluate the accuracy of the biopsy. For the other 110 patients who did not receive surgical treatment, the treatment response and the clinical course were used to evaluate the accuracy of the biopsy. The success rate, the diagnostic accuracy rate, the true positive/negative rate, and complications of the two groups were calculated and compared. Results There were no significant differences in sex, age, and lesion sites between the C-arm guidance group (group 1) and the CT guidance group (group 2). There were no complications in the two groups. Pathological diagnoses were established in 232 of 238 biopsies. They revealed that 52 were primary malignant tumors, 12 were benign tumors, 70 were metastatic tumors, 4 were tuberculosis, and 94 were classified as "other." The success rate of group 2 was higher than that of group 1, but it was not statistically significant (95.7% vs 100%; P = 0.098). According to the final diagnosis, the diagnostic accuracy rates were calculated and compared. There was no significant difference between the two groups (95.5% vs 96.9%; P = 0.835). The kappa coefficient was used to analyze the concordance between the histological pathologies of the biopsy and the final diagnosis in the two groups. The kappa values of the two group were 0.909 and 0.939, respectively. The results showed good consistency in both groups, but seemed better for group 2. Conclusion CT-guided core needle biopsy is a relatively safe and effective procedure for diagnosing spinal lesions with a high diagnostic accuracy rate and few complications.

Nanoscale lead (Pb) dioxide particles (nPbO2) are a newly identified corrosion product formed inside lead-bearing pipes or lead-containing faucets in drinking water distribution systems. These particles can release toxic lead ions, which cause drinking-water contamination and lead poisoning in humans, especially children. nPbO2 may be dislodged from pipes into drinking water; however, little research has focused on the bioavailability and toxicity of nPbO2in vivo. In this study, we used adult medaka fish (Oryzias latipes) as an animal model to investigate the uptake, lead dissolution, bioaccumulation and toxic effects of nanoscale [nPbO2] and microscale bulk [bPbO2] Pb dioxide and Pb(II)aq (Pb2+) in vivo upon acute to sub-chronic aqueous exposure. Both types of PbO2 particles were chemically stable in dechlorinated tap water with low water solubility. However, the X-ray absorption near-edge structure (XANES) analysis and analytical quantification of lead speciation showed that both nPbO2 and bPbO2 could be reductively dissolved into Pb(II)aq in both the intestine (major uptake route) and gills of the fish; thereby, enhancing hepatic Pb accumulation. The fish brains exhibited greater Pb accumulation and acetylcholinesterase inhibition with Pb(II)aq treatment than all the PbO2 treatments. The Pb content was greater in the gills, liver and brain with nPbO2 than bPbO2. This in vivo evidence implies the possibility of increased risk of exposure to Pb dissolution from PbO2 particles in the digestive system via drinking water, which can enhance the bioavailability of Pb uptake and toxicity in humans.

Objective The aims of this study were to clarify the histological features of adenoid basal carcinoma (ABC) and determine whether cytokeratin 17 (CK17) and Ki-67 can facilitate the differential diagnosis of ABC from squamous cell carcinoma (SCC). Materials and methods Nine cases of pure ABC were collected from the files of the Division of Pathology at the Zhejiang University Hospital Women's School of Medicine. For comparison, 20 cases of moderately to poorly differentiated cervical SCC, including 2 of basaloid SCC, were also retrieved from the same period. Blocks were recut, reread, and immunostained for CK17 and Ki-67. Results Morphologically, ABCs were mainly composed of small basaloid cell nests and variable squamous differentiation foci. For immunohistochemical staining, 1 of 9 cases showed diffuse CK17 staining, 5 of 9 showed focal positive staining, and 3 of 9 showed negative staining in the basaloid cell area of ABC, whereas no CK17 expression was found in ABC squamous foci. Eighteen of the 20 invasive SCCs showed diffuse CK17 staining, and 2 showed focal staining. The Ki-67 proliferative index varied in different ABC areas, with a relatively high index in squamous differentiation foci and a low index in basaloid cell areas. In contrast, Ki-67 staining was unevenly intense in SCC. Conclusions Adenoid basal carcinoma had characteristic morphological features, and the differential diagnosis of ABC from SCC is usually simple, based on morphology. In select cases, when histological findings are equivocal, the loss of CK17 expression in the squamous differentiation area, and a lower Ki-67 index in basal cell foci support ABC diagnosis.

Background: Myeloid-derived suppressor cells (MDSCs) may lead to immune evasion and disease progression in some cancers, but their roles remain to be investigated in cervical cancer. This study aimed to characterize the specific subsets of MDSCs that might be potential indicators for disease progression in cervical cancer patients. Methods: Different subsets of MDSCs were characterized using flow cytometry in blood samples from healthy subjects and cervical cancer patients. T-cell proliferation assay was performed in vitro. Tumor infiltrating CD8+ and FOXP3+ cells were also evaluated by immunostaining on the tumor tissues from patients with early and locally advanced cervical cancer. We further analyzed the relevance of circulating MDSCs to clinicopathological characteristics, patient survival as well as tumor infiltrating lymphocytes. Results: The frequency of circulating GrMDSCs increased correlated with FIGO stage while the percentage of MoMDSCs only elevated in patients with advanced cervical cancers. For patients with early and locally advanced cervical cancer, the frequency of circulating GrMDSCs but not MoMDSCs correlated with clinicopathologic parameters including metastatic lymph nodes, deep stromal invasion and tumor recurrence. The levels of circulating GrMDSCs also negatively correlated with the densities of CD8+ cells in tumor tissues. In vitro assay showed that Gr-MDSCs suppressed the proliferation of autologous T cells. Conclusion: Our study demonstrates that the increased frequency of circulating GrMDSCs is associated with tumor burden and recurrence in early and locally advanced cervical cancer patients, that the GrMDSCs may be potential biomarkers for disease progression cervical cancers.

Background Neoadjuvant chemotherapy (NACT) has been recently accepted as an effective alternative in patients with locally advanced cervical cancer. However, little is known about the effects of NACT on the immunological microenvironment in cervical cancers. In this study, we analyzed the alterations of tumor infiltrating lymphocytes (TILs) before and after NACT and analyzed their prognostic significance in advanced cervical cancer patients treated with platinum-based NACT. Methods We recruited 137 patients with stage Ib2 and IIa2 cervical cancer retrospectively. Pretreatment biopsy and surgical specimens after NACT were immunostained with CD8 and Foxp3. The densities of intratumoral and peritumoral immunopositive TILs were analyzed separately. Results Foxp3+ T cells density significantly decreased in both intratumoral (median 28.49 vs. 19.97; Z = − 8.635, p

Objective To evaluate safety and efficacy of pedicle screw with polymethyl methacrylate (PMMA) augmentation in unilateral transforaminal lumbar interbody fusion (uTLIF) in osteoporotic patients. Methods We randomly divided 50 osteoporotic patients with degenerative lumbar diseases diagnosed between February 2014 and November 2015 into 2 groups. One group underwent standard uTLIF, and the other group underwent uTLIF with PMMA augmentation. All patients were scheduled to attend a series of regular follow-up evaluations. Oswestry Disability Index, Japanese Orthopaedic Association score, visual analog scale score, lumbar lordotic angle, segmental lordotic angle, and disc space height (DSH) at each follow-up were collected and analyzed. Results The 2-year follow-up was completed by 24 patients in the uTLIF group and 23 patients in the PMMA group. Oswestry Disability Index, Japanese Orthopaedic Association score, and visual analog scale score showed significant improvements after surgery in both groups, with no significant difference between groups. DSH in the uTLIF group was 8.7 ± 2.3 mm and in the PMMA group was 10.7 ± 1.6 mm. Fusion rate in the uTLIF group was 19/24 and in the PMMA group was 21/23. DSH and fusion rate in the PMMA group were higher than those in the uTLIF group. No severe complications were observed after PMMA injection. Conclusions Pedicle screw with PMMA augmentation can increase fixation stability and reduce DSH loss in uTLIF. Moreover, PMMA in the vertebral body did not impede the interbody fusion ability in uTLIF.

Pancreatic cancer remains a challenging disease with an overall cumulative 5-year survival rate around 6%. Though significant progress has been made in the availability of diagnostic techniques and treatment strategies, pancreatic cancer remains a disease of high mortality rate. Therefore, there is an urgent need for a better understanding of the molecular mechanisms that governs the oncogenesis and metastasis process of pancreatic cancer. In the present study, by using the Cancer Genome Atlas (TCGA) dataset analysis, we demonstrated that sorting nexin 6 (SNX6) serves as a biomarker for predicting prognosis of pancreatic cancer. In vitro studies demonstrated that silencing of SNX6 expression reduced cell proliferation, colony formation, invasion, and metastasis. Higher level of SNX6 helps maintain the mesenchymal properties, which renders migration and invasive capacities to pancreatic cancer cells. Moreover, in the process of TGF-β-induced epithelial to mesenchymal transition (EMT), the expression level of SNX6 was increased, and silencing of SNX6 expression could inhibit the TGF-β-induced EMT program. These results collectively uncovered a novel predictive marker for pancreatic cancer and provided the possible underlying molecular mechanism.