[Clinical features and antimicrobial resistance of invasive non-typhoid Salmonella infection in children at Xiamen].

Objective: To investigate the clinical characteristics, serogroups and antimicrobial resistance of invasive non-typhoid Salmonella infection in children at Xiamen. Methods: Retrospective cohort study. The clinical manifestations, treatment, prognosis, serogroups and antimicrobial resistance of 29 hospitalized children with invasive non-typhoid Salmonella infection confirmed by blood, cerebrospinal fluid, bone marrow and other sterile body fluids or deep pus culture at the Department of Infectious Diseases, the Department of Orthopedics and the Department of General Surgery in Xiamen Children's Hospital from January 2016 to December 2021 were analyzed. According to the clinical diagnosis criteria, the patients were divided into sepsis group and non-sepsis group (bacteremia and local suppurative infection). The inflammatory markers, serogroups distribution and drug resistance were compared between the two groups. Comparison between groups using Mann-Whitney U test and χ2 test. Results: Among the 29 cases, there were 17 males and 12 females, with an onset age of 14 (9, 25) months, and 10 cases (34%) of patients were younger than 1 year old, 15 cases (52%) under 1 to 3 years old, and 4 cases (14%) greater than or equal 3 years old. The onset time of 25 cases (86%) was from April to September. The diseases included 19 cases (66%) septicemia (2 of which were combined with suppurative meningitis), 10 cases (34%) non-sepsis group, including 7 cases bacteremia and 3 cases local suppurative infection (2 cases of osteomyelitis, 1 case of appendicitis with peritonitis). The clinical manifestations were fever in 29 cases (100%), diarrhea and abdominal pain in 18 cases (62%), cough and runny nose in 10 cases (34%). Eighteen cases (62%) were cured and 11 cases (38%) were improved by effective antibiotics treatment. C-reactive protein in sepsis group was significantly higher than that in non-sepsis group (25.2 (16.1, 56.4) vs. 3.4 (0.5, 7.5) mg/L, Z=-3.81, P<0.001).The serogroups of C, B and E were the most prevalent among non-typhoid Salmonella isolates, accounting for 10 cases (34%), 9 cases (31%) and 7 cases (24%) respectively. Antibacterial drug sensitivity test showed that the sensitivity rates of imipenem, ertapenem and piperaciratazobactam were all 100% (31/31), those of ceftazidime, ceftriaxone, and cefepime were 94% (29/31), 94% (29/31) and 97% (30/31) respectively. The drug resistance rates of ampicillin, ampicillin-sulbactam and trimethoprim-sulfamethoxazole were 51% (16/31), 48% (15/31) and 48% (15/31) respectively, those of cefazolin, cefotetan, tobramycin, gentamicin and amikacinwere all 100% (31/31). There were no significant differences in the drug resistance rates of ceftazidime, ceftriaxone, aztreonam, ampicillin-sulbactam, ampicillin, trimethoprim-sulfamethoxazole and ciprofloxacin between the sepsis group and the non-sepsis group (χ2=0.31,0.31,0.00,0.02,0.02,0.02,0.26, all P>0.05). Conclusions: Invasive non-typhoid Salmonella infection in children at Xiamen mainly occurred in infants younger than 3 years old.The main clinical manifestations are fever, abdominal pain and diarrhea. C-reactive protein can be served as the laboratory indicators for indicating sepsis. The third generation of cephalosporins is recommended as the first choice for treatment.

Bacterial antibiotic resistance among cancer inpatients in China: 2016-20.

BACKGROUND: The incidence of infections among cancer patients is as high as 23.2-33.2% in China. However, the lack of information and data on the number of antibiotics used by cancer patients is an obstacle to implementing antibiotic management plans. AIM: This study aimed to investigate bacterial infections and antibiotic resistance in Chinese cancer patients to provide a reference for the rational use of antibiotics. DESIGN: This was a 5-year retrospective study on the antibiotic resistance of cancer patients. METHODS: In this 5-year surveillance study, we collected bacterial and antibiotic resistance data from 20 provincial cancer diagnosis and treatment centers and three specialized cancer hospitals in China. We analyzed the resistance of common bacteria to antibiotics, compared to common clinical drug-resistant bacteria, evaluated the evolution of critical drug-resistant bacteria and conducted data analysis. FINDINGS: Between 2016 and 2020, 216 219 bacterial strains were clinically isolated. The resistance trend of Escherichia coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, cefotaxime, piperacillin/tazobactam and imipenem was relatively stable and did not significantly increase over time. The resistance of Pseudomonas aeruginosa strains to all antibiotics tested, including imipenem and meropenem, decreased over time. In contrast, the resistance of Acinetobacter baumannii strains to carbapenems increased from 4.7% to 14.7%. Methicillin-resistant Staphylococcus aureus (MRSA) significantly decreased from 65.2% in 2016 to 48.9% in 2020. CONCLUSIONS: The bacterial prevalence and antibiotic resistance rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, S. aureus and MRSA were significantly lower than the national average.

[Clinical validation of the 2020 diagnostic approach for pediatric autoimmune encephalitis in a single center].

Objective: To evaluate the value of the 2020 diagnostic criteria (Cellucci criteria) for pediatric autoimmune encephalitis (AE) in children with suspected AE in a single center. Methods: The clinical data of 121 children hospitalized at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2021, with a diagnosis of suspected AE, were retrospectively collected and analyzed. The children were divided into definite antibody-positive AE (dAPAE), probable antibody-negative AE (prANAE), possible AE (pAE) and non-AE groups according to the Chinese expert consensus and the Graus criteria. A new diagnosis was made according to the Cellucci criteria which was compared with the clinical diagnosis to evaluate the diagnostic value of the Cellucci criteria. The Mann-Whitney U test, Kruskal-Wallis test, and χ2 test were used to compare the differences among groups. The sensitivity and specificity were used to evaluate efficacy of the Cellucci criteria. Results: Among the 121 children, 72 were males and 49 were females, with an age of 10.3 (6.5, 14.0) years at disease onset. There were 99 cases diagnosed as AE according the clinical diagnosis (58 males and 41 females), of which 43 cases were diagnosed as dAPAE, 14 cases as prANAE and 42 cases as pAE, and the other 22 cases were not AE (14 males and 8 females). The top 2 initial symptoms in the 99 children with AE were seizures (53 cases, 53.5%) and abnormal mental behaviors (35 cases, 35.4%). And the most common symptoms during the course of the disease were abnormal mental behaviors (77 cases, 77.8%) and seizures (64 cases, 64.6%). There were statistically differences in the incidence of consciousness disorders, autonomic dysfunctions during the course of the disease and the length of hospitalization among the 4 groups (χ2=21.63, 13.74, H=22.60, all P<0.05). Ninety-six of the 121 children were tested for AE-related antibodies, of which 45 cases (46.9%) were antibody-positive. According to the Cellucci criteria, 42 cases were diagnosed as dAPAE, 34 cases as prANAE and 14 cases as pAE. Compared with the clinical diagnosis, the sensitivity of the Cellucci criteria for the diagnosis of the 3 types of AE were 93.02%, 92.86% and 87.88%, and the specificity were 96.23%, 74.39% and 86.36%, respectively. Conclusions: The Cellucci criteria has a high sensitivity and specificity for the diagnosis of pAE and dAPAE in the clinical management of children with suspected AE, while a high sensitivity but low specificity for the diagnosis of prANAE. Therefore, it is recommended to apply the Cellucci criteria selectively in clinical practice according to the actual situation, especially in the diagnosis of prANAE.

[Application of next-generation sequencing in detection of BRCA1/2 and homologous recombination repair pathway multi-genes germline mutation and correlation analysis].

Objective: To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population. Methods: This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test. Results: Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P=0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P=0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P=0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC). Conclusion: The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.

Acceleration of Brain Susceptibility-Weighted Imaging with Compressed Sensitivity Encoding: A Prospective Multicenter Study.

BACKGROUND AND PURPOSE: While three-dimensional susceptibility-weighted imaging has been widely suggested for intracranial vessel imaging, hemorrhage detection, and other neuro-diseases, its relatively long scan time has necessitated the clinical verification of recent progresses of fast imaging techniques. Our aim was to evaluate the effectiveness of brain SWI accelerated by compressed sensitivity encoding to identify the optimal acceleration factors for clinical practice. MATERIALS AND METHODS: Ninety-nine subjects, prospectively enrolled from 5 centers, underwent 8 brain SWI sequences: 5 different folds of compressed sensitivity encoding acceleration (CS2, CS4, CS6, CS8, and CS10), 2 different folds of sensitivity encoding acceleration (SF2 and SF4), and 1 without acceleration. Images were assessed quantitatively on both the SNR of the red nucleus and its contrast ratio to the CSF and, subjectively, with scoring on overall image quality; visibility of the substantia nigra-red nucleus, basilar artery, and internal cerebral vein; and diagnostic confidence of the cerebral microbleeds and other intracranial diseases. RESULTS: Compressed sensitivity encoding showed a promising ability to reduce the acquisition time (from 202 to 41 seconds) of SWI while increasing the acceleration factor from 2 to 10, though at the cost of decreasing the SNR, contrast ratio, and the scores of visual assessments. The visibility of the substantia nigra-red nucleus and internal cerebral vein became unacceptable in CS6 to CS10. The basilar artery was well-distinguished, and diseases including cerebral microbleeds, cavernous angiomas, intracranial gliomas, venous malformations, and subacute hemorrhage were well-diagnosed in all compressed sensitivity encoding sequences. CONCLUSIONS: Compressed sensitivity encoding factor 4 is recommended in routine practice. Compressed sensitivity encoding factor 10 is potentially a fast surrogate for distinguishing the basilar artery and detecting susceptibility-related abnormalities (eg, cerebral microbleeds, cavernous angiomas, gliomas, and venous malformation) at the sacrifice of visualization of the substantia nigra-red nucleus and internal cerebral vein.

Predicting survival and immune microenvironment in colorectal cancer: a STAT signaling-related signature.

BACKGROUND: Despite research advances, studies on predictive models of colorectal cancer (CRC) remain scarce and none have evaluated signal transducer and activator of transcription (STAT) signaling. AIM: To develop an effective prognostic signature for and evaluate its association with immune microenvironment. DESIGN: Comprehensive analysis based on The Cancer Genome Atlas and Gene Expression Omnibus databases with experimental validation. METHODS: Gene expression and clinical profiles of CRC patients were extracted from the databases. Differentially expressed genes with prognostic values were used to construct a signature. Immune cell infiltration and composition were further evaluated by TIMER, single-sample gene set enrichment and CIBERSORT analyses. The impact of the hub gene Caveolin-1 (CAV1) on cell proliferation, apoptosis, senescence and tumor angiogenesis was experimentally validated. RESULTS: The five-gene-based STAT signaling-related prognostic signature was significantly associated with CRC survival, and the nomogram was with improved prognostic efficacy than the conventional TNM stage. The STAT signaling-related signature was correlated with tumor immune microenvironment. CAV1 was further identified as the hub gene within the signature. CAV1 inhibits the proliferation and induces the apoptosis as well as senescence of CRC cells. In addition, the tumor angiogenesis of CRC can be suppressed by CAV1 overexpression. CONCLUSIONS: The STAT signaling-related signature effectively predicts the prognosis and regulates tumor immune microenvironment in CRC. Our study underscores the role of STAT regulator, CAV1, as an important tumor suppressor in CRC carcinogenesis. Modulating STAT and its regulators could be a promising strategy for CRC in clinical practice.

Protective effect of miR-146 against kidney injury in diabetic nephropathy rats through mediating the NF-κB signaling pathway.

The article "Protective effect of miR-146 against kidney injury in diabetic nephropathy rats through mediating the NF-κB signaling pathway", H.-Y. Yu, L.-F. Meng, X.-H. Lu, L.-H. Liu, X. Ci, Z. Zhuo, published in Eur Rev Med Pharmacol Sci 2020; 24 (6): 3215-3222-DOI: 10.26355/eurrev_202003_20688-PMID: 32271439, has been retracted by the authors due to some inaccuracies (some data cannot be repeated by further research). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20688.

Acceleration of Brain TOF-MRA with Compressed Sensitivity Encoding: A Multicenter Clinical Study.

BACKGROUND AND PURPOSE: The clinical practice of three-dimensional TOF-MRA, despite its capability in brain artery assessment, has been hampered by the relatively long scan time, while recent developments in fast imaging techniques with random undersampling has shed light on an improved balance between image quality and imaging speed. Our aim was to evaluate the effectiveness of TOF-MRA accelerated by compressed sensitivity encoding and to identify the optimal acceleration factors for routine clinical use. MATERIALS AND METHODS: One hundred subjects, enrolled at 5 centers, underwent 8 brain TOF-MRA sequences: 5 sequences using compressed sensitivity encoding with acceleration factors of 2, 4, 6, 8, and 10 (CS2, CS4, CS6, CS8, and CS10), 2 using sensitivity encoding with factors of 2 and 4 (SF2 and SF4), and 1 without acceleration as a reference sequence (RS). Five large arteries, 6 medium arteries, and 6 small arteries were evaluated quantitatively (reconstructed signal intensity, structural similarity, contrast ratio) and qualitatively (scores on arteries, artifacts, overall image quality, and diagnostic confidence for aneurysm and stenosis). Comparisons were performed among the 8 sequences. RESULTS: The quantitative measurements showed that the reconstructed signal intensities of the assessed arteries and the structural similarity consistently decreased as the compressed sensitivity encoding acceleration factor increased, and no significant difference was found for the contrast ratios in pair-wise comparisons among SF2, CS2, and CS4. Qualitative evaluations showed no significant difference in pair-wise comparisons among RS, SF2, and CS2 (P > .05). The visualization of all the assessed arteries was acceptable for CS2 and CS4, while 2 small arteries in images of CS6 were not reliably displayed, and the visualization of large arteries was acceptable in images of CS8 and CS10. CONCLUSIONS: CS4 is recommended for routine brain TOF-MRA with balanced image quality and acquisition time; CS6, for examinations when small arteries are not evaluated; and CS10, for fast visualization of large arteries.

XPG gene polymorphisms and glioma susceptibility: a two-centre case-control study.

Background: Glioma, the most common tumour in children next to leukaemia, is difficult to treat, with a poor prognosis and high recurrence rate. Xeroderma pigmentosum group G (XPG) plays a key role in the nucleotide excision repair pathway, which may modulate individual susceptibility to developing cancer. We hypothesized links between XPG variants and glioma in children.Methods: We tested our hypothesis in a study comparing 171 glioma cases with 228 age and sex matched controls, determining XPG polymorphisms rs2094258 C > T, rs751402 C > T, rs2296147 T > C, rs1047768 T > C, rs873601 G > A by standard molecular genetic methods.Results: rs2094258 C > T was associated with a decreased glioma risk, but carrying the rs1047768 C or rs873601 A allele brought an increased risk. Subjects carrying 5 risk genotypes had a significantly increased glioma risk at an adjusted odds ratio of 1.97 (95% confidence Interval 1.26-3.08)(p = 0.003) when compared with those carrying 0-4 risk genotypes. Furthermore, children with 5 risk genotypes had a higher glioma risk when aged >60 months, were more likely to be male, and with subtypes of astrocytic tumours, and low-grade clinical stage, when compared to those with 0-4 risk genotypes. Preliminary functional exploration suggested that rs2094258 is linked with the expression of its surrounding genes in the expression quantitative trait locus analysis.Conclusion: Certain variants of XPG are risk factors for paediatric glioma, and so may be useful in early diagnosis.

Transcriptome profiling analysis reveals distinct resistance response of cucumber leaves infected with powdery mildew.

Powdery mildew is the main disease affecting cucumber cultivation and causes severe economic loss. So far, research on cucumber resistance to powdery mildew has not yielded feasible solutions. This study selected two inbred cucumber lines, XY09-118 (resistant) and Q10 (susceptible) and investigated their responses to powdery mildew infection (harvested 24 and 48 h after inoculation) using RNA sequencing. More than 20,000 genes were detected in cucumber leaves both with and without powdery mildew infection at the above two time points. Among these, 5478 genes were identified as differently expressed genes (DEGs) between XY09-118 and Q10. Based on the databases GO and KEGG, the functions of DEGs were analysed. Moreover, the complex regulatory network for powdery mildew resistance was assessed, which involves plant hormone signal transduction, phenylpropanoid biosynthesis, plant-pathogen interaction and the MAPK signalling pathway. In particular, genes encoding WRKY, NAC and TCP were highlighted. In addition, genes involved in plant hormone biosynthesis, metabolism and signal transduction, pathogen resistance and abiotic stress response were analysed. Co-expression analysis indicated that the transcription factors correlated with plant hormone signal pathway and metabolism, defence and abiotic response. The expression of several genes was validated by qRT-PCR. The pathogen resistance regulatory network was identified by comparing resistant and susceptible inbred lines infected with powdery mildew. The transcriptome data provide novel insights into cucumber response to powdery mildew infection and the identified pathogen resistance genes will be highly useful for breeding efforts to enhance the resistance of cucumber to powdery mildew.

Protective effect of miR-146 against kidney injury in diabetic nephropathy rats through mediating the NF-κB signaling pathway.

OBJECTIVE: To study the protective effect of micro ribonucleic acid (miR)-146 against kidney injury in diabetic nephropathy (DN) rats through the nuclear factor-κB (NF-κB) signaling pathway. MATERIALS AND METHODS: In this experiment, 30 adult Sprague-Dawley rats with 5-6 weeks old and weighing 20-30 g were selected and randomly divided into control group (n=10), model group (n=10), and miR-146 Mimic group (n=10, DN rat model + miR-146 Mimic). The serum levels of creatinine (Cr) and blood urea nitrogen (BUN) in the three groups were detected using the full-automatic biochemical analyzer. The protein expression levels of phosphorylated-inhibitor of NF-κB (p-IκB), p-P65, P65, and Tubulin were detected via Western blotting. The messenger RNA (mRNA) of P65 was determined using quantitative Polymerase Chain Reaction (qPCR). Positive expression of p-IκB in tissues was determined using immunohistochemistry. Moreover, the contents of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were detected using the enzyme-linked immunosorbent assay (ELISA) kits. Finally, the apoptosis was detected through Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) dual-fluorescence labeling. RESULTS: The serum levels of Cr and BUN were significantly higher in the model group than those in the control group (p<0.01), while they were significantly lower in miR-146 Mimic group than those in the model group (p<0.05). The levels of p-IκB and p-P65/P65 significantly increased in the model group compared with those in the control group (p<0.01), while they remarkably declined in the miR-146 Mimic group compared with those in the model group (p<0.05). The results of qPCR showed that the mRNA level of P65 had no significant difference among the three groups (p>0.05). The immunohistochemical assay showed that the positive expression of p-IκB in tissues was consistent with those of the protein level as Western blotting revealed. The rats in the model group had evidently increased levels of TNF-α, IL-1ß, and IL-6 compared with the control group (p<0.01), while miR-146 Mimic group had evidently decreased levels of them compared with the model group (p<0.01). Finally, apoptosis was enhanced in the model group compared with that in the control group, while it was remarkably inhibited in the miR-146 Mimic group. CONCLUSIONS: MiR-146 can inhibit the NF-κB signaling pathway, lower the levels of TNF-α, IL-1ß, and IL-6, and reduce the apoptosis, thereby exerting a protective effect against kidney injury in DN.

A randomised controlled trial of stepwise sputum collection to increase yields of confirmed tuberculosis.

The proportion of bacteriologically confirmed tuberculosis (TB) in China has decreased far below the worldwide average. To investigate whether stepwise measures to ensure sputum quality can improve the rate of bacteriologically confirmed TB. We enrolled 980 adults with suspected TB from three counties in China during 2017 for this multicentre randomised controlled trial. Half the participants (n = 490) were randomly assigned to intervention groups that received instructions by a study nurse, and sputum induction, if necessary. In the remaining 490 patients, sputum samples were collected without observation. The primary outcome was the proportion of patients detected as bacteriologically positive on smear, culture or molecular assays (EasyNAT or Xpert). Bacteriological confirmation rates were significantly higher in the intervention than in the control group: overall (159/490 [32%] vs. 122/490 [25%]; P = 0.009); confirmation using smear (17% vs. 11%; P = 0.010); confirmation using culture (28% vs. 21%; P = 0.021); and confirmation using molecular assays (27% vs. 18%; P = 0.001). Most of the improvement was in patients who received instruction alone, while improvement was greatest in younger patients (adjusted odds ratio 1.27, 95%CI 1.05-1.53 per 10 years). If implemented effectively in resource-limited primary care clinics, our simple stepwise procedure combining instruction and sputum induction could increase the proportion of bacteriologically confirmed TB significantly. .

Influence of miR-34a on myocardial apoptosis in rats with acute myocardial infarction through the ERK1/2 pathway.

OBJECTIVE: To study the influence of micro-ribonucleic acid (miR)-34a on myocardial apoptosis in rats with acute myocardial infarction (AMI) through the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. MATERIALS AND METHODS: A total of 24 Sprague-Dawley (SD) rats were randomly divided into sham group (n=12) and model group (n=12). The heart was exposed in the sham group, while the AMI model was established in the model group. After sampling, the morphology of myocardial tissues was observed via hematoxylin-eosin (HE) staining, the expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were detected via immunohistochemistry, and the protein expression levels of ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) were detected via Western blotting. Moreover, the expression of miR-34a was detected via quantitative Polymerase Chain Reaction (qPCR), the apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and the myocardial injury indexes were detected using a fully-automatic biochemical analyzer. RESULTS: The morphology of myocardial tissues was normal with a complete structure in the sham group, while there was damage to myocardial tissues in different degrees in the model group. The immunohistochemical results revealed that the Bax expression was increased and the Bcl-2 expression was decreased in the model group compared with those in the sham group (p<0.05). The results of Western blotting showed that the protein expression levels of both ERK1/2 and p-ERK1/2 were significantly increased in the model group compared with those in the sham group (p<0.05). The qPCR results manifested that the expression of miR-34a in the model group markedly declined compared with that in the sham group (p<0.05). Besides, the TUNEL detection showed that the apoptosis rate in the model group was remarkably increased compared with that in the sham group (p<0.05), and the content of cardiac troponin T and creatine kinase isoenzyme in the model group was significantly higher than that in the sham group ((p<0.05). CONCLUSIONS: MiR-34a affects the apoptosis in AMI by regulating the ERK1/2 signaling pathway.

High BMI has no impact on the survival of Chinese patients with lower thoracic esophageal adenocarcinoma treated with curative esophagectomy: a propensity score-matched study.

Controversy still exists as to whether a high body mass index (BMI) has any impact on the long-term survival of esophageal cancer patients treated with curative esophagectomy. Therefore, we conducted this propensity score-matched (PSM) study to explore the prognostic value of high BMI in Chinese patients with lower thoracic esophageal adenocarcinoma for the first time. We retrospectively collected data of patients with lower thoracic esophageal adenocarcinoma who underwent curative esophagectomy in our department from January 2009 to December 2016. Patients were grouped into high BMI group (≥23 kg/m2) and normal BMI group (18.5-22.9 kg/m2) according to the Asian specific BMI cutoff value. Both Cox regression survival analysis and PSM analysis were applied. Finally, a total of 132 patients were included for analysis. Fifty-three patients were in the high BMI group while 79 patients were in the normal BMI group. There was no significant difference regarding age, gender, comorbidity, tumor differentiation, tumor site, lymphovascular invasion, or surgical approaches between the two groups. However, patients with a high BMI tended to have more stage III diseases but a lower rate of adjuvant therapy application than those with a normal BMI. For survival, there was no significant survival difference between patients with a high BMI and those with a normal BMI (5-year overall survival (OS): 40.8% vs. 48.1%; P = 0.398). In the multivariate analysis, high BMI was not found to be an independent prognostic factor (HR = 1.028, 95%CI: 0.621-1.667, P = 0.945). A total of 92 well-matched patients were included after PSM analysis. However, there was still no significant difference of survival between the two groups (5-year OS: 41.4% vs. 43.3%; P = 0.760). Therefore, high BMI has no impact on survival of Chinese patients with lower thoracic esophageal adenocarcinoma treated with curative esophagectomy.

Radiological follow-up results of untreated anterior disc displacement without reduction in adults.

The aim of this study was to assess the radiographic changes in untreated adults with bilateral anterior disc displacement without reduction. A cohort study was designed to compare the bone changes, effusion, disc configuration, and pseudo-disc changes on two magnetic resonance images obtained at least 24 months apart. Twenty-eight patients (22 female, six male) with a mean age of 33.1 years (range 20-57 years) were included. The mean interval between the initial visit and the follow-up visit was 36.2 months. At the initial visit, the frequencies of bone changes, effusion, disc deformation, and pseudo-disc changes were 51.79%, 35.71%, 100%, and 0%, respectively. At follow-up, the frequency of effusion had decreased significantly. The frequency of bone changes had increased significantly to 75%, but newly formed cortical bone was present in five condyles. All discs remained deformed. Pseudo-disc changes were detected in five joints. Over a long period of observation, there was a significant decrease in effusion and a significant increase in bone changes. However, some adaptive changes occurred.

Strain-induced mechanotransduction through primary cilia, extracellular ATP, purinergic calcium signaling, and ERK1/2 transactivates CITED2 and downregulates MMP-1 and MMP-13 gene expression in chondrocytes.

OBJECTIVE: To determine the strain-induced signaling pathways involved in regulating the transactivation of the transcription regulator Cbp/p300 Interacting Transactivator with ED-rich tail 2 (CITED2) and downstream targets in chondrocytes. METHODS: Primary human chondrocytes or C28/I2 chondrocytic cells were subjected to various strain regimes. C57BL/6 mice were subjected to treadmill running. Loss-of-function was carried out using siRNA or inhibitors specific for targeted molecules. mRNA levels were assayed by RT-qPCR, and proteins by western blotting, immunofluorescence, and/or immunohistochemical staining. CITED2 promoter activity was assayed in chondrocytes using wild-type or mutant constructs. RESULTS: Cyclic strain at 5%, 1 Hz induced CITED2 expression and suppressed expression of matrix metalloproteinase (MMP)-1 and -13 at the messenger RNA (mRNA) and protein levels in human chondrocytes. Abolishing primary cilia through knockdown of intraflagellar transport protein (IFT88) attenuated CITED2 gene expression and decreased protein levels. Similar effects were observed with inhibitors of extracellular adenosine triphosphate (ATP) or P2 purinergic receptors, or antagonists of Ca(2+) signaling. Knockdown of IFT88 in articular chondrocytes in vivo diminished treadmill induced-CITED2 expression and upregulated MMPs. Knockdown of hypoxia-inducible factor (HIF)1α, specificity protein 1 (Sp1), or deletion of the shear stress response element (SSRE) in the CITED2 promoter limited cyclic strain-induced transactivation of CITED2. However, the strain induced-transactivation of CITED2 was abolished only on knockdown of HIF1α, Sp1, and SSRE or by loss-of-function of IFT88 or extracellular-signal-regulated kinases (ERK)1/2. CONCLUSIONS: CITED2 transactivation is a critical event in signaling generated by strain and transduced by primary cilia, extracellular ATP, P2 purinergic receptors, and Ca(2+) signaling. Strain-induced CITED2 transactivation requires HIF1α, Sp1, and an intact SSRE and leads to the downregulation of MMPs such as MMP-1 and MMP-13.

Zinc glycine chelate absorption characteristics in Sprague Dawley rat.

This study was conducted to investigate absorption characteristics of zinc glycine chelate (Zn-Gly) by evaluating tissues zinc status and the expression of zinc transporters in rats. A total of 24 male rats were randomly allocated to three treatments and administered either saline or 35 mg Zn/kg body weight from zinc sulphate (ZnSO4 ) or Zn-Gly by feeding tube separately. Four rats per group were slaughtered and tissues were collected at 2 and 6 h after gavage respectively. Our data showed that Zn-Gly did more effectively in increasing (p < 0.05) serum zinc levels, and the activities of serum and liver alkaline phosphatase (ALP) and liver Cu/Zn superoxide dismutase (Cu/Zn SOD) at 2 and 6 h. By 2 h after the zinc load, the mRNA and protein abundance of intestinal metallothionein1 (MT1) and zinc transporter SLC30A1 (ZnT1) were higher (p < 0.05), and zinc transporter SLC39A4 (Zip4) lower (p < 0.05) in ZnSO4 compared to other groups. Zinc transporter SLC39A5 (Zip5) mRNA expression was not zinc responsive, but Zip5 protein abundance was remarkably (p < 0.05) increased in ZnSO4 2 h later. Overall, our results indicated that in short-term periods, Zn-Gly was more effective in improving body zinc status than ZnSO4 , and ZnSO4 did more efficiently on the regulation of zinc transporters in small intestine.

Prenatal diagnosis based on HPRT1 gene mutation in a Lesch-Nyhan family.

We explored the feasibility of applying gene diagnosis in prenatal diagnosis by analysis of hypoxanthine-guanine phosphoribosyltransferase-1 (HPRT1) gene mutation in a Chinese Lesch-Nyhan family. A homozygous mutation of p.R170X (c.508C＞T) in HPRT1 gene was detected in the proband, and a heterozygous mutation of p.R170X was detected in his mother. This mutation failed to be found in the 50 unrelated healthy individuals. Prenatal diagnosis indicated that the foetus was male and also carried p.R170X (c.508C＞T) mutation, same as the proband. Parents of the foetus decided termination of pregnancy, and the result of gene analysis for the aborted tissue was consistent with that of prenatal diagnosis. We can see that Lesch-Nyhan syndrome (LNS) is caused by non-sense mutation p.R170X（c.508C＞T）in HPRT1 gene in this family. Prenatal gene diagnosis is a valid strategy to prevent LNS because it can avoid the birth of LNS foetuses.